Coating formulation

Abstract

To provide a coated preparation obtained by coating a thermally expandable core with two or more coating layers.SOLUTION: A coated preparation comprising a core coated with two or more coating layers, wherein the two or more coating layers comprise (1) a coating layer A comprising a coating base comprising a high molecular weight polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and a polyvinyl alcohol, wherein the ratio of the high molecular weight polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol is 0.1:1 to 3:1, and (2) a coating layer B comprising a coating base comprising methylcellulose.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a coated preparation in which a core that expands in thickness due to heat is coated with two or more coating layers, and to an improvement in the poor appearance of a preparation that expands in thickness due to heat. [Background technology]

[0002] Among the active ingredients and excipients contained in solid dosage forms, some interact with each other due to heat during storage, causing the thickness of the solid dosage form to expand. Such expansion can cause significant changes in the dosage form, such as cracking, and impair the appearance quality of the dosage form.

[0003] Patent Document 1 describes a preparation having a coating layer that may contain hypromellose, methylcellulose, and polyvinyl alcohol, and that is further coated with a polymer that dissolves at a pH of 5 or higher. However, there is no description that the coating layer of a polymer that dissolves at a pH of 5 or higher contains hypromellose, methylcellulose, or polyvinyl alcohol. Furthermore, Patent Document 2 describes that for coating oral tablets, two or more coating layers are preferably used, with a primary coating using hypromellose and a secondary coating using polyvinyl alcohol, and describes in Example 1 that double coating is performed with two types of coating agents, with Opadry® containing hypromellose as the main component being used for the primary coating and Opadry® containing polyvinyl alcohol as the main component being used for the secondary coating. However, there is no description of coating with a coating layer containing polyvinyl alcohol together with methylcellulose or hypromellose.

[0004] Furthermore, none of the above documents mentions the problem of thickness expansion caused by heat during storage, resulting in defects in appearance such as cracks in the preparation. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 7-112932 [Patent Document 2] Special Table 2019-534887 Summary of the Invention [Problem to be solved by the invention]

[0006] Some ingredients cause thickness expansion due to heat during storage, and this expansion can cause significant changes such as cracking in the formulation, impairing the appearance quality of the formulation. For example, in a solid formulation containing vitamin B1 and nicotinic acid in a given ratio in physical contact with each other, the thickness of the formulation can expand due to heat during storage, causing significant changes such as cracking in the formulation.

[0007] Therefore, an object of the present invention is to provide a coated preparation in which poor appearance such as cracking of the preparation due to expansion is improved, particularly in solid preparations that expand due to heat, in which poor appearance such as cracking of the preparation due to expansion is improved. [Means for solving the problem]

[0008] As a result of intensive research into solving the above-mentioned problems, the present inventors have found that poor appearance such as cracks in the formulation due to expansion can be improved by coating the core with two or more coating layers, including: (1) a coating layer comprising a coating base containing a polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton to the polyvinyl alcohol is 0.1:1 to 3:1, and (2) a coating layer comprising a coating base containing methylcellulose, and have thus completed the invention. That is, the present invention includes the following aspects. [1] A coated formulation in which a core is coated with two or more coating layers, wherein the two or more coating layers are: (1) A coating layer A including a coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol is 0.1:1 to 3:1; and (2) Coating layer B containing a coating base containing methylcellulose A coating formulation comprising: [2] The coated formulation according to [1], wherein the amount of methylcellulose contained in coating layer B is 0.8% or more based on the mass of the core. [3] The coated formulation according to [1] or [2], wherein the total amount of the coating base contained in coating layer A and coating layer B is 4% or more of the mass of the core. [4] The coating formulation according to any one of [1] to [3], wherein the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton is methylcellulose or hypromellose. [5] The coated preparation according to any one of [1] to [4], wherein the core contains vitamin B1 and nicotinic acids. [6] The coated formulation according to [5], wherein the vitamin B1 group is selected from fursultiamine or a salt thereof and thiamine nitrate. [7] The coated formulation according to [5] or [6], wherein the nicotinic acid is nicotinamide. [8] The coated formulation according to any one of [5] to [7], wherein the core further contains a herbal medicine or an extract thereof. [9] The coated formulation according to [8], wherein the herbal medicine or extract thereof comprises at least one selected from Astragalus Root, Shigoka, Ginseng, Eucommia Root, Peony Root, Poria Cocos, Dioscorea Root, Cinnamon Bark, Lycium Bark, Scutellaria Root, Fennel, Astragalus Root, Lithospermum Parkii, Lithospermum Root, Tangerine Peel, Cistanche Salicylate, and Longan Fruit, and extracts thereof.

[10] The coated formulation according to [8], wherein the herbal medicine or extract thereof comprises at least one selected from Astragalus Root, Shigoka, Ginseng, Eucommia Root, Peony Root, Poria Coccus, Dioscorea Root, Cinnamon Bark, Lycium Bark, and Atractylodes Rhizome, and extracts thereof.

