SOLID PHARMACEUTICAL COMPOSITION

Abstract

Claim 1: A solid dosage form characterized in that it comprises a compound represented by formula (1), or a pharmaceutically acceptable salt thereof, and one or more compounds selected from the group consisting of an alkali metal chloride, an organic acid, a polyhydric alcohol ester, and a fatty acid ester. Claim 10: A solid dosage form characterized in that it comprises a compound represented by formula (1), a pharmaceutically acceptable salt thereof, and a cellulose-based polymer, provided that the solid dosage form does not contain a cellulose-based polymer in a coating layer. Claim 16: The solid dosage form according to any one of claims 1 to 15, characterized in that it contains a compound of 10 mg, 20 mg, 40 mg, or 80 mg represented by formula (1).

Description

either 26839 Soda dosage form with excellent stability TECHNICAL FIELD The present invention relates to a polycyclic polymer containing PWd°amaltitol and mannitol, as an alcohol of a water-soluble polymer and myr acid, promellose com° uiuoie, and light anhydrous silicic acid and a non-irradiative substance and the co as a BACKGROUND (commercial: Flumadine) that caused ZTZZZ ΓT -Ions of patient reports 7 “JaPÓ· “ winters, and Influenza presents η,ο'^^^θG^οΙΧ^,όTΤθ23 As drugs against the infection, commercial: Symmetrel) and rimantadine (inhibit the virus's uncoating process and inhibit a novel mechanism. Given that a cap-dependent endonuclease that is a derivative of the Hp iainri»p'qUe is an en2|ma '°—eZZ czχ-- -·yendonuclease is suitable for a Page 1 of 50 influenza. As a cap-dependent endonuclease inhibitor compound, a compound represented by the following Formula (II) is described in patent literature 1, and this compound is useful as a compound having antiviral activity, in particular, having influenza virus proliferation inhibitory activity. [Formula 1] OH O When the compound represented by Formula (II) is administered (e.g., orally) to a living organism, it is necessary to provide a compound that is more efficiently absorbed into the body in order to exhibit a high pharmacological effect and shorten the duration of influenza illness. For these purposes, a compound represented by the following Formula (I), i.e., a prodrug of the compound represented by Formula (II), is provided. The compound represented by the following Formula (I) is also disclosed in patent literature 1. [Formula 2] However, patent literature 1 does not disclose a specific preparation of the compound represented by Formula (I). Influenza is a particularly significant disease in high-risk populations, such as children and the elderly. In particular, among the currently available anti-influenza drugs, a pediatric preparation2^ Page 2 of 50 present a fine granule flavor, a tablet^T^^ '° --a stability test tetZ,θ' ~ internal use can be suspended ””Pediatric Preparation for children, and a drug“θ θ' '° —even suspensibility in water - ·-:-Az·.. Related substances lueon H= ,Small amount<*θ also have good suspensibility^Twater and fluidT'''^ Patent literature 9 to δ one of the patent literatures 2 to 4 ΓfOrmUlacl° described in each ......™. „” ;·'” - “· dy mantol. A compound used in the represented by fLI7^nT' ' ​​muia (t) in the chemical structure, and it is not clear whether the one in patent literature 5 results in an excellent PREVIOUS ART DOCUMENT [PATENT LITERATURE] patent literature 5 formulation described suspensibility in [Literature [Literature 2008-07420 [Patent literature 1) International Publication No. WO2016 / 175224 Patent 2J Japanese patent open to public inspection N. patent 3) Japanese patent Page 3 of 50 2016-79102 [Patent Literature 4J National and International Publication No. 2001-512433] [Patent Literature 5J National and International Publication No. 2014-534215 Patent Application SUMMARY OF THE INVENTION TECHNICAL PROBLEM a dosage form An object of the present invention is to find a solid having excellent stability of a compound of Formula (I) and also having excellent suspensibility in water. problems that the invention must solve To solve the problems described above, the inventors of the present invention carried out exhaustive studies which resulted in the finding that the stability, the spreadability of a preparation in water, and the flowability of the preparation are improved by the use of a metal chloride, an organic acid, a polyhydric alcohol ester, and a fatty acid ester as a stabilizing substance, a sugar alcohol and / or a sugar, a water-soluble polymer, and an inorganic substance, thus achieving the present invention. Hereinafter, a preparation obtained by means of the present invention is referred to, in some cases, as the preparation and, in some cases, as the present preparation. Specifically, the present invention relates to the following: ( ) A solid dosage form comprising a compound represented by the following Formula (I); [Formula 3] or more° / rSal daeStS Acceptable from the Point of View fa™^ulico, and one an acid of the 9rUp° that consists of an alkali metal chloride, or organic, a polyhydric alcohol ester.jdniéstsqOeSdifibl^ISgíjfNPI Page 4 of 50 (2) the solid dosage form according to (1) above solid dosage form comprises an alkali metal chloride, and the alkali metal is sodium chloride and / or potassium chloride; (3) the solid dosage form according to (1) above, solid dosage form comprises an organic acid, and the acid is ascorbic acid and / or fumaric acid; where the chloride where organic of the is where the (4) solid dosage form according to (1) above, solid dosage form comprises a polyhydric alcohol ester.' and the polyhydric alcohol ester is one or more sections of, group consisting of Miglyol, methyl citrate and polyoxyethylene sorbitan monooleate; (5) the solid dosage form according to (1) above, wherein the solid dosage form comprises a fatty acid ester, and the fatty acid ester is acetate; (6) the solid dosage form according to any of (1) to (5) above, further comprising a sugar alcohol and / or a sugar; (7) the form of=, . , „d°SiS solid according to θοη (6) above, wherein the sugar alcohol and / or sugar is one or more selected from the group that “ T, 'Γ133·syrup d6 a,midÓda-°- hydrogenated (mannitol), mannitol, x.btol, erythritol, sorbitol, lactose, sucrose, fructose, maltose, purified white sugar and trehalose; (8) the solid dosage form according to any of (1) to (7) above, further comprising a water-soluble polymer; (9) the solid dosage form according to (8) above, wherein the water-soluble polymer is a cellulose-based polymer; Formula G)-A C°mprende Unitpuesto de-la.[Formula 4] or a salt of this acceptable from the Page 5 of 50 cellulose-based polymer, provided that the solid dosage form does not contain cellulose-based polymer in a coating layer; (11) the solid dosage form according to (9) or (10) above, wherein the cellulose-based polymer is one or more selected from the group consisting of hypromellose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, carboxymethyl ethylcellulose, hypromellose phthalate, and hydroxypropyl methylcellulose acetate succinate; (12) the solid dosage form according to (11) above, wherein the cellulose-based polymer is hypromellose; (13) the solid dosage form according to any of (1) to (12) above, which also comprises an inorganic substance, provided that the solid dosage form does not contain an inorganic substance in a coating layer; . (14) the solid dosage form according to (13) above, wherein the inorganic substance is one or more selected from the group consisting of hydrated silicon dioxide, light anhydrous silicic acid, and talc; and (15) the solid dosage form according to any of (1) to (14) wherein the release rate of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof is 80% or more after 15 minutes from the start of the dissolution test in the dissolution test method (paddle method) indicated in the 17th edition of the Japanese Pharmacopoeia. (16) the solid dosage form according to any of (1) to (15) containing 10 mg, 20 mg, 40 mg or 80 mg of compound represented by the following Formula (I): [Formula 5] (17) the solid dosage form according to any of (1) to (16) that is a granule or an oral suspension in powder form.-2019-62947435-APN-ANP#INPI Page 6 of 50 ADVANTAGEOUS EFFECTS OF THE INVENTION A preparation containing one or more stabilizing substances selected from the group consisting of an alkali metal chloride, an organic acid, a polyhydric alcohol ester and a fatty acid ester, a sugar alcohol and / or a sugar, a water-soluble polymer and an inorganic substance achieves a reduction in the amount of related substances of a polycyclic pyridone compound and improves the flowability of the preparation and the suspensibility of the preparation in water. BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] Figure 1 shows a powder X-ray diffraction pattern of the crystal of the compound represented by Formula (I). [Figure 2] Figure 2 shows the dissolution profile of the compound represented by Formula (I) at the start of a temporary storage test and after an indicated period of time from the start of the temporary storage test. DESCRIPTION OF THE FORMS OF REALIZATION The active ingredient of the present preparation is a compound represented by the following Formula (I) or a pharmaceutically acceptable salt thereof: [Formula 6] A method for producing the compound represented by Formula (I) or the salt thereof acceptable from a pharmaceutical point of view is disclosed in Patent Literature 1. The compound represented by Formula (I) or its pharmaceutically acceptable salt is converted into a compound represented by Formula (II) in a living organism and has an inhibitory action on the cap-dependent endonuclease. Consequently, the compound represented by Formula (I) or lalí'alGde-éWVáSfeiátSbfállá^Wfel Page 7 of 50 From a pharmaceutical point of view, it is useful as an agent to treat and / or prevent influenza. The compound represented by Formula (I) or a pharmaceutically acceptable salt thereof is useful for treating symptoms and / or diseases induced by the influenza virus. It is useful for the treatment and / or prevention and symptomatic improvement of, for example, cold-like symptoms accompanied by fever, chills, headache, muscle pain, and general malaise; symptoms of respiratory tract inflammation, such as sore throat, runny nose, nasal congestion, cough, and phlegm; gastrointestinal symptoms, such as stomach pain, vomiting, and diarrhea; and complications related to secondary infections, such as acute encephalopathy and pneumonia. In other