[11] A method for producing a coated formulation in which a core is coated with two or more coating layers, a step of coating the core with a coating layer A containing a coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol in the coating layer A is 0.1:1 to 3:1; and a step of coating the core with a coating layer B containing a coating base containing methylcellulose; A manufacturing method comprising: [Effects of the Invention]

[0009] According to the present invention, it is possible to improve appearance defects such as cracks in a coated preparation due to expansion. Therefore, according to the present invention, it is possible to provide a coated preparation in which appearance defects such as cracks in a preparation due to expansion are improved. Furthermore, according to the present invention, it is possible to provide a coated preparation in which appearance defects such as cracks in a preparation due to thickness expansion are improved in a solid preparation that undergoes thickness expansion due to heat. Furthermore, according to the present invention, it is possible to provide a coated preparation in which appearance defects such as cracks in a preparation due to thickness expansion are improved in a solid preparation, such as a tablet, containing a vitamin B1 class and a nicotinic acid class, which leads to a reduction in tablet size and is easy to take, and which has excellent takeability. DETAILED DESCRIPTION OF THE INVENTION

[0010] As used herein, the term "core" refers to a formulation before it is coated with a coating layer. The "core" as used herein is not particularly limited in shape, size, form, etc., as long as it can be coated with a coating layer, and is, for example, a solid formulation, preferably a tablet, granules, granules, or powder, more preferably a tablet. As used herein, when the "core" is a tablet, the "core" may also be referred to as a "plain tablet."

[0011] As used herein, the term "coated preparation" refers to a preparation in which a core is coated with a coating layer. The "coated preparation" as used herein is not particularly limited in shape, size, form, etc., and is, for example, a solid preparation, preferably a tablet, capsule, granule, or powder, more preferably a tablet. As used herein, when the "coated preparation" is a tablet, the coated preparation may be referred to as a coated tablet, and the core may be referred to as a plain tablet.

[0012] In one embodiment, the "core" herein, for example, a plain tablet, is a preparation that undergoes swelling, preferably a preparation that undergoes thickness swelling, more preferably a solid preparation that undergoes thickness swelling due to heat.The "core" herein preferably contains vitamin B1 and nicotinic acids, more preferably vitamin B1, nicotinic acids, and herbal medicines or extracts thereof.The "core" herein may contain active ingredients and additives other than vitamin B1, nicotinic acids, and herbal medicines or extracts thereof, as long as they do not inhibit the effects of the present invention.

[0013] In this specification, the expansion can be evaluated using evaluation methods and standards commonly used in the formulation technical field, and can be expressed, for example, as the increase in the volume or thickness of the formulation. When the formulation is in the form of a tablet, it can be expressed, for example, as the increase in the thickness or diameter of the tablet, preferably the increase in the thickness of the tablet. In one embodiment, the term "swelling" as used herein refers to the expansion of a formulation due to heat, preferably to an increase in the thickness or diameter of a formulation due to heat during storage. For example, a formulation can be said to have expanded if the increase in thickness or diameter of the formulation after a certain period of storage is 1% or more, preferably 5% or more, compared to the thickness or diameter of the formulation at the start of storage. The term "swelling" as used herein can refer not only to an increase in the thickness or diameter of the formulation, but also to the occurrence of cracks or the like due to the expansion of the formulation after a certain period of storage. "Heat during storage" herein can be, for example, 1, 2, 3, 6, 9, 12, 18, 24, 30, or 36 months at 25°C, 1, 2, 3, 4, 5, or 6 months at 40°C, 1, 2, 4, 6, 8, or 12 weeks at 50°C, 7, 14, or 21 days at 60°C, or an amount of heat equivalent thereto.

[0014] In this specification, the appearance defect of a formulation and its improvement can be evaluated using evaluation methods and standards commonly used in the formulation technical field. For example, the appearance defect of a formulation can be evaluated according to the method described in the examples below, and the incidence of appearance defect can be determined by determining the appearance defect and its improvement. In one embodiment, "poor appearance" means that significant defects, such as swelling in thickness or cracks, are observed in the appearance of a formulation after storage for a certain period of time. In one embodiment, "improvement of poor appearance" means that the appearance of a formulation after storage for a certain period of time is within the acceptable range of quality from the viewpoint of product supply. For example, when the incidence of poor appearance, as evaluated according to the method described in the Examples below, is less than 20%, preferably less than 10%, it can be said that poor appearance has been improved.

[0015] The storage method, period, temperature, humidity, etc. of the solid preparation herein are not particularly limited as long as they are commonly used in the pharmaceutical technical field, and may be, for example, 1, 2, 3, 6, 9, 12, 18, 24, 30, or 36 months at 25° C., 1, 2, 3, 4, 5, or 6 months at 40° C., 1, 2, 4, 6, 8, or 12 weeks at 50° C., or 7, 14, or 21 days at 60° C. When stored at 25° C., the relative humidity may be, for example, 60% RH, and when stored at 40° C., the relative humidity may be 75% RH.

[0016] As used herein, "polymeric polysaccharides having methoxy groups and / or hydroxypropoxy groups on the cellulose backbone" refers to polymeric polysaccharides having methoxy groups (-OCH), hydroxypropoxy groups (-OCHOH), or a combination thereof as an ether structure on the cellulose backbone. Examples of "polymeric polysaccharides having methoxy groups and / or hydroxypropoxy groups on the cellulose backbone" as used herein include methylcellulose, hypromellose, hypromellose acetate succinate, hypromellose phthalate, and hydroxypropylcellulose, with methylcellulose or hypromellose being preferred. These polymeric polysaccharides having methoxy groups and / or hydroxypropoxy groups on the cellulose backbone can be used alone or in combination of two or more.