words, the compound used in the present invention is useful for the treatment and / or prevention of infectious diseases caused by the influenza virus. The compound represented by Formula (I) or a pharmaceutically acceptable salt thereof is useful for shortening the duration of influenza. The duration of influenza can be shortened, for example, by approximately 20 to 40 hours or by approximately 25 to 30 hours. Specifically, it can shorten the time required to relieve symptoms such as cough, sore throat, headache, nasal congestion, low-grade fever or chills, muscle or joint pain, and fatigue. It is particularly useful for shortening the time required to relieve symptoms of nasal congestion, muscle or joint pain, fatigue, low-grade fever or chills, and headache. Furthermore, it is useful for shortening the time required to relieve symptoms of nasal congestion and muscle or joint pain. The compound represented by Formula (I) or its pharmaceutically acceptable salt is useful as a drug. The compound represented by Formula (I) or its pharmaceutically acceptable salt is a prodrug that has the advantages of high oral absorption, good bioavailability and clearance, and high distribution in the lungs, and therefore, it can be an excellent drug. The compound represented by Formula (I) or its pharmaceutically acceptable salt exhibits high metabolic stability and oral absorption, as well as good bioavailability and clearance. Furthermore, the compound represented by Formula (I) or its salt Page 8 of 50 From a pharmaceutical standpoint, the compound is widely distributed in the lungs and has a prolonged half-life. Furthermore, the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof is advantageous because it has a high protein-free binding rate and low CYP inhibition or hERG channel inhibition, exhibits CPE inhibitory activity (cytopathic effect), and / or is negative in the phototoxicity test, Ames test, and genotoxicity test, or has no toxicity that produces liver damage or similar effects. Consequently, a pharmaceutical composition of the compound used in the present invention may be an excellent drug. A dose of the compound represented by Formula (I) or its salt, acceptable from a pharmaceutical standpoint, varies according to the method of administration, the patient's age, weight, and condition, and the type of disease. When oral administration is used, a dose of, in general, about 0.05 mg to 3000 mg, preferably about 0.1 mg to 1000 mg, and even more preferably about 10 mg to 80 mg, is administered to an adult daily, if necessary in divided doses. When parenteral administration is used, a dose of about 0.01 mg to 1000 mg, preferably about 0.05 mg to 500 mg, or even more preferably about 1 mg to 80 mg, is administered to an adult daily. This dose may be administered as a single dose or in divided doses several times a day. Specifically, the content of the compound represented by Formula (I) or the salt thereof acceptable from a pharmaceutical point of view is 10 mg, 20 mg, 40 mg or 80 mg.In this case, 10 mg represents the range of 9.0 to 11.0 mg, preferably 9.5 to 10.5 mg, 20 mg represents the range of 18.0 to 22.0 mg, preferably 19.0 to 21.0 mg, 40 mg represents the range of 36.0 to 44.0 mg, preferably 38.0 to 42.0 mg, 80 mg represents the range of 72.0 to 88.0 mg, preferably 76.0 to 84.0 mg. The compound represented by Formula (I) or a pharmaceutically acceptable salt thereof may be used in combination with another drug or similar drug (hereafter referred to as a concomitant drug) to enhance the action of the compound or reduce the dosage of the compound. To treat influenza, for example, it may be used in combination with a neuraminidase inhibitor (such as oseltpiKktA6XainaMiViP,NpteimWi}VR-I or Page 9 of 50 Inavir), an RNA-dependent RNA polymerase inhibitor (such as favipiravir), an M2 protein inhibitor (such as amantadine), a PB2 cap-binding inhibitor (such as VX-787), an anti-HA antibody (such as MHAA4549A), or an immune agonist (such as nitazoxanide). In this case, the administration periods of the compound and the concomitant drug used in the present invention are not limited, and they may be administered simultaneously to a single recipient or at different times. Furthermore, the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof and the concomitant drug may be administered in the form of two or more preparations containing, respectively, active ingredients, or may be administered in the form of a single preparation containing all the active ingredients. The dosage of the concomitant drug may be appropriately selected based on a clinically used dose. Likewise, a pharmaceutically acceptable mixing ratio between the compound represented by Formula (I) or its salt and the concomitant drug may be appropriately selected based on the recipient, route of administration, target disease, symptoms, or a combination thereof. When the recipient is, for example, a human, the concomitant drug may be used in an amount of 0.01 to 100 parts by weight based on 1 part by weight of the compound represented by Formula (I) or its pharmaceutically acceptable salt. The compound represented by Formula (I) or the pharmaceutically acceptable salt thereof may be a drug with a lower probability of producing adverse reactions, since it is a virus-specific enzyme that has high inhibitory activity against the cap-dependent endonuclease and, therefore, has high selectivity and similar effects. A method for specifying a compound represented by Formula (I) or a crystal thereof, or a compound represented by Formula (II), will now be described. The numerical values ​​mentioned for ranges in this and the appended claims are approximate values. Page 10 of 50 On the contrary. The variation in numerical values ​​is produced by factors such as device calibration, device error, an impurity in a substance, crystal size, and sample size. As used herein, the term crystal means a cyclic, anisotropic structure that arises from the regular alignment of atoms, ions, molecules, or similar components that constitute a solid. A crystal form and degree of crystallinity can be measured by any of several techniques, including, for example, powder X-ray diffraction analysis, moisture adsorption / desorption analysis, differential scanning calorimetry, simultaneous thermogravimetric analysis, colorimetric analysis of solution, and solubility characteristics. NMR analysis of a compound was performed at 300 MHz using DMSO-d6 and CDCI3. Measurement of an X-ray diffraction pattern of powder In accordance with the powder X-ray diffraction method described in the General Tests of the Japanese Pharmacopoeia, the crystal obtained in each example was subjected to powder X-ray diffraction analysis. The analysis conditions are as follows: (Apparatus) MiniFlex 600, manufactured by Rigaku Corporation (Operating Method) Detector: high-speed one-dimensional detector (D / Tec Ultra 2) and variable blade edge Measurement method: reflection method Light source type: Cu Wavelength: CuKa radiation Tube current: 15 mA Tube voltage: 40 kV Sample board: zero-bottom silicon support X-ray incidence angle (Θ): 4 - 40°, sampling width: 0.02° In general, an error of ±0.2° occurs in the diffraction angle (20) in powder X-ray diffraction, and therefore the diffraction angle value spans values ​​in the range of approximately ±0.2°. Accordingly, the present invention utilizes Page 11 of 50 equal in the diffraction angle at a peak in the powder X-ray diffraction, but also an equal crystal in the diffraction angle at a peak with an error of about ±0.2°. A pharmaceutically acceptable content of the compound represented by Formula (I) or its salt in the present preparation is 0.1 to 10% by weight, preferably 0.5 to 8% by weight and, more preferably, 1 to 4% by weight depending on the total amount of the preparation. This preparation may contain a stabilizing substance. The stabilizing substance may be one described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan, and in particular, one capable of stabilizing the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof during temporary storage. The stabilizing substance can be any substance that reduces the amount of related substances, particularly the compound represented by Formula (II), and specific examples include an alkali metal chloride, an organic acid, a polyhydric alcohol ester, and a fatty acid ester. An alkali metal chloride is an inorganic compound represented by the chemical formula MX, where M is an alkali metal and X is chlorine. Specific examples include sodium chloride and potassium chloride, of which sodium chloride is preferred. An organic acid is an organic compound that has a carboxyl group (carboxylic acid), a sulfo group (sulfonic acid), or a hydroxyl, thiol, or enol group as a characteristic group. Specific examples include formic acid, oxalic acid, acetic acid, citric acid, ascorbic acid, and fumaric acid, with ascorbic acid being the most preferred and fumaric acid the most preferred. A polyhydric alcohol ester refers to a form of ester of an alcohol that has two or more hydroxyl groups in the molecule, and the hydroxyl groups are attached to separate carbon atoms in the polyhydric alcohol. Specific examples include Miglyol9(um7iigiÍ£éPMoXIdB#Iád?tio Page 12 of 50 medium-chain fatty acid), triethyl citrate and polyoxyethylene sorbitan monooleate, of which Miglyol is preferred. A fatty acid ester is a compound in which a fatty acid carboxyl group is linked via an ester to an alcohol. Specific examples include tracetin (glyceryl triacetate), a fatty acid ester of glycerol, acylglycerol, a monoglyceride derivative, and a fatty acid ester of polyglycerol, of which tracetin is preferred. The stabilizing substance in this preparation can be mixed into the preparation or can coat a surface of the preparation, and preferably, the stabilizing substance is mixed into the preparation. When the stabilizing substance is mixed into the preparation, it improves the stability of the compound represented by Formula (I) contained in the preparation and can reduce the amount of related substances, in particular, the compound represented by Formula (II). The stabilizing substance content of this preparation is 0.01 to 10% by weight, preferably 0.05 to 7.5% by weight, and more preferably 0.1 to 5% by weight, depending on the total quantity of the preparation. When the content is lower, the quantity of related substances may increase. This preparation may contain an excipient. Any excipient described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used as an excipient. Any excipient that provides good suspension of the preparation in water and low adhesion of the preparation to a container, as well as a high yield of fine granules and low bulk density, is preferred. Specific examples include a sugar alcohol and a sugar. Sugar alcohol is a carbohydrate under the food labeling standards notified by the Consumer Affairs Agency of the Government of Japan, and is a type of sugar produced by the reduction of a carbonyl group from an aldose or ketose. Specific examples include isomalt, erythritol, D-mannitol, xylitol, sorbitol, hydrogenated maltose starch syrup (maltitol), lactitol, and oligosaccharide alcohol, of which D-mannitol and hydrogenated maltose starch syrup (maltitol) are preferred. IF-2019-6294743 5-APN-ANP#INPI Page 13 of 50 : ; ,*·· “ ···— -........... Government of Japan and the,C°a™¡dor of! disaccharides, plus pe I om7 θ^''005—trites and sucrose, fructosX'°*™· purified, white orám.lr 'SOnier'Zada',arabe· anhydrous white sugar, and granules eZ l'co *PU^· '°*™ z-~ ·——· ........ of sugar and a sugar can be combined with an alcohol or sugar alcohol, or the ratio of the alcohol mixture to combine can be any type and suspensibility of the preparation in water container and offer high yield The type and ratio of sugar to be used in the mixture should improve the low bulk density. Examples include purified white sugar and syrup (maltitol), purified white sugar and a fine granule of the preparation, and specific combinations of hydrogenated maltose starch. Hydrogenated maltose (maltitol) and D-mannitol of the hydrogenated maltose starch syrup (maltitol) of the mixture is from gg:1 to 1;98_with preference 80.*20 to ?n*fin \t ~ ..20-80 and'with Particular preference 7ς·ος in terms of weight ratio. Plus and D-mannitol. At 10:90, starch is preferred. The ratio with greater than 25:75 in hydrogenated maltose starch (ZaltltónZZ'n 'θ' 'θ'30™ θ'™ ,η.,π . (maltitoi) with respect to D-mannitol is 30:70 to 50:50. an excipient other than a This preparation may contain sugar alcohol or a sugar such as oligosaccharides, dextrin, dehydrated polysaccharide, crystalline cellulose, desimidigested cellulose, glucose, aminoethylsulfonic acid, sodium chloride, glycine, calcium gluconate, potassium hydrogen carbonate, tartaric acid, calcium tartrate, povidone, and polyethylcellulose. 4000. macrogol 6000, anhydrous citric acid. Page 14 of 50 sodium, potassium dihydrogen phosphate, sodium dihydrogen phosphate, laxative, alginic acid, sodium carboxymethylcellulose, hydrated silicon dioxide, crospovidone, calcium glycerophosphate, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, synthetic aluminum silicate, flour, wheat starch, wheat germ, rice flour, rice starch, cellulose acetate phthalate, titanium oxide, magnesium oxide, dihydroxyaluminum aminoacetate, tribasic calcium phosphate, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, natural aluminum silicate, corn starch, granulated corn starch, potato starch, hydroxypropylcellulose, hydroxypropyl starch, anhydrous calcium hydrogen phosphate, granulated anhydrous calcium hydrogen phosphate, and calcium dihydrogen phosphatewhich correspond to a carbohydrate according to the food labeling standards notified by the Consumer Affairs Agency of the Government of Japan. The excipient content in this preparation is 1 to 99.5% by weight, preferably 5 to 99% by weight, and more preferably 10 to 98.5% by weight, depending on the total quantity of the preparation. Higher excipient content may prevent the mixing of other components. Lower excipient content may affect the appearance of the preparation. This preparation is suspended in water, and the suspension can be ingested. This method of administration is particularly suitable for children. However, it is difficult to suspend this preparation without a suspending agent. Therefore, a suspending agent may be mixed into this preparation. Any suspending agent described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used.Specific examples include cellulose-based polymers such as carmellose, sodium carmellose, crystalline cellulose / sodium carmellose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose), methylcellulose, carboxymethyl ethylcellulose, hydroxyethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and a mixture of fumaric acid / stearic acid / polyvinyl acetal diethylamine acetate / hydroxypropyl methyl. IF-2019-6294743 5-APN-ANP#INPI| 5 Page 15 of 50 cellulose; polymers based on polymers such as a dispersion of ethyl acrylate / methyl methacrylate copolymers, an aminoalkyl methacrylate copolymer, a methacrylic acid copolymer, a 2-methyl-5-vinylpyridin methyl acrylate / methacrylic acid copolymer, a dry methacrylic acid copolymer, and a dimethyl aminoethyl methacrylate / methyl methacrylate copolymer; vinyl-based polymers such as polyvinylpyrrolidone, crospovidone, a carboxyvinyl polymer, polyvinyl acetal diethylamino acetate, polyvinyl alcohol, a polyvinyl alcohol / methyl methacrylate / acrylic acid polymer, and a polyvinyl alcohol copolymer;Sodium alginate, carrageenan, a carboxyvinyl polymer, a dry aluminum hydroxide gel, xanthan gum, magnesium aluminum silicate, sodium polyphosphate, macrogol 4000, and macrogol 6000, of which carmellose, sodium carmellose, crystalline cellulose / sodium carmellose, hydroxypropylcellulose, hypromellose, and polyvinylpyrrolidone are preferred, with hypromellose being the most preferred. The suspending agent also functions as a dispersant that disperses the present preparation in water. However, when forming a coating layer on the solid dosage form, the solid dosage form does not contain cellulose-based polymers in the coating layer. The suspending agent content in this preparation is 0.01 to 10% by weight, preferably 0.05 to 7.5% by weight, and more preferably 0.1 to 5% by weight, depending on the total amount of the preparation. At higher concentrations, the preparation may foam in water. At lower concentrations, the preparation may not be able to be suspended in water. A fluidizing agent may be mixed into the present preparation to improve its flowability. Since the amount of impurities or related substances may increase depending on the fluidizing agent, it is necessary to select a fluidizing agent such that the amount of impurities or related substances does not increase. Any fluidizing agent described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used as the fluidizing agent, and typically, an inorganic substance, a fatty acid, or a salt thereof is usually selected. Specific examples include light anhydrous silicic acid, hydrated silicon dioxide, stearic acid, IF-2019-6294743 5-APN-ANP#INPI Page 16 of 50 and talc, among which it is possible that at the time of preparation for the selection of magnesium stearate, calcium stearate, they prefer light anhydrous silicic acid and hydrated silicon dioxide and dCOZ Γ θ'áCid° θ'0''0 anhydrous° 'iVÍan0·However, in the case of a coating layer in the solid dosage form, the dosage form does not contain inorganic substance in the coating layer The fluidizing agent content of this preparation is 0.0% by weight, preferably 0.05 to 7.5% by weight, depending on the total amount of the preparation. When the content is higher, it is possible that the amount of related substances will increase. When the content is lower, the preparation will not fluidize and will become an obstacle to preparation. A lubricant can be mixed into the present to improve the lubricity of the preparation. An indicator for meiZn'?5“án9Ul°reP0S°'7 Umen°r ángul° «θ Poso means better flowability. Any lubricant described in the Japanese Pharmacopoeia in the EsOpecif7aCeU“CO Ε”RIPPθ5 Japanese pharmaceuticals, and may contain any of the additives in Japanese pharmaceuticals. ...to be used as the lubricant, and normally, an inorganic substance, a 'fatty', or a salt thereof, is usually selected. Specific ones include light anhydrous silicic acid, silicon dioxide, sucrose fatty acid, stearyl alcohol, magnesium stearate, calcium stearate, stearyl fumarate, among which light anhydrous silicic acid, hydrated silicon dioxide, and calcium stearate are preferred, and calcium stearate is preferred even more. However, in the case where the lubricant is an inorganic substance and in the case of forming a coating layer in solid dosage form, the dosage form does not contain an inorganic substance in the coating layer. The lubricant content in the present preparation is 0.001 to 1% by weight, preferably 0.005 to 0.75% sn 01 to 0 5 « / »n „P°y'with greater preference, the content of the preparation increases when the quantity of related substances increases. When the content is lower, the preparation does not flow and becomes an obstacle at the time of production IF-2013-62947435 -APN-ANP#INPI Examples: hydrated, stearic, sodium, and Page 17 of 50 A flavoring agent may be mixed into this preparation to correct the taste of an unpleasant-tasting drug (e.g., bitter) as an additive. Any flavoring agent described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used.Specific examples include ascorbic acid, aspartic acid, aspartame, sucralose, glycine, sodium chloride, magnesium chloride, hydrochloric acid, dilute hydrochloric acid, citric acid and a salt thereof, anhydrous citric acid, L-glutamic acid and a salt thereof, succinic acid and a salt thereof, acetic acid, tartaric acid and a salt thereof, sodium bicarbonate, fumaric acid and a salt thereof, malic acid and a salt thereof, glacial acetic acid, disodium inosinate, honey, hydrogenated maltose starch syrup (maltitol), and powdered glycyrrhiza, among which sodium chloride is preferred. The flavoring agent content in this preparation is 0.01 to 10% by weight, preferably 0.05 to 7.5% by weight, and more preferably 0.1 to 5% by weight, depending on the total quantity of the preparation. When the quantity is higher or lower, the preparation may have an unpleasant taste when ingested. This preparation may contain a binder. Any binder described in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used as a binder. Specific examples include hydroxypropylcellulose, corn starch, pregelatinized starch, partially pregelatinized starch, gum arabic, powdered gum arabic, gelatin, agar, dextrin, pullulan, polyvinylpyrrolidone, polyvinyl alcohol, crystalline cellulose, methyl cellulose, ethyl cellulose, carboxymethyl ethyl cellulose, carmellose, sodium carmellose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropylcellulose, and hypromellose, of which polyvinylpyrrolidone is preferred. The binder content in this preparation is 0.1 to 20% by weight, preferably 0.25 to 15% by weight, and more preferably 0.5 to 10% by weight, depending on the total quantity of the preparation. Higher contents may result in an excessively large particle size. Lower contents may result in a lower particle size. IF-2019-6294743 5-APN-ANP#INP^8 Page 18 of 50 If the particle size of the preparation becomes too small, the present preparation may contain a disintegrant. Any disintegrant is described in the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Standards and Regulations for the Use of Food Additives, and the specific examples include sodium scarmellose. Crospovidone, calcium carboxymethyl starch, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose. 0.5 to 20% by weight, preferably 0.75 to 15% by weight and, with greater preference, 1 to 10% by weight depending on the total amount of the preparation This preparation may contain a polymer. It may be used as any polymer described in the Japanese Pharmaceutical Pharmacopoeia, the Japanese Pharmaceutical Excipients, and the specifications and standards for use of food additives in Japan. Specific examples include cellulose-based polymers such as hydroxypromellose (hydroxypropyl methylcellulose), polyvinyl alcohol, ethyl cellulose, carboxymethyl cellulose, carmellose, sodium carmellose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose acetate succinate, hydroxypropyl methyl cellulose acetate, and a mixture of fumaric acid / stearic acid / polyvinyl alcohol. acetal diethylamino acetate / hydroxypropi, co ' r aPOLYMARS 3 ACRYLIC° BASE', a'as« disperslX of methacHIate5up6 aCn,at° / methmethacrylate°.a copolymer of aminoalkyl methacrylate, a copolymer of methacrylic acid, a copolymer of 2-methyl-5-methyl methacrylate; vinyl-based polymers, such as polyvinylpyrrolidone, crospovidone, a xylene glycol, a polyvinyl alcohol / methyl methacrylate / hydroyl acid polymer, and a copolymer of polyvinyl alcohol and carnauba wax, stearyl alcohol, acetate gum, among which hypromellose (hydroxypropyl methylcellulose) is preferred. This preparation may contain a colorant. Any colorant described in the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Excipients, and the specifications and usage guidelines may be used. -------- . 19 Page 19 of 50 Specific examples include iron oxide, tar tincture, and natural tincture. Examples of iron oxide include ferric oxide, yellow iron oxide, yellow ferric oxide, and black iron oxide. Examples of tar tincture include Food Grade Yellow Aluminum Lake No. 4, Food Grade Blue Aluminum Lake No. 1, Food Grade Red Aluminum Lake No. 3, Food Grade Blue No. 1, Food Grade Blue No. 2, Food Grade Yellow No. 4, Food Grade Yellow No. 5, Food Grade Red No. 102, Food Grade Red No. 2, and Food Grade Red No. 3. Examples of natural tincture include turmeric extract, β-carotene, carotene solution, sodium copper chlorophyllin, copper chlorophyll, green leaf extract powder of bare barley, green juice powder of bare barley, green leaf extract of bare barley, titanium oxide, and talc.Examples of dyes include those used as a light-stabilizing substance. This preparation may contain other additives, if necessary, in addition to those described above, and any additive listed in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Code, the Japanese Pharmaceutical Excipients, and the Specifications and Standards for Use of Food Additives in Japan may be used. Furthermore, the proportion of such additives may be arbitrary. Specific examples of additives used in addition to those described above include a perfume and a sweetener. Specific examples of the perfume include an orange extract, orange oil, caramel, camphor, cinnamon oil, spearmint oil, a strawberry extract, a chocolate extract, a cherry flavoring, spruce oil, pine oil, peppermint oil, vanilla flavoring, strawberry flavoring, a bitter extract, a fruit flavoring, a mint extract, a blended flavoring, a mint flavoring, menthol, lemon powder, lemon oil, and rose oil, among which strawberry flavoring is preferred. Specific examples of the sweetener include aspartame, hydrogenated maltose starch syrup (maltitol), glycyrrhiza, xylitol, glycerin, saccharin, sucralose, D-sorbitol, acesulfame potassium, stevia, thaumatin, and advantame, among which sucralose is preferred. The present preparation may be in solid dosage form. Specifically, it may be a granule, a Page 20 of 50 fine granule, a tablet, a powder, a capsule, a pill or the like, and is preferably a granule, an oral suspension powder or a fine granule and, more preferably, a granule. A method for preparing a granule of the present preparation is not specifically limited, and is a method in which the active ingredients and additives, such as a binder and an excipient, are mixed to produce a mixed powder, and the mixed powder is granulated, and is preferably a wet granulation method in which granulation is carried out with water, water containing a binder, a solvent, or the like added, a dry granulation method in which compression molding is carried out without the use of water, or a melt granulation method. A Power Mill, a V-mixer, a mobile mixer, or similar equipment may be used as the machine to be used for mixing the active ingredients, additives, and the like.In addition, as a machine to be used for granulation, a wet pellet mill, a fluidized bed granulator, a mixing granulator, a dry crushing granulator, a melt extrusion granulator, or similar can be used. When the present preparation is a granule, the average particle size of the granule is in the range of 1 to 1000 pm. The preferred aspects will be described below. One aspect provides a solid dosage form containing (1) a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and (2) one or more selected from the group consisting of an alkali metal chloride, an organic acid, a polyhydric alcohol ester, and a fatty acid ester. Specific examples of the alkali metal chloride include sodium chloride and / or potassium chloride, and preferably sodium chloride. Specific examples of the organic acid include ascorbic acid and / or fumaric acid, and preferably fumaric acid. Specific examples of the polyhydric alcohol ester include Miglyol, triethyl citrate, and polyoxyethylene sorbitan monooleate. Specific examples of the fatty acid ester include triacetin. Another aspect provides a solid dosage form containing (1) a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, (2) one or more selected from the group consisting of an alkali metal chloride, an organic acid, an ester of IF-2019-6294743 5-APN-ANP#INPI 21 Page 21 of 50 hydrogenated maltose solid dose syrup mixture that (I) or a salt of this or more selected “ · · ··· - ““· ···. > l» .»a. - Yo". EiemninP°aS10y, preferably sodium chloride (malt,tol) and D-mannitol, hydrogenated maltose starch (maltitol) and D-mannitol Yet another aspect is provided, a form containing (1) a compound represented by the pharmaceutically acceptable formula, (2) one from the group consisting of an alkali metal chloride „„ · „ X :· “ ~·· ”-“· - -Χχχξ..: Furnáric EÍPmnin . . marico and, preferably, .-acid 2“' ““•“•““-“'XZ =“~“ΞΞηΓΠpurified anca and trehalose, preferably one or more selected from ΗίΧ'ΎΤΐθ6η 3ΖύΜΓ white PUri'iEach hydrogenated demaltose starch syrup (maltitol) and D-mannitol and. more preferably, hydrogenated maltose starch syrup (maltitol) and D-mannitol v ρπ η=Η· ι Page 22 of 50 A mixture of hydrogenated maltose starch syrup (maltitol) and D-mannitol. Specific examples of the water-soluble polymer include a cellulose-based polymer, an acrylic-based polymer, and a polyvinyl-based polymer, and preferably, a cellulose-based polymer. More specific examples of the cellulose-based polymer include carmellose, sodium carmellose, crystalline cellulose / sodium carmellose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose), methylcellulose, carboxymethyl ethylcellulose, hydroxyethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and a mixture of fumaric acid / stearic acid / polyvinyl acetal diethylamino acetate / hydroxypropyl methylcellulose, and preferably, hypromellose. In another aspect, a solid dosage form is provided containing (1) a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, (2) one or more selected from the group consisting of an alkali metal chloride, an organic acid, a polyhydric alcohol ester, and a fatty acid ester, (3) a sugar alcohol and / or a sugar, (4) a water-soluble polymer, and (5) an inorganic substance. Specific examples of the alkali metal chloride include sodium chloride and / or potassium chloride, and preferably sodium chloride. Specific examples of the organic acid include ascorbic acid and / or fumaric acid, and preferably fumaric acid. Preferred examples of the polyhydric alcohol ester include Miglyol, triethyl citrate, and polyoxyethylene sorbitan monooleate. Specific examples of the fatty acid ester include triacetin.Specific examples of sugar alcohol and / or sugar include one or more selected from the group consisting of isosomalt, hydrogenated maltose starch syrup (maltitol), mannitol, xylitol, erythritol, sorbitol, lactose, sucrose, fructose, maltose, purified white sugar, and trehalose; preferably, one or more selected from the group consisting of purified white sugar, hydrogenated maltose starch syrup (maltitol), and D-mannitol; and, more preferably, hydrogenated maltose starch syrup (maltitol) and D-mannitol; and, in particular, a mixture of hydrogenated maltose starch syrup (maltitol) and D-mannitol is preferred. Specific examples of water-soluble polymer include a cellulose-based polymer, an acrylic-based polymer, and a polyvinyl-based polymer; and preferably, a cellulose-based polymer. More specific examples of polymer a. IF-2019-6294743 5-APN-ANP#INPI23 Page 23 of 50 Cellulose base includes carmellose, sodium carmellose, crystalline cellulose / sodium carmellose, hydroxypropylcellulose, hypromellose (hydroxypropyl methylcellulose), methylcellulose, carboxymethyl ethylcellulose, hydroxyethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and a mixture of fumaric acid / stearic acid / polyphenyl acetal diethylamino acetate / hydroxypropyl methylcellulose, and preferably, hypromellose. Specific examples of the inorganic substance include light anhydrous silicic acid, nitrated silicon dioxide, sodium stearyl fumarate, and talc, and preferably, light anhydrous silicic acid and talc. In another respect, a solid dosage form is provided containing (1) a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and (2) a cellulose-based polymer. However, if