[0017] In this specification, "methylcellulose" refers to a cellulose derivative having a methoxy group in the cellulose skeleton, and various grades with different viscosities and degrees of methoxy group substitution exist. Methylcellulose of various grades with different viscosities and degrees of methoxy group substitution may be used alone or in combination of two or more. The viscosity of a 2% by mass aqueous solution of methylcellulose at 20° C. is preferably 1 to 18 mPa s. The viscosity of a 2% by mass aqueous solution of methylcellulose at 20° C. can be measured by the viscosity measurement method described in the section on “Methylcellulose” in the 18th Edition of the Japanese Pharmacopoeia. The degree of substitution of methoxy groups in methylcellulose can be expressed as the content of methoxy groups in methylcellulose. The content of methoxy groups in methylcellulose is preferably 25.0% by mass to 33.0% by mass. The content of methoxy groups in methylcellulose can be measured by the quantitative method described in the section on "Methylcellulose" in the 18th Edition of the Japanese Pharmacopoeia. Herein, "methylcellulose" may be referred to as "MC."

[0018] The methylcellulose referred to in this specification is a known compound and can be produced by known methods, or commercially available methylcellulose can be used. Examples of commercially available methylcellulose include METOLOSE SM (product name) manufactured by Shin-Etsu Chemical Co., Ltd., such as METOLOSE SM-4, METOLOSE SM-4VF, and METOLOSE SM-15 (methyl group substitution degree: 26.0 to 33.0%, nominal viscosity: 4, 4, and 15 mPa s, respectively), and METHOCEL Premium A (product name) manufactured by DuPont, such as METHOCEL A15 LV (methyl group substitution degree: 29%, nominal viscosity: 15 mPa s).

[0019] "Hypromellose" as used herein refers to a cellulose derivative having methoxy and hydroxypropoxy groups in the cellulose backbone, and is available in a variety of grades with different viscosities and degrees of substitution of methoxy and hydroxypropoxy groups. Hypromellose of various grades with different viscosities and degrees of substitution of methoxy and hydroxypropoxy groups can be used alone or in combination of two or more types. The viscosity of a 2% by mass aqueous solution of hypromellose at 20° C. is preferably 1 to 50 mPa s. The viscosity of a 2% by mass aqueous solution of hypromellose at 20° C. can be measured by the viscosity measurement method described in the section on "Hypromellose" in the 18th Edition of the Japanese Pharmacopoeia. The degree of substitution of methoxy or hydroxypropoxy groups in hypromellose can be expressed as the content of methoxy or hydroxypropoxy groups in hypromellose. The lower limit of the methoxy group content in hypromellose is, for example, 16.5% by mass or more, 19.0% by mass or more, 27.0% by mass or more, or 28.0% by mass or more, and the upper limit is 20.0% by mass or less, 24.0% by mass or less, or 30.0% by mass or less, preferably 16.5 to 30.0% by mass, more preferably 16.5 to 20.0% by mass, 19.0 to 24.0% by mass, 27.0 to 30.0% by mass, or 28.0 to 30.0% by mass. The hydroxypropoxy group content in hypromellose is, for example, 4.0% by mass or more, 7.0% by mass or more, or 23.0% by mass or more as a lower limit, and 32% by mass or less, 12.0% by mass or less, or 7.5% by mass or less as an upper limit, preferably 4.0 to 32.0% by mass, more preferably 23.0 to 32.0% by mass, 4.0 to 12.0% by mass, 4.0 to 7.5% by mass, or 7.0 to 12.0% by mass. The methoxy group and hydroxypropoxy group contents in hypromellose are preferably 16.5 to 20.0% by mass and 23.0 to 32.0% by mass, 19.0 to 24.0% by mass and 4.0 to 12.0% by mass, 27.0 to 30.0% by mass and 4.0 to 7.5% by mass, or 28.0 to 30.0% by mass and 7.0 to 12.0% by mass, respectively. More preferably, the degree of substitution of methoxy groups and hydroxypropoxy groups in hypromellose is a degree of substitution shown in the section on "hypromellose" of the Japanese Pharmacopoeia, 18th Edition, as substitution type 1828, 2208, 2906, or 2910. The content of hydroxypropoxy groups and the content of methoxy groups in hypromellose can be measured by the quantitative method described in the section on "hypromellose" of the Japanese Pharmacopoeia, 18th Edition. Herein, "hypromellose" may be referred to as "HPMC" or "hydroxypropyl methylcellulose."

[0020] The hypromellose used herein is a known compound and can be produced by known methods, or commercially available products can be used. Examples of commercially available hypromellose include those manufactured by Shin-Etsu Chemical Co., Ltd. under the trade name TC-5, such as TC-5E, TC-5M, TC-5R, and TC-5S (degree of substitution type: 2910, nominal viscosity: 3, 4.5, 6, and 15 mPa·s, respectively); and those manufactured by DuPont under the trade name METHOCEL Premium E, F, or K, such as METHOCEL E3LV, METHOCEL E5LV, METHOCEL E6LV, and METHOCEL E15LV (degree of substitution type: 2910, nominal viscosity: 3, 5, 6, and 15 mPa·s, respectively), METHOCEL VLV, METHOCEL F4LV, and METHOCEL F5LV (degree of substitution type: 2906, nominal viscosity: 2.8, 4, and 5 mPa·s, respectively), and METHOCEL K3LV (nominal viscosity: 3 mPa·s, degree of substitution type: 2208).