a coating layer is formed on the solid dosage form, the coating layer does not contain a cellulose-based polymer. Specific examples of the cellulose-based polymer include carmellose, sodium carmellose, crystalline cellulose / sodium carmellose hydroxypropyl cellulose, hypromellose (hydroxypropyl methylcellulose), methylcellulose carboxymethyl cellulose, hydroxyethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose acetate succonate, hydroxypropyl methylcellulose phthalate, and a mixture of fumaric acid / stearic acid / polyvinyl acetal diethylamino acetate / hydroxypropyl methylcellulose, and preferably, hypromellose. In another aspect, a solid dosage form is provided containing (1) a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, (2) a cellulose-based polymer, and (3) an inorganic substance. However, if a coating layer is formed on the solid dosage form, the coating layer does not contain the cellulose-based polymer or the inorganic substance. Specific examples of the cellulose-based polymer include carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose / sodium carboxymethylcellulose, and hydroxypropyl methylcellulose. methylcellulose, carboxymethyl ethyl cellulose, hydroxyethylcellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, and a mixture of fumaric acid / stearic acid / polyvinyl acetal diethylamino acetate / hydroxypropyl cellulose, and preferably, hypromellose Page 24 of 50 Inorganic substances include light anhydrous silicic acid, hydrated silicon dioxide, sodium stearyl fumarate, and talc, and preferably light anhydrous silicic acid and talc. This preparation remains suspended in water even when supplemented with water before use and left for an extended period. For example, the suspension can be prepared by mixing the preparation with water. Alternatively, the suspension can be prepared by adding 20 ml of water to 2 g of the preparation and mixing. Furthermore, in another embodiment, the suspension can be prepared by measuring 20 ml of water and pouring it into the bottle containing the preparation. The contents are then gently shaken to avoid excessive foaming and ensure proper mixing of the preparation and water. Water suspensibility means that a visually uniform suspension forms when 9.5 ml of water are added to approximately 1 g of the preparation. These physical properties are sometimes collectively referred to as uniform dispersibility. The present preparation barely adheres to a surface of the container when added to the container. This preparation can prevent sticking between preparations after storage. As an indicator of the preparation's stickiness, the preparation is poured into a container, and its flow can be confirmed after inversion. This preparation can optimize production efficiency by improving flowability. The angle of repose can be used as an indicator of the preparation's flowability. The release rate of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof of the present preparation is 75% or more, preferably 80% or more and more preferably 85% or more, after 15 minutes from the start of the dissolution test in the dissolution test method (paddle method) stipulated in the 17th edition of the Japanese Pharmacopoeia. This preparation can be ingested directly by mouth, or it can be suspended in water or hot water, and then the suspension can be ingested. This preparation can be ingested by both Page 25 of 50 In particular, if it is for a child, the present preparation is suspended in water or hot water, and then the suspension of the present preparation can be ingested. EXAMPLES The present invention will now be described in detail with reference to the examples, comparative examples, and reference examples, and it should be noted that the present invention is not limited to these examples. A Compound II can be produced by a method disclosed in International Publication No. WO2016 / 175224. Example A Method of preparing Compound I [Formula 7] MeO O 0 O Á JL Potassium carbonate (1483.4 mg, 10.7 mmol), potassium iodide (549.5 mg, 3.3 mmol), tetrahydrofuran (33.1 g), N,N-dimethylacetamide (3.8 g), and water (80.3 mg) were added to Compound II (4.0 g, 8.3 mmol), and the mixture was stirred. The resulting mixture was heated to 60 °C, and chloromethylmethyl carbonate (1758.9 mg, 14.2 mmol) was added. The mixture was stirred at 60 °C for 9 hours and then cooled to 20 °C. Acetic acid (822.0 mg), 2-propanol (3.1 g), and water (20.0 g) were added, and the mixture was extracted twice with tetrahydrofuran (1.8 g, 8.9 g). The solvent was distilled through vacuum concentration to a liquid weight of about 32 g. The resulting liquid was heated to 45 °C, 2-propanol (1.6 g) was added, and the resulting liquid was cooled to 20 °C. An aqueous solution of sodium acetate prepared from sodium acetate (339.0 mg) and water (46.0 g) was added, and then it was cooled to 5 °C.After stirring the mixture at 5 °C for 3 hours, a pale yellow precipitate was filtered. The solid thus obtained was washed with a mixture of 2-propanol (4.7 g) and water (6.0 g), and the solid was washed again with 2-propanol (6.3 g). IF-2019-62947435 -ΑΡΝ-ΑΝΡ#ΙΝΡ^θ Page 26 of 50 To the pale yellow solid thus obtained, dimethyl sulfoxide (30.9 g) was added, and the mixture was stirred. The resulting solution was heated to 60°C, to which a mixture of dimethyl sulfoxide (2.2 g) and water (4.8 g) was added. Dimethyl sulfoxide (19.9 g) and water (28.4 g) were then added, and the mixture was cooled to 20°C. After stirring the solution at 20°C for 3 hours, a white precipitate was filtered off. The solid thus obtained was laundered with a mixture of dimethyl sulfoxide (8.0 g) and water (4.8 g), and then laundered again with water (12.0 g). The resulting solid was dried to obtain Compound I (4.21 g) as a white crystal. H-NMR (DMSO-D6) δ: 2.91-2.98 (1H, m), 3.24-3.31 (1H, m), 3.44 (1H, t, J = 10.4 Hz), 3.69 (1H, dd, J = 11.5, 2.8 Hz), 3.73 (3H, s), 4.00 (1H, dd, J = 10.8, 2.9 Hz), 4.06 (1H, d, J = 14.3 Hz), 4.40 (1H, d, J = 11.8 Hz), 4.45 (1H, dd, J - 9.9, 2.9 Hz), 5.42 (1H, dd, J = 14.4, 1.8 Hz), 5.67 (1H, d, J = 6 5 Hz)' 5.72-5.75 (3H, m), 6.83-6.87 (1H, m). 7.01 (1H, d, J = 6.9 Hz). 7.09 (1H, dd, J - 8.0, 1.1 Hz), 7.14-7.18 (1H, m), 7.23 (1H, d, J = 7.8 Hz), 7.37-7.44 (2H, m) X-ray diffraction of powder: 20 (·): The characteristic peaks are present at 8.6·±0.2·, 14.Γ10.2·. 17.4·±0.2·. 20.0'±0.2·. 24.0·±0 2' 26.3°±0.2°, 29.6°±0.2° and 35.4°±0.2°. The powder X-ray diffraction pattern of the Compound I crystal is shown in Figure 1. (1) Study in stabilizer In order to study a stabilizer, a stabilizer shown in each of Tables 2 to 4 and a compound represented by Formula (I) were subjected to wet granulation, and the amount of increase in the compound represented by Formula (II), which is a related substance, was evaluated after a temporary stability test of the produced granule. A preparation with a formulation shown in Table 1 was produced by the blending granulation method. [Table 1] Content (mg) Compound represented by Formula (1) 2.0 Purified white sugar 488.0 Hydrogenated maltose starch syrup (Maltitol) 500.0 IF-2019-62947435 -APN-ANP#INPI Page 27 of 50 Stabilizer 30.0 Hydroxypropylcellulose 10.0 Total 1030.0 (Method for preparing the preparation) A compound represented by Formula (I), purified white sugar, hydrogenated maltose starch syrup (maltitol) powder, a stabilizer, and hydroxypropylcellulose, as shown in Table 1, were mixed using a high-speed mixer (FS-GS SJT 10 high-speed mixer, Fukae Powtec Co., Ltd.), and water was added to the mixture, followed by granulation. The granulated product was then size-sorted in a Power Mill (model P3S, Showa Kagakukikai Co., Ltd.), and the resulting granules were dried at 65–70 °C in a fluidized bed granulator (WSG2&5 fluidized bed dryer granulator, Okawara Mfg. Co., Ltd.). After drying, a granule was obtained by size sorting in a Power Mill (model P-3S, Showa Kagakukikai Co., Ltd.). The granulation conditions in the high-speed mixer were as follows: (Granulation conditions) - Granulator: FS-GS SJT 10 High Speed ​​Mixer - Agitator rotation speed: 250 rpm - Blade rotation speed: 2500 rpm - Acceleration in solution injection: 21 ± 2 g / min - Moisture: 4 to 6.5% by weight - Grinding time: 1 min ± 5 sec (Temporal stability test of the preparation) ----The produced preparation was stored at 60 °C for 2 weeks, and the amount of increase in the compound represented by Formula (II), which is a related substance, was measured. (Stabilizer) As shown in Tables 2 to 4, the following stabilizers were used: sodium chloride (Kanto Chemical Co., Inc.), potassium chloride (Wako Pure Chemical Industries, Ltd.), ascorbic acid (Nacalai Tesque, Inc.), fumaric acid (Merck KGaA), Miglyol medium-chain fatty acid triglyceride (Mitsuba Trading Co., Ltd.), triethyl citrate (Merck KGaA), sodium nitrite IF-2019-62947435 -APN-ANP#INPI2g Page 28 of 50 (Nacalai Tasque. Inc.), glycerin (Kanto Chemical Co (Merck KGaA). Inc.), and vitamin E [Table 2] Example 1 Example 2 Example 3 Eigenln Δ Stabilizer Sodium chloride Potassium chloride Ascorbic acid Fumaric acid [Table 3] Stabilizer [Table 4] Stabilizer (Method p The quantity by means of chromated anditions: Example 5 Medium chain fatty acid triglyceride Miglyol Example compare Vitamin E to measure the compound ad of the liquid tography C tr íti ue r< id — E rr C( example 6 Ethyl nitrate vo 3 sto representadc os using Comparative Example 1 Sodium nitrite Comparative Example None measured by the Formula by the Formula the following Comparative Example 2 Glycerin Comparative 4 null (II)) (II) was measured methods and (measurement wavelength: - Detector: 260 nm ultraviolet absorbance meter - Column: XBridge C18, 3.5 pm, 3.0 x 150 mm - Column temperature: constant temperature of around 35 - Mobile phase A: 0.1% EDTA, mobile phase B: acetonitrile - Obtaining the trifluoroacetic acid / 0.2 mM phase of solution concentration in óonóe ta reladónTLZ'X · 7 to the mobile phase B was modified as shown in Table LT' [Table 5] IF-2019-62947435 -APN-ANP#INPI Page 29 of 50 Time after injection (min) O - 5 --------5 - 40 - 40.1 Mobile phase A (% by volume) --70 -> 20 —♦ 70 Mobile phase B (% by volume) ~30-30 -> 80 -> 30 - Flow rate: approximately 0.6 ml / min - Injection quantity: 5 μm - Sample cooler temperature: around 5 °C(1 ;3)'S°'UCÍÓn de laVad°Para au'd¡nyec <on mezcla de acetonitrilc / metanoí soluciír. oZaZsT;10'60de la - Equation to calculate the amount of Formula (II); Quantity of compound represented by the compound represented by the Formula (II) (%) =(AT|| / ..=== ·· —· - »“· » ·. .

[0073] (Results) Formula(l|)ae7d7'°<%' θ'C°mpPeS,° -Painted by ia Ejem os a ' OST 7eS'abi,'dad dapreparados deriosa 8 cL ,,emP'°S Comparatives 1 to 4 are shown in the Tables 6 or result, the amount of increase (%) in the compound <> - - —a da'03 Ejemp.csΪZ:: less than that in the granule that did not contain stabilizer dpi represented by Formula (II) snriin hOi E· -in the granules9U contained chloride of Example 1, ascorbic acid of Example 3, fumaric acid of E emo o05 í θ'trÍ9Cérid°de áC'd°9ras°de CadenaMiglyol of Example 5 was much smaller than that of the granule that did not contain stabilizer in Comparative Example 4. .IF.20l9.62947435-APN-ANP*INPI Page 30 of 50 [Table 6] Example 1 Example 2 Example 3 Example 4 Stabilizer Sodium chloride Potassium chloride Ascorbic acid Fumaric acid Amount of increase (%) in the compound represented by Formula (II) 0.70 1.31 0.28 0.30 [Table 7] Example 5 Example 6 Comparative Example 1 Comparative Example 2 Stabilizer Medium-chain fatty acid triglyceride Miglyol Triethyl citrate Sodium nitrite Glycerin Amount of increase (%) in the compound represented by Formula (II) 0.34 1.24 6.63 9.95 [Table 8] Comparative Example 3 Comparative Example 4 Stabilizer Vitamin E None Amount of increase (%) in the compound represented by Formula (II) 3.56 1.35 (2) Study in excipient In order to study an excipient, an excipient shown in each IF-20 !9-62947435-APN-ANP#INP¿1 Page 31 of 50 One of Tables 2 to 11 and a compound represented by Formula (I) were subjected to wet granulation, and the amount of increase in the compound represented by Formula (II), which is a related substance, was evaluated after a temporary stability test of the produced granule. (Method for producing the preparation) An excipient, shown in each of Tables 9 to 11, and a compound represented by Formula (I) were mixed in a bag in a 1:1 ratio. The mixture was then sieved through a 30-mesh sieve (0.22 mm mesh diameter). The sieved powder was mixed in a mortar, and purified water was gradually added to achieve a moisture content of approximately 5% by weight, based on the amount of materials used. The resulting mixture was then kneaded with a pestle. The kneaded product was size-sorted at moisture by hand-pressing it through a 16-mesh wire screen (0.55 mm mesh diameter). After size sorting, the granulated product was dried in a vented dryer, and a granule was prepared by hand-pressing it through a 20-mesh wire screen (0.40 mm mesh diameter). (Temporary stability test of the preparation) The resulting preparation was stored at 60 °C for 2 weeks, and the amount of increase in the compound represented by Formula (II), which is a related substance, was measured. (Excipient) As shown in Tables 9 to 11, the excipients used were purified white sugar (Merck KGaA), hydrogenated maltose starch syrup (maltitol. ROQUETTE), D-mannitol (ROQUETTE), lactose hydrate (DMV-Fonterra Excipients GmbH & Co. KG), sorbitol (Merck KGaA), erythritol (ROQUETTE), xyltol (ROQUETTE), and isomalt (Beneo-Palatinit GmbH).' [Table 9] Example 7 Example 8 Example 9 Excipient FTahla Purified white sugar i ni Hydrogenated maltose starch syrup (Maltitol) D-Mannitol | Example of | Example of । Page 32 of 50 Reference 1 2 Reference 3 Excipient Lactose hydrate Sorbitol Erythritol [Table 11] Reference example 4 Reference example 5 Excipient Xylitol Isomalt (Results) The percentage increase in the compound represented by Formula (II) in the temporary stability test of the preparations from Examples 7 to 9 and Reference Examples 1 to 5, and the melting point of each excipient, are shown in Tables 12 to 14. As a result, the percentage increase in the compound represented by Formula (II) in the granules of Examples 7 to 9 was slightly less than that of the granules of Reference Examples 1, 2, and 5. The percentage increase in the compound represented by Formula (II) in the granules of Reference Examples 3 and 4 was almost the same as that of the granules of Examples 7 to 9, while the melting point was lower compared to Examples 7 to 9; therefore, there was a possibility of stickiness. Consequently, purified white sugar, hydrogenated maltose starch syrup (maltitol) and D-mannitol were considered to be the preferred excipients. [Table 12] Example 7 Example 8 Example 9 Excipient Purified white sugar Hydrogenated maltose starch syrup (Maltitol) D-Mannitol Melting point (°C) 160 - 186 Ϊ45 166-168 Amount of increase (%) in the compound represented by Formula (II) 0.08 0.06 0.11' IF-2019-6294743 5-APN-ANP#INPI33 Page 33 of 50 f I I i li [Table 13] Reference Example 1 Reference Example 2 Reference Example 3 Melting Point (°C) Lactose Hydrate 20°C - 20°C ........ Sorbitol fl oz............... Erythritol Amount of 121 increase (%) in the compound represented by Formula (II) 0.17 0.15 0.08 [Table 14] Excipient Reference Example 4 Xylitol Reference Example 5 Isomalt Amount of increase (%) in the compound represented by Formula (II) U2 - yg· 0.04 0.38 161......—' (3) Study in combination of excipients although purified white sugar, hydrogenated syrup (maltitol) and D-mannitol were selected; —. ,=«=·.=:=; t· which is a substance related^^by the^formula (II), adherence to the container,(d) the yield of Zgranute fineZ 7 apparent density A nr^nor fine granule, and (e) each of the Tabias5 yeTf™,aCÍÓn« — in per mixture,?θ 'θ0™'6θ'mét°d° «° annulment maltose starch [Table 151 IF-2019-62947435 -APN-ANP#INPI Page 34 of 50 Example 10 (weight in mg) Example 11 (weight in mg) Example 12 (weight in mg) Compound represented by Formula (1) 10.0 20.0 10.0 Maltitol 300.0 350.0 490.0 D-Mannitol 614.0 554.0 490.0 Purified white sugar - - - Sodium chloride 30.0 30.0 - Polyvinylpyrrolidone k25 10.0 10.0 10.0 Total Weight ratio of sugar or sugar alcohol Table 1R1 964.0 Maltitol: D-Mannitol = 32.8:67.2 964.0 Maltitol: D-Mannitol = 38.7:61.3 1000.0 Maltitol: D-Mannitol = 50.0:50.0 Comparative Example 5 (weight in mg) Comparative Example 6 (weight in mg) Compound represented by Formula (I) 10.0 10.0 Maltitol 500.0 - D-Mannitol - 500.0 Purified white sugar 480.0 480.0 Sodium chloride - - Polyvinylpyrrolidone k25 io.o 10.0 Total 1000.0 1000.0 Weight ratio of sugar or sugar alcohol Maltitol: Purified white sugar = 51.0:49.0 D-Mannitol: Purified white sugar = 51.0:49.0 (Method for producing the preparation) IF-2019-62947435 -APN-ANP#INPI Page 35 of 50 A compound represented by Formula (I), an excipient, and polyvinylpyrrolidone, shown in Tables 15 and 16, were mixed using a high-speed mixer (LFS-GS-2J high-speed mixer, Fukae Powtec Co., Ltd.), and water was added to the mixture, followed by granulation. The granulated product was then size-sorted in a Power Mill (model P-3S, Showa Kagakukikai Co., Ltd.), and the resulting granules were dried at 65–70°C in a fluidized bed granulator (MP-01 fluidized bed dryer granulator, Powrex Corp.). After drying, a granule was obtained by size sorting in a Power Mill (model P-3S, Showa Kagakukikai Co., Ltd.). The granulation conditions in the high-speed mixer were as follows: (Granulation conditions) - Granulator: LFS-GS-2J high-speed mixer - Agitator rotation speed: 333 rpm - Blade rotation speed: 2500 rpm - Acceleration in solution injection: 20 ± 3.5 g / min - Moisture: 3 to 7.5% by weight - Crushing time: 1 to 2 min ± 5 sec (Suspensibility test of the preparation in water) The number of times inversion mixing was required to prepare a visually uniform suspension when 9.5 ml of water was added to approximately 1 g of the present preparation was recorded. (Adherence to the container of the preparation) In the production of this preparation, the amount of granulation product adhering to the inner wall of a granulator mixer after granulation was visually confirmed. The presence or absence of adhesion after scraping was evaluated as an index of adherence to the container. (Measurement of the yield of the fine granule of the preparation) 100 g of the present preparation were sieved through sieves No. 30 and 140, and the ratio of the amount of a granule that passes through sieve No. 30 and one remaining in sieve No. 40 was calculated with respect to the total amount of sieved granule. (Measurement of the apparent density of the preparation) IF-2019-62947435 -APN-ANP#INPI Page 36 of 50 The mixture was injected into a container (capacity: 100 ml) until it overflowed, and the mixture was carefully leveled to remove any excess from the top surface of the container. The weight of the mixture in the container was obtained from a previously tared container, and the apparent density was determined according to the following equation: Apparent density = Weight of the preparation in the container / 100 (Excipient) As shown in Tables 15 and purified (Merck KGaA), starch syrup of ROQUETTE), and D-mannitol (ROQUETTE) (Results) 16, hydrogenated maltose white sugar (maltitol, in combination as the excipient) was used. The water suspensibility, container adherence, fine granule yield, and bulk density of the preparations in Examples 10 and Comparative Examples 5 and 6 are shown in Tables 17 and 18. As a result, the preparations in Examples 10 to 12, which contained a mixture of hydrogenated maltose starch syrup (maltitol) and D-mannitol as an excipient, had excellent water suspensibility, poor container adherence, and