[0021] "Polyvinyl alcohol" as used herein refers to a polymer obtained by saponifying polyvinyl acetate and can be represented by -(CHCHOH)-. Polyvinyl alcohol is available in various grades with different degrees of saponification and viscosities. Various grades of polyvinyl alcohol with different degrees of saponification and viscosities can be used alone or in combination of two or more types. The degree of saponification of polyvinyl alcohol is, for example, 70 mol% or more, 75 mol% or more, 78 mol% or more, 85 mol% or more, 92 mol% or more, 98 mol% or more, or 99 mol% or more as a lower limit, and 100 mol% or less, 99 mol% or less, 98 mol% or less, 96 mol% or less, 90 mol% or less, 89 mol% or less, 85 mol% or less, or 75 mol% or less, preferably 70 to 100 mol%, more preferably 78 to 96 mol%, 92 to 98 mol%, or 98 to 100 mol%, particularly preferably 85 to 89 mol%. The degree of saponification of polyvinyl alcohol can be measured by the saponification degree measurement method described in the section "Polyvinyl alcohol (fully saponified)" or "Polyvinyl alcohol (partially saponified)" of the Pharmaceutical Excipients Standards 2018. The viscosity of a 4% by mass aqueous solution of polyvinyl alcohol at 20°C is, for example, 2 mm 2 / s or more, 4mm 2 / s or more, 10mm 2 / s or more, 20mm 2 / s or more or 40 mm 2 / s or more, with an upper limit of 60 mm 2 / s or less, 40mm 2 / s or less, 25mm 2 / s or less, 10mm 2 / s or less or 6 mm 2 / s or less, preferably 2 to 60 mm 2 / s, preferably 2 to 6 mm 2 / s, 4~10mm 2 / s, 10~25mm 2 / s, 20~40mm 2 / s or 40-60mm 2 The viscosity of polyvinyl alcohol can be measured by the viscosity measurement method described in the section on "Polyvinyl alcohol (fully saponified)" or "Polyvinyl alcohol (partially saponified)" of the Pharmaceutical Excipients Standards 2018. Polyvinyl alcohol with a degree of saponification of 97 mol% or more may also be called "polyvinyl alcohol (fully saponified)". Polyvinyl alcohol with a degree of saponification of 78 to 96 mol% may also be called "polyvinyl alcohol (partially saponified)" and may be represented by -(CH2CHOH)n-(CH2CHOCOCH3)m-. Herein, "polyvinyl alcohol" may be referred to as "PVA."

[0022] The polyvinyl alcohol in this specification is a known compound and can be produced by known methods, or commercially available products can be used. Examples of commercially available polyvinyl alcohol include Gohsenol EG, a trade name of Mitsubishi Chemical Corporation, such as Gohsenol EG-03P, Gohsenol EG-05P, and Gohsenol EG-05PW (all of which have a degree of saponification of 86.5 to 89.0 mol%, a viscosity of 3.0 to 6.1 mm). 2 / s) and PE-05JPS (saponification degree: 85 to 89 mol%, viscosity: 4.6 to 6.0 mPa·s) manufactured by Nippon Vinyl Acetate & Poval Co., Ltd.

[0023] In one embodiment, the present invention provides a coated preparation in which a core is coated with two or more coating layers, wherein the two or more coating layers are: (1) A coating layer A including a coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol is 0.1:1 to 3:1; and (2) Coating layer B containing a coating base containing methylcellulose The present invention includes a formulation comprising:

[0024] The mass of the core in the coated formulation of the present invention may be any amount that does not interfere with administration, and in one embodiment, when the core is a tablet (plain tablet), the mass of the core in the coated formulation of the present invention may be, for example, at least 25 mg, at least 50 mg, or at least 70 mg as a lower limit, and at most 1000 mg, at most 800 mg, or at most 500 mg as an upper limit, and may be, for example, 25 to 1000 mg, preferably 50 to 800 mg, and more preferably 70 to 500 mg.

[0025] The coating layer A of the present invention comprises a coating base containing (a) a polymeric polysaccharide having methoxy and / or hydroxypropoxy groups in its cellulose skeleton, and (b) polyvinyl alcohol. The ratio (a:b) of (a) the polymeric polysaccharide having methoxy and / or hydroxypropoxy groups in its cellulose skeleton to (b) the polyvinyl alcohol in the coating layer A is, for example, at least 0.1:1, at least 0.3:1, at least 0.5:1, or at least 1:1, and at most 5:1 or at most 3:1, for example, 0.1:1 to 5:1, preferably 0.1:1 to 3:1, and more preferably 0.3:1 to 3:1.

[0026] The amount of the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton contained in coating layer A relative to the mass of the core may be, for example, at least 0.1%, at least 0.5%, or at least 1%, and at most 30%, at most 20%, at most 10%, or at most 5%, for example, 0.1 to 30%, preferably 0.5 to 10% or 1 to 20%, and more preferably 1 to 5%. When the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton is methylcellulose, the amount of methylcellulose contained in coating layer A relative to the mass of the core may be, for example, at least 0.1%, at least 0.5%, or at least 1% as a lower limit, and at most 30%, at most 20%, at most 10%, or at most 5% as an upper limit, for example, 0.1 to 30%, preferably 0.5 to 10% or 1 to 20%, and more preferably 1 to 5%. When the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton is hypromellose, the amount of hypromellose contained in coating layer A relative to the mass of the core may be, for example, at least 0.1%, at least 0.5%, or at least 1% as a lower limit, and at most 30%, at most 20%, at most 10%, or at most 5% as an upper limit, for example, 0.1 to 30%, preferably 0.5 to 10% or 1 to 20%, and more preferably 1 to 5%. When the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups in the cellulose skeleton is a mixture of methylcellulose and hypromellose, the amount of the mixture of methylcellulose and hypromellose contained in coating layer A relative to the mass of the core may be, for example, at least 0.1%, at least 0.5%, or at least 1% as a lower limit, and at most 30%, at most 20%, at most 10%, or at most 5% as an upper limit, for example, 0.1 to 30%, preferably 0.5 to 10% or 1 to 20%, and more preferably 1 to 5%.