a bulk density of 0.5 g / ml or more. Particularly in Examples 10 and 11, the fine granule yield was also as high as 90% or more. On the other hand, the preparations in Comparative Examples 5 and 6, which contained a mixture of purified white sugar and hydrogenated maltose starch syrup (maltitol) or purified white sugar and D-mannitol as an excipient, were inferior in terms of water suspensibility compared to the Examples and also had greater adherence to the container.In particular, in Comparative Example 6, the performance of the fine granules was also low. [Table 17] Suspensibility in water Example 10 Suspended uniformly 15 times Example 11 Suspended uniformly 10 times Example 12 Suspended uniformly 10 times Low Adhesion to container Low Low Fine granule yield (%) 92 90 IF-2019-62947435- 72 APN-ANP#INPI 37 Page 37 of 50 I Apparent density (g / ml) | 0.67 ' Γ o.67 [Table 18] Comparative Example 5 Comparative Example 6 Suspensibility in water Suspended uniformly 25 times Suspended uniformly 30 times Adhesion to container Greater Greater Fine granule yield (%) 89 66 Apparent density (g / ml) 0.76 0.65 (4) Binder study In order to study a binder, a binder shown in Table 19 and a compound represented by Formula (I) were subjected to wet granulation, and the resulting preparation was evaluated to determine (a) the amount of increase in the compound represented by Formula (II), which is a related substance, after a temporary stability test and (b) its bulk density. A preparation with a formulation shown in Table 19 was produced by the agitation granulation method. Polyvinylpyrrolidone K25 (BASF) and hydroxypropylcellulose SL (Shin-Etsu Chemical Co., Ltd.) were used as binders. [Table 19] Example 13 (weight in mg) Example 14 (weight in mg) Reference Example 6 (weight in mg) Compound represented by Formula (1) 10.0 10.0 10.0 Purified white sugar 480.0 460.0 480.0 Hydrogenated maltose starch syrup (Maltitol) 500.0 500.0 500.0 Polyvinylpyrrolidone K25 10.0 30.0 - IF-2019-62947435 - A PN-AN P# IN P^8 Page 38 of 50 Hydroxypropylcellulose SL Total --------- H000.0 1000.0 10.0 1000.0 using a (Method for producing the preparation) A compound represented by the formula fn · Purified, maltose starch syrup 7 hydroxypropylcellulose SL <Nippon Soda Co Ltd) r θ como aglutinante que se muestran en la Tabía19’PO'nilpirrolidopa«25 mezclador de alta vninnw °a 19 semezclaron Powtee Co., Ltd ) X* »d--GS.2J,Fukaeagitation. Then, the product of 3 me“,a'se3u,da degranulation by size in a Power Mill (model PS^Sho 7porresultante was dried from 65 to 70 -Ce 'Ka3akukil <m Co., Ltd.), ye| (granulador de secador de lecho McUzLoMPo^de SeCarse·se obl™ un gránulo por selección por t “θ^8(modelo P-3S, Showa Kagakukikai Co Ltd) Laa™n°en una p°«mr Mili en a) mezo.ador de afia ve.ocidad fueron tas siguió (Condiciones de granulación) - Granulator: LFS-GS-2J high-speed mixer - Agitator rotation speed: 333 rpm - Blade rotation speed: 2500 rpm - Acceleration in solution injection: 20 ± 35 a / min - Moisture: 3 to 7.5% by weight ® - Grinding time: 1 to 2 min ± 5 sec (Temporary stability test of the preparation) The produced preparation was stored for 2 weeks, and the amount of increase in the mass was measured, which is a substance related by the formula (Measurement of the apparent density of the preparation) until overflowing. The preparation was then filled (capacity: 100 ml) to remove an excess of the material from the container. The weight of the preparation was obtained from the preparation. Page 39 of 50 (Results) The amount of stability in the compound - represented by formula (II) in the temporal stability test of the preparations of Examples 13 and 14 and Reference Example 6, and the apparent density is shown in Table 20. The amount of stability represented by formula (II) in the temporal stability test of the preparations of Examples 13 and 14 and Reference Example 6 was less than that of the preparation of Example 7 (Reference Example 6). The amount of stability represented by formula (II) in the temporal stability test and the apparent density in the preparation of Example 12 are less than that of Example 7. % Weight were lower than those of the preparation in Example 13 in which the amount of polyvinylpyrrolidone was 3% by weight. [Table 20] Amount of increase (%) in the compound represented by Formula (II) Example 13 0.12 Example 14 0.15 Reference example 6 0.20 Apparent concentration (g / ml) 0.72 0.77 — - (5) Study on fluidizing agent In order to study a fluidizing agent, (a) the amount of related substances after temporary separation of the prepared mixture and (b) the stickiness between mixtures were evaluated. A mixture with a formulation shown in Tables 21 and 22 was produced using the blending granulation method. 1% and 3% of light anhydrous silicon dioxide (Cabot Corp.), 1% and 3% of hydrated silicon dioxide (PRUV, JRS Pharma), and 1% of hydrated silicon dioxide (PRUV, JRS Pharma) were used as the fluidizing agent. [Table 21] IF-2019-62947435 -APN-ANP#INPI Example 15 Example 16 | Example 17 Page 40 of 50 (weight in mg) (weight in mg) (weight in mg) mg) Compound represented by Formula (1) 10.0 10.0 10.0 Hydrogenated maltose starch syrup (Maltitol) 490.0 490.0 490.0 D-Mannitol 490.0 490.0 490.0 Polyvinylpyrrolidone k25 10.0 10.0 10.0 Its era the a ” Tó Tó~ Tó Light anhydrous silicic acid 30.0 Hydrated silicon dioxide 10.0 Sodium stearyl fumarate - Strawberry flavoring Tó Tó Tó 1 total 1016.0 1036.0 1016.0 [Table 22] Example 18 Example Example (weight in mg) 7 8 (weight in mg) Compound represented by Formula (I) 10.0 10.0 10.0 Hydrogenated maltose starch syrup (Maltitol) 490.0 490.0 490.0 D-Mannitol 490.0 490.0 490.0 Polyvinylpyrrolidone k25 10.0 10.0 Sucralose - Light anhydrous silicic acid - Hydrated silicon dioxide 30.0 Sodium stearyl fumarate - 10.0 30.0 Strawberry flavoring - 3.0 Total 1036.0 1016.0 1036.0 IF-2019-6294743 5-ΑΡΝ-ΑΝΡ#ΙΝΡ^ Page 41 of 50 (Method for producing the preparation) A compound represented by hydrogenated maltose (maltitoh nm·, ,(l)' “θstarch of_________.. . <ma'tltOl)·D-manlto1· PoIMnllpIrrolldona K25, sucralosa, un agente fluidizante (cualquiera de ácido silícico anhidro liviano, dióxido de rr-z--·:-·» -........ mezcla, liado el 1“ θSegUida de granulac™ Por (Condiciones de granulación) - Granulator: LFS-GS-2J high-speed mixer - Agitator rotation speed: 333 rpm - Blade rotation speed: 2500 rpm - Acceleration in solution injection: 20 ± 3.5 g / min - Moisture: 3 to 7.5% by weight - Grinding time: 1 to 2 min ± 5 sec (Temporary stability test of the preparation) The resulting preparation was stored at 60°C for 2 weeks, and the amount of increase was measured using the formula ΠΒ nno θcomPuestorepresentado P formula (II), which is a related substance. -------(Test of stickiness of the preparation) 9 of the preparation was loaded into a brown 4 ml bottle. (Results) IF-2019-62947435 -APN-ANP#INPI Page 42 of 50 The amount of increase or> -i r-. , increase ( / 0) in the compound represented by the Examples 15'iA “θ '°S prepared '·» examples 15 to 18 and comparative examples 7 and 8. and the adhesion between: “eSreS,ran βΠ bS Tab'aS 23 V 24'C°-° -itado, i eanhdad de Aumenta (· / .) en el compuesto represented by Formula (II) en os preparas de tos Ejemp.es 15 a 18 fue casi ,a misma que ei eZ sL : fE,eniP'0S C°mPara,iV0S 7 Zθ -6de Meanwhile, as a result of analyzing the stickiness of the preparations from Examples 15 to 18 and Comparative Examples 7 and 8, the preparations from Examples 15 to 18 showed less stickiness than the preparations from Comparative Examples 7 and 8. [Table 23] Example 15 Example 16 Example 17 Amount of increase (%) in the compound represented by Formula (II) 0.64 0.51 0.34 Stickiness ~Δ ' O “o [Table 24] increase (%) in the Example 18 Comparative Example 7 Comparative example 8, composed of 0.58

[0082] (6) Study on suspension agent In order to study a suspension agent of a preparation in water, formulation shown in Table 25, the granulation by mixing was evaluated. The present preparation was produced using the method of Hypromellose (TC-5, Shin-Etsu Chemical Co. ItriJl· IF-2019-6294743 5-APN-ÁNPfflNPT Page 43 of 50 hydroxypropyl cellulose (HPC-L. Nippon Soda Shin-Etsu Chemical Co., Ltd.) Co., Ltd.), and methyl cellulose (SM-4, [Table 25] were used as the agent of Example (weight mg) | Compound represented by Formula (I) D-Mannitol Starch syrup 20.0 564.0 suspension. in Example of Example Example reference 7 1 of 1 / -- í MC comparative (reference weight θπ or 9 mg) 8 1(weight in (weight in mg) 1 mg) 20.0 20.0 । | 20.0 5647o- Γ 564.0 7 364.0 ¡ 350.0 hydrogenated maltose (Maltitol) Sodium chloride |Polyvinylpyrrolidone Hypromellose '^droxy^piiHelüfosa MethiTcellulose Sucralose r 350.0 30.0 10.0' 3¡0~ 30.0 W 3.0 Light anhydrous silicic acid Strawberry flavoring Total -----5.0 5.0 20.0 20.0 1.0 1003.0 1.0 T003.0 350.0 353.0 1 30,Ó |3o7b 10.0 I io,ó ”3^ I - l^o- 20.0 20.0 ϊ,ο |To -------- - 1003.0 1003.0 (Method for producing the preparation) starch^ '°'D'mani'o1· 'arabe demaltose hydrogenated (maltitnh polyvinylpyrrolidone K25 shown in Table 25 ' a vertios granulator, (model VG-50, Powrex Coro t “meZC'ar°nmezcla, followed by granulation by agitation^θ90 agUa a lagranulación was subjected to selection by t»m- '9°'product°de 3S, Showa Kagakukikai Co Ltd > , θΡ°βΓ Μ'(model°ρ' IGo·'Ltd·)- and the resulting Page 44 of 50 fluidized bed granulator (GPGC-15&30 granulator, Powrex Onm \ was carried out in u„ p ' θ' 'a Sa,eccióp°r Lid ) The product d ' '““θ'0 P'3S'Sh°Wa Ka9«kukfkaí Co„ mixed with sucrai 'θP°r ,a™fl° “ hydroxypropylcelluloseάθhypromellose· xrr--·—30fabnCad°Por Toku(uθθΦ.) to obtain a granule. (Granulation conditions) - Granulator: VG-50 vertical granulator - Agitator rotation speed: 200 rpm - Blade rotation speed: 2500 rpm fluidized bed dryer - Acceleration in solution injection: - Moisture: 4.5 to 7.5% by weight - Crushing time: 1 to 3 min ± 5 sec (Suspension test of the preparation) 105 ± 3 g / min in water) of the present preparation was added to a stoppered container that was heated 40 times and immediately afterwards, a liquid was collected from the collected portions. The concentration of the compound represents the formula (I) in the liquids contained 9.5 g / min. (Method for measuring the compound The amount of the compound represented by Formula (I)) by liquid chromatography conditions: by the Formula using the following (Or measured methods and 260 nm)De,eC,Or: absORCIOME,r°ultra™leta (wavelength of Corp)'C°IUmna: ACQUITY UPL0 BEH C18 V Pm·2·' '50la medir: mm (Watersc- Column temperature: constant temperature of around 35 Mobile phase A. 0.1% trifluoroacetic acid / 0.2 ml of solution of IF-2019-6294743 5-APN-ANP#INPI Page 45 of 50 EDTA, mobile phase B: acetonitrile - Obtaining the mobile phase: controlled for a concentration gradient where the mixing ratio of mobile phase A with respect to mobile phase B was modified as shown in Table 26 [Table 26] Time after injection (min) n _ o Mobile phase A (% by volume) Mobile phase B (% by volume) 2.3 - 3 -------- 3-4 —'-------- 62 62 —> 20 36 38 -> 80 O - zu 6U - Flow rate: approximately 0.6 ml / min - Injection quantity: 4 μm - Sample cooler temperature: around 5 °C - Autoinjector flushing solution: acetonitrile '· “·· ··— · ' « - Equation to calculate the amount of Formula (I); Quantity of the represented compound χΑτ / Asx 100 MS: amount weighed (mg) compound represented by the Formula (I) (%) = MS / C C: quantity labeled on the preparation (mg / ml) As: peak area obtained from standard solution AT: peak area obtained from sample solution (Suspensibility evaluation in water) The suspensibility of the preparation was evaluated as follows: according to the following equation: Ratio (%) of the amount of compound represented by Formula () in suspension in the central position of the container after 0 minutes the F rrnZm en6'=«θ' represented by m n. heSUSPenS'°n elaΡ°θ'θ'° central position of the container after recr .“h “θ' 'c0cet™i°n of the compound represented by Formula (I) in suspension in the central position of the container immediately after the invAr.inn h > · pe the inversion of the container) χ inn í%i IF-2019-6294743 5 -ΆΡΝ-ΆΝΗπΝΡΙ Page 46 of 50 (Results) The water suspensibility of the preparations from Example 19, Reference Examples 7 and 8, and Comparative Example 9 is shown in Table 27. As a result, the ratio of the amount of compound represented by Formula (I) in the suspensions from Example 19 and Reference Examples 7 and 8 was higher than that of the suspension from Comparative Example 9, which did not contain a suspending agent. In particular, the preparation from Example 19 containing hypromellose had a higher ratio of the amount of compound represented by Formula (I) in the suspension and exhibited good water suspensibility. [Table 27] Ratio (%j of ía~ amount of compound represented by Formula (|) in suspension in the central position of the container after 10 minutes of inversion of the container Example 19 95.1 Reference example 7 93.0 Reference example 8 92.9 Comparative example 9 65.8 (7) Lubricant study ----=------- In order to study a lubricant, the angle of repose was evaluated as a melt flow index of a preparation. A preparation with a formulation shown in Table 28 was produced by the agitation granulation method. Talc (Merck KGaA, LUB) was used as the lubricant [Table 28]. Example 20 (weight in mg) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Comparative Example 10 (weight in mg) IF-2019-62947435 -APN-ANP#INPI Page 47 of 50 Compound represented by Formula (1) 20.0 20.0 D-Mannitol 560.0 561.0 Hydrogenated maltose starch syrup powder (Maltitol) 350.0 350.0 Sodium chloride 30.0 30.0 Polyvinylpyrrolidone 10.0 10.0 Hypromellose 3.0 3.0 Sucralose 5.0 5.0 Light anhydrous silicic acid 20.0 20.0 Talc 1.0 Strawberry flavoring 1.0 1.0 Total 1000.0 1000.0 (Method for producing the preparation) A compound represented by Formula (I), D-mannitol, hydrogenated maltose starch syrup (maltitol), sodium chloride, polyvinylpyrrolidone K25, and hypromellose, as shown in Table 28, were mixed using a vertical granulator (model FM-VG50, Powrex Corp.), and water was added to the mixture, followed by agitated granulation. The granulated product was then size-sorted in a Power Mill (model P3S, Showa Kagakukikai Co., Ltd.), and the resulting product was dried at 65–70 °C in a fluidized bed granulator (GPGC-15&30 fluidized bed dryer granulator, Powrex Corp.). After drying, size sorting was performed in a Power Mill (model P-3S, Showa Kagakukikai Co., Ltd.). The granulation product after size selection was mixed with talc, sucralose, light anhydrous silicic acid and strawberry flavoring using a V-shaped mixer (130 I V-type mixer, Tokuju Corp.) to obtain a granule. (Granulation conditions) - Granulator: VG-50 vertical granulator - Agitator rotation speed: 200 rpm - Blade rotation speed: 2500 rpm - Acceleration in solution injection: 105 ± 3 g / min - Moisture: 4.5 to 7.5% by weight IF-2019-62947435-APN-ANP#INPI Page 48 of 50 - Grinding time: 1 to 3 min ± 5 sec (Measurement of the angle of rest of the preparation) ~ «·»>« X: “ “1“ prepared from the Example as a formative fluidity of the prepared may Example 20 Angle of repose (°) 33.7 Comparative example 10 36.2' (8) Measurement of release speed The preparation of Example 20 shown in Table 28 -r with SP (aluminum) was stored at 25 C v 60 »7 of h lí 19 moe. of relative humidity for months, and the release rate was measured by Formula (I). compound represented (Test of dissolution property of the preparation) The prepared product was packaged rnn qd ii · · i C and 60% relative humidity during 38B “2 m * cetyltrimethylammonium), and the rotation speed of ρ^Γ' rpm. (Results) As shown in Figure 2, the rate of release of the preparation from Example 20 after storage at relative humidity for 3 6 qv 19 m rate Hp γη7θ5 CaS'n°SeVenció of the preparation's release was established at 50% of the 'C and 60% of Page 49 of 50 preparation.

[0088] (9) Prepared with different content of the compound Example 21 shown in Table 29 was prepared in the same way as Example 20 using the agitation granulation method [Table 29] Compound represented by Formula (1) D-Mannitol -------------— “Hydrogenated maltose starch syrup powder (Maltitol) Sodium chloride 7 Tolyvinylpyrrolidone ' Hypromellose ' ---:-- Example 21 (weight in mg) “40.0 ~ *540.0 350.0 *30.0 ' Ίο, o το OubidlOSS -- 5.0 Light anhydrous silicic acid Talc ' ---------- 20.0 To ' Strawberry flavoring --- Total : --- 1.0 ”1000.0 INDUSTRIAL APPLICABILITY The present preparation containing the compound represented by Formula (I) has been improved in stability, water suspensibility, flowability, etc. through various studies. This allows the present preparation to be suspended in water, and the present preparation can be easily ingested, even by children. IF-2019-62947435 -APN-ANP#INPI Page 50 of 50 Argentine Republic - National Executive Branch 2019 - Year of Exports Additional Signature Sheet Graphic Report Number: IF-2019-62947435 -APN-ANP#INPI CITY OF BUENOS AIRES Friday, July 12, 2019 Reference: 20190101070 The document was imported by the GEDO system with a total of 50 page(s). Digitally signed by GESTION DOCUMENTAL ELECTRONICA - GDE DN: cn=ELECTRONIC DOCUMENTARY MANAGEMENT - GDE, c=AR, o=GOVERNMENT SECRETARY OF MODERNIZATION, ou=ADMINISTRATIVE MODERNIZATION SECRETARY, serialNumber=CUIT 30715117564 Date: 2019.07.12 16:19:08 -03'00' Jimena Bengolea Technical Analyst National Patent Administration National Institute of Industrial Property Digitally signed by GESTION DOCUMENTAL ELECTRONICA GDE DN: cn=GEST10N ELECTRONIC DOCUMENTARY - GDE, c=AR, o=SECRETARY OF GOVERNMENT OF MODERNIZATION, ou=SECRETARY OF ADMINISTRATIVE MODERNIZATION, serialNumber=CUIT 30715117564 Date: 2019.07.12 16:19:09 -03'00'

Claims

1. A solid pharmaceutical composition characterized in that it comprises a compound represented by the following formula (I): [Formula 1] or a pharmaceutically acceptable salt thereof, and one or more stabilizers selected from the group consisting of sodium chloride, ascorbic acid, fumaric acid, and medium-chain fatty acid triglycerides, wherein the content of the compound represented by formula (I) or the pharmaceutically acceptable salt thereof is from 1 to 4% by weight, with respect to the total amount of the solid pharmaceutical composition, and wherein the content of the stabilizer is from 0.1 to 5% by weight, with respect to the total amount of the solid pharmaceutical composition. Seven claims follow.