[0027] The amount of polyvinyl alcohol contained in coating layer A relative to the mass of the core may be, for example, at least 0.1%, at least 0.5%, or at least 1% as a lower limit, and at most 30%, at most 20%, at most 10%, or at most 5% as an upper limit, for example, 0.1 to 30%, preferably 0.5 to 10% or 1 to 20%, and more preferably 1 to 5%.

[0028] The coating layer A may contain components other than the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in the cellulose skeleton and polyvinyl alcohol, such as a coating base, a plasticizer, a fluidizing agent, a colorant, a light-blocking agent, a flavoring agent, etc., as long as the effects of the present invention are not impaired.

[0029] Examples of plasticizers include copolyvidone, polyethylene glycol, triethyl citrate, castor oil, and polysorbate. Examples of the fluidizing agent include light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, magnesium silicate, magnesium aluminometasilicate, and talc. Examples of coloring agents or light-blocking agents include titanium oxide, yellow ferric oxide, ferric oxide, and riboflavin. Examples of flavoring agents include ascorbic acid, erythritol, citric acid, tartaric acid, malic acid, sucralose, and stevia extract.

[0030] The coating layer B in the present invention contains a coating base containing methylcellulose. The amount of methylcellulose contained in coating layer B may be, for example, a lower limit of 0.8% or more and an upper limit of 20% or less, 10% or less, or 5% or less, preferably 0.8 to 20% or 0.8 to 10%, more preferably 0.8 to 5%, relative to the mass of the core.

[0031] The coating layer B may contain components other than methylcellulose, such as a coating base, a plasticizer, a fluidizing agent, a colorant, a light-blocking agent, a flavoring agent, etc., as long as the effects of the present invention are not impaired. The plasticizer, fluidizing agent, colorant, light-blocking agent and flavoring agent that may be contained in coating layer B are the same as those described above for coating layer A.

[0032] Herein, "coating layer A" may be referred to as "layer A." Also, herein, "coating layer B" may be referred to as "layer B."

[0033] The order of the two or more coating layers in the present invention is not particularly limited, and the core may be coated with Layer A, and Layer A may be coated with Layer B (i.e., Layer A is the inner layer and Layer B is the outer layer), or the core may be coated with Layer B, and Layer B may be coated with Layer A (i.e., Layer A is the outer layer and Layer B is the inner layer). The two or more coating layers in the present invention may have an additional layer in addition to Layer A and Layer B. The additional layer may be present between Layer A and Layer B, between the plain tablet and Layer A or Layer B, or on the outside of Layers A and B.

[0034] The additional layer includes, for example, a coating base, a plasticizer, a fluidizing agent, a colorant, a light-blocking agent, etc. The plasticizer, fluidizing agent, colorant, and light-blocking agent that can be included in the additional layer are the same as those described for coating layer A above. Examples of coating bases include water-soluble bases such as hydroxypropyl methylcellulose (hypromellose), hydroxypropyl cellulose, methylcellulose, povidone, copolyvidone, polyvinyl alcohol, polyvinyl alcohol copolymers, and macrogol; water-insoluble bases such as ethyl cellulose; enteric bases such as hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymers, acrylic acid copolymers, and carboxyvinyl polymers; gastrosoluble bases such as polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymers, and polyvinyl acetate diethylaminoacetate; gum arabic, pullulan, carnauba wax, shellac, macrogols, glycerin fatty acid esters, and magnesium stearate.

[0035] The total amount of coating base contained in coating layer A and coating layer B, preferably the total amount of coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in the cellulose skeleton, polyvinyl alcohol, and methylcellulose contained in coating layer A and coating layer B, relative to the mass of the core, can be, for example, at least 4% or at least 5% as a lower limit and at most 40%, at most 20%, or at most 15% as an upper limit, for example, 4 to 40%, preferably 4 to 15% or 5 to 20%, and more preferably 5 to 15%.

[0036] Herein, the amount of each coating base in a coating formulation can be determined, for example, by subtracting the mass of the formulation before coating, i.e., the mass of the core, from the mass of the formulation after coating with the coating layer.

[0037] In one embodiment of the present invention, the core comprises vitamin B1 and nicotinic acid. In another embodiment of the present invention, the core comprises vitamin B1, nicotinic acid and herbal medicine or an extract thereof.

[0038] The "core" in this specification may contain active ingredients other than vitamin B1, nicotinic acids, and herbal medicines or extracts thereof, and additives, as long as they do not inhibit the effects of the present invention.

[0039] As used herein, vitamin B1 refers to thiamine. The term "vitamins B1" as used herein encompasses vitamin B1, its derivatives, and salts thereof. Examples of "vitamins B1" as used herein include thiamine, bisthiamine, thiamine disulfide, dicethiamine, fursultiamine, octotiamine, sicotiamine, bis-ibutiamine, bis-bentiamine, prosultiamine, and benfotiamine, as well as salts thereof. Examples of such salts include inorganic acid salts such as hydrochloride, nitrate, nitrate, and sulfate. Vitamin B1 derivatives or salts thereof may be in the form of solvates (e.g., hydrates). In this specification, "vitamin B1" preferably refers to thiamine, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, dicethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, shikotiamine, bis-ibutiamine, bis-bentiamine, prosultiamine, or benfotiamine, more preferably fursultiamine or a salt thereof, particularly preferably fursultiamine or fursultiamine hydrochloride. These vitamin B1s may be used alone or in combination of two or more. These vitamin B1 compounds are known compounds and can be produced by known methods, or commercially available products can be used. The amount of vitamin B1 contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1 mass% or more, 0.3 mass% or more, or 0.5 mass% or more, and an upper limit of 50 mass% or less, 40 mass% or less, or 20 mass% or less, relative to the entire solid preparation, and may be, for example, 0.1 to 50 mass%, preferably 0.3 to 40 mass%, and more preferably 0.5 to 20 mass%.

[0040] As used herein, "nicotinic acids" encompass nicotinic acid, its derivatives, and salts thereof. Examples of "nicotinic acids" as used herein include nicotinic acid, nicotinamide, nicotinic acid esters (e.g., nicotinic acid methyl ester, nicotinic acid β-butoxyethyl ester, nicotinic acid benzyl ester, inositol hexanicotinate, and hepronicate), nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate, as well as salts thereof. Examples of such salts include alkali metal salts such as sodium salts. As used herein, nicotinic acid and nicotinamide are collectively referred to as "niacin." As used herein, "nicotinic acids" are preferably nicotinic acid, nicotinamide, niacin, sodium nicotinate, or nicotinic acid methyl ester, more preferably nicotinic acid, nicotinamide, or niacin, and particularly preferably nicotinamide. These nicotinic acids may be used alone or in combination. These nicotinic acids are known compounds and can be produced by known methods, or commercially available products can be used. The amount of nicotinic acids contained in the solid preparation of the present invention is not particularly limited, and may be, for example, a lower limit of 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, and an upper limit of 50% by mass or less, 40% by mass or less, or 25% by mass or less, relative to the entire solid preparation, and may be, for example, 0.1 to 50% by mass, preferably 0.5 to 40% by mass, and more preferably 1 to 25% by mass.

[0041] The ratio of vitamin B1 class and nicotinic acids contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1 part by mass or 1 part by mass or more of nicotinic acids per 1 part by mass of vitamin B1 class, and an upper limit of 20 parts by mass or 10 parts by mass or less, for example, 0.1 to 20 parts by mass, preferably 0.1 to 10 parts by mass or 1 to 20 parts by mass. The total amount of vitamin B1 class and nicotinic acids contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, and an upper limit of 50% by mass or less, 40% by mass or less, or 25% by mass or less, for example, 0.1 to 50% by mass, preferably 0.5 to 40% by mass, and more preferably 1 to 25% by mass.

[0042] In this specification, the herbal medicines may be in the form of bulk drugs, chopped or cut herbal medicines, or powdered herbal medicines. "Chopped herbal medicines" or "cut herbal medicines" refer to whole herbal medicines that have been cut or crushed into small pieces or chunks, or roughly, medium, or finely chopped, while "powdered herbal medicines" refer to whole or cut herbal medicines that have been made into coarse, medium, fine, or fine powders. In this specification, powdered herbal medicines made by powdering herbal medicines such as Astragalus Root and Shigoka may be referred to as Astragalus Root powder, Shigoka powder, etc.

[0043] As used herein, "herbal extract" refers to a product obtained by subjecting herbal medicines to extraction processing and contains extracted components of the herbal medicines. Herbal extracts can be obtained by conventional methods, for example, by extracting raw materials using an extraction solvent at an appropriate temperature (low temperature or high temperature). The extraction solvent can be selected appropriately, for example, water, a hydrophilic solvent, or a mixture thereof. Ethanol is preferably used as the hydrophilic solvent. The herbal extract may be a liquid extract as is, a liquid extract diluted with water, a liquid extract concentrate, or a liquid extract dried. Therefore, as used herein, "herbal extract" includes liquid extracts, extracts, dried extracts, extract powders, soft extracts, liquid extracts, tinctures, etc.

[0044] In this specification, the amount of a herbal medicine or its extract may be expressed in terms of the amount of the original herbal medicine. In addition, when the herbal medicine extract is a liquid extract or a liquid extract diluted with a solvent such as water, the amount may be expressed in terms of mass.

[0045] The total amount of herbal medicines or extracts thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 1% by mass or more, 10% by mass or more, or 20% by mass or more, and an upper limit of 250% by mass or less, 200% by mass or less, 150% by mass or less, or 100% by mass or less, and may be, for example, 1 to 250% by mass, preferably 1 to 200% by mass, in terms of the amount of crude herbal medicine relative to the entire solid preparation. Furthermore, the total amount of herbal medicines or extracts thereof contained in the solid preparation of the present invention is not particularly limited, but when each herbal medicine is an extract, for example, the lower limit may be 0.5% by mass or more, 1% by mass or more, or 3% by mass or more, and the upper limit may be 50% by mass or less, 30% by mass or less, or 20% by mass, and may be, for example, 0.5 to 50% by mass, preferably 1 to 30% by mass, and more preferably 3 to 20% by mass. Furthermore, the total amount of herbal medicines or extracts thereof contained in the solid preparation of the present invention is not particularly limited, but when each herbal medicine is in the form of bulk powder, for example, the lower limit may be 1% by mass or more, 3% by mass or more, or 5% by mass or more, and the upper limit may be 50% by mass or less, 30% by mass or less, or 20% by mass, and may be, for example, 1 to 50% by mass, preferably 3 to 30% by mass, and more preferably 5 to 20% by mass. The total amount of the herbal medicine or extract thereof contained in the solid preparation of the present invention is not particularly limited, but when the herbal medicine contains a combination of an extract and bulk powder, for example, the lower limit is 1% by mass or more, 5% by mass or more, or 10% by mass or more, and the upper limit is 80% by mass or less, 50% by mass or less, or 30% by mass, and can be, for example, 1 to 80% by mass, preferably 5 to 50% by mass, and more preferably 10 to 30% by mass.

[0046] Examples of "crude drugs or extracts thereof" in the present specification include Mallotus japonicus, Acacia japonica, Hydrangea tea, Gum arabic, Aloe vera, Anthocephalum chinensis, Irei saffron, Inchinko, Echinacea chinensis, Fennel, Turmeric, Uva-ursi, Atractylodes oryzae, Corydalis chinensis, Astragalus chinensis, Scutellaria baicalensis, Phellodendron bark, Coptis chinensis, Onion root, Spirea chinensis, Kagosou, Zedoary, Cuckoo Root, Pueraria lobata, Kasseki, Valerian, Kalocornis chinensis, Kankyo, Glycyrrhiza uralensis, Agar, Platycodon grandiflorum, Chrysanthemum chrysanthemum, Catalpa, Phellodendron chinensis, and Kyo. Cutlet, Chinese laurel, Goji berry, Sophora root, Cabbage, Cinnamon bark, Cassia japonica, Kengoshi, Gentian, Gentiana japonica, Koi, Kouka, Kojin, Kobushi, Kobei, Kobo, Goshitsu, Goshuyu, Burdock, Sesame, Gomizushi, Colombo, Condoranguo, Bupleurum, Spice, Saffron, Japanese hawthorn, Japanese hawthorn, Chinese holly, Japanese pepper, Chinese holly, Dioscorea chinensis, Rehmannia glutinosa, Japanese holly, Lithospermum root, Chinese holly, Shakanzo, Peony, Jasmine berry, Chinese holly, Chinese holly, Chinese herb, Kusha, Ginger, Cardamom, Ginseng, Shini, Shingi, Sekko, Senega, Cnidium, Zenko, Senkotsu, Senso, Senna, Swertia, Soju, Sohakuhi, Sobok, Soybean, Rhubarb, Chinese Root, Salvia, Salvia officinalis, Salvia serrata, Salvia miltiorrhiza, Salvia serrata ... Examples of such herbs include moth, rhododendron, honey, mint, litchi thunbergii, radix serrata, white gourd, angelica chinensis, white atractylodes, locust, betel nut, poria cocos, bush clover, belladonna cone, henzu, bowie, scutellaria baicalensis, scutellaria baicalensis, bokufu, moutan pi, vomica, bolei, ephedra, makuri, mashinin, scutellaria baicalensis, mukko, yakuchi, yakumosou, yutan, coix seed, longan nut, scutellaria baicalensis, rhubarb, rye, forsythia, lotus fruit, rosin, scopolia cone, royal jelly, joteishu, and extracts thereof.Preferably, the "herbal medicine or an extract thereof" herein is selected from Astragalus Root, Shigoka Root, Ginseng, Eucommia Root, Peony Root, Poria Cocos, Dioscorea Root, Cinnamon Bark, Lycium Fruit, Atractylodes Rhizome, Fennel, Astragalus Root, Licorice Root, Chinese Cabbage, Licorice Root, Cinnamon Bark, Cistanche Salicylate, and Longan Fruit, and extracts thereof. Preferably, the "herbal medicine or an extract thereof" herein is selected from Astragalus Root, Shigoka Root, Ginseng, Eucommia Root, Peony Root, Poria Cocos, Dioscorea Root, Cinnamon Bark, Lycium Fruit, and Atractylodes Rhizome, and extracts thereof.

[0047] As used herein, "Astragalus membranaceus Bunge" refers to the root of Astragalus membranaceus Bunge or Astragalus mongholicus Bunge (Leguminosae). Astragalus Root or an extract thereof is a known herbal medicine or an extract thereof, and can be produced by a known method or commercially available products can be used. Preferably, Astragalus Root listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of Astragalus membranaceus or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 1% by mass or more and an upper limit of 200% by mass or less or 100% by mass or less, for example, 0.1 to 200% by mass, preferably 1 to 100% by mass, in terms of the amount of crude drug relative to the entire solid preparation. The amount of Astragalus membranaceus or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 20% by mass or less as the upper limit, for example, 0.1 to 20% by mass, preferably 1 to 10% by mass, based on the total mass of the solid preparation.

[0048] "Shigoka" as used herein refers to the rhizome, often accompanied by roots, of Eleutherococcus senticosus Maximowicz (Acanthopanax senticosus Harms) (Araliaceae). "Shigoka" as used herein may also be referred to as "Eleutherococcus senticosus." Shigoka or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, Shigoka listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of Schizosaccharum or an extract thereof contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 1% by mass or more, and an upper limit of 400% by mass or less or 300% by mass or less, and may be, for example, 0.1 to 400% by mass, preferably 1 to 300% by mass, in terms of the amount of the crude drug relative to the entire solid formulation. The amount of Schizosaccharum or an extract thereof contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass as a lower limit and 50% by mass or less or 30% by mass or less, for example, 0.1 to 50% by mass, preferably 1 to 30% by mass, relative to the entire solid formulation.

[0049] "Ginseng" in this specification refers to the root of Panax ginseng CA Meyer (Panax schinseng Nees) (Araliaceae) with the fine roots removed or lightly blanched. Preferably, when quantifying ginseng, the content of ginsenoside Rg1 (C 42 H 72 O 14 :801.01) 0.10% or more and ginsenoside RB1 (C 54 H 92 O 23 :1109.29) Contains 0.20% or more. Ginseng or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, ginseng or ginseng powder listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of ginseng or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 1% by mass or more or 10% by mass or more, and an upper limit of 700% by mass or less or 500% by mass or less, and may be, for example, 1 to 700% by mass, preferably 10 to 500% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of ginseng or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount can be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 50% by mass or less or 40% by mass or less as the upper limit, for example, 0.1 to 50% by mass, preferably 1 to 40% by mass, relative to the entire solid preparation.

[0050] "Eucommia" in this specification refers to the bark of Eucommia ulmoides Oliver (Eucommiaceae). Eucommia or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, Eucommia listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of Eucommia or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 100% by mass or less or 75% by mass or less, expressed as the amount of the crude drug relative to the entire solid preparation, and may be, for example, 0.01 to 100% by mass, preferably 0.1 to 75% by mass. The amount of Eucommia or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.001% by mass or more or 0.01% by mass or more as the lower limit and 30% by mass or less or 15% by mass or less as the upper limit, for example, 0.001 to 30% by mass, preferably 0.01 to 15% by mass, relative to the entire solid preparation.

[0051] The term "peony" as used herein refers to the root of Paeonia lactiflora Pallas (Paeoniaceae). Preferably, when quantifying peony, the content of paeoniflorin (C 23 H 28 O 11 :480.46) Contains 2.0% or more. Peony or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, peony or peony powder listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of peony or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 80% by mass or less or 50% by mass or less, expressed as the amount of crude drug relative to the entire solid preparation, and may be, for example, 0.01 to 80% by mass, preferably 0.1 to 50% by mass. The amount of peony or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 20% by mass or less or 10% by mass or less as the upper limit, for example, 0.1 to 20% by mass, preferably 1 to 10% by mass, relative to the entire solid preparation.

[0052] In this specification, "pokryo" refers to the sclerotium of Wolfiporia cocos Ryvarden et Gilbertson (Poria cocos Wolf) (Polyporaceae), usually with most of the outer layer removed. Poria cocos or an extract thereof is a known herbal medicine or an extract thereof, and can be produced by a known method or commercially available products can be used. Preferably, Poria cocos or Poria cocos powder listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of Poria cocos or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more and an upper limit of 150% by mass or less or 100% by mass or less, and may be, for example, 0.01 to 150% by mass, preferably 0.1 to 100% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of Poria cocos or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 30% by mass or less or 20% by mass or less as the upper limit, for example, 0.1 to 30% by mass, preferably 1 to 20% by mass, relative to the entire solid preparation.

[0053] In this specification, "Sanyaku" refers to the rhizome (rhizophore) of Dioscorea japonica Thunberg (Japanese yam) or Dioscorea batatas Decaisne (Dioscoreaceae) from which the periderm has been removed. The dioscorea root or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the dioscorea root or dioscorea root powder listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of Dioscorea or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 200% by mass or less or 150% by mass or less, for example, 0.01 to 200% by mass, preferably 0.1 to 150% by mass, in terms of the amount of raw herbal medicine relative to the entire solid formulation. The amount of Dioscorea or its extract contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 80% by mass or less or 50% by mass or less as the upper limit, for example, 0.1 to 80% by mass, preferably 1 to 50% by mass, relative to the entire solid formulation.

[0054] "Cinnamon" in this specification refers to the bark or bark of Cinnamomum cassia J. Presl (Lauraceae) excluding a portion of the periderm. "Cinnamon oil" in this specification refers to an essential oil obtained by steam distillation of the leaves, twigs, or bark of Cinnamomum cassia J. Presl or the bark of Cinnamomum zeylanicum Nees (Lauraceae). Preferably, the cinnamon oil contains 60 vol% or more of total aldehydes when quantified. Cinnamon bark or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, cinnamon bark, cinnamon powder, or cinnamon oil listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of cinnamon or its extract contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 1% by mass or more, and an upper limit of 80% by mass or less or 50% by mass or less, for example, 0.1 to 80% by mass, preferably 1 to 50% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of cinnamon or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount can be, for example, 0.01% by mass or more or 0.1% by mass or more as the lower limit and 20% by mass or less or 10% by mass or less as the upper limit, for example, 0.01 to 20% by mass, preferably 0.1 to 10% by mass, relative to the entire solid preparation.

[0055] "Lycium chinense" as used herein refers to the fruit of wolfberry Lycium chinense Miller or Lycium barbarum Linne (Solanaceae). Lycium chinense or an extract thereof is a known herbal medicine or an extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, Lycium chinense listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of lycium bark or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 1% by mass or more, and an upper limit of 400% by mass or less or 350% by mass or less, for example, 0.1 to 400% by mass, preferably 1 to 350% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of lycium bark or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 1% by mass or more or 2% by mass or more as the lower limit and 80% by mass or less or 50% by mass or less as the upper limit, for example, 1 to 80% by mass, preferably 2 to 50% by mass, relative to the entire solid preparation.

[0056] "Shuksha" as used herein refers to the seed masses of Amomum villosum Loureiro var. xanthioides TL Wu et SJ Chen, Amomum villosum Loureiro var. villosum or Amomum longiligulare TL Wu (Zingiberaceae). The Shakusha or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the Shakusha or Shakusha powder listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of Atractylodes or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 200% by mass or less or 100% by mass or less, and may be, for example, 0.01 to 200% by mass, preferably 0.1 to 100% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of Atractylodes or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 50% by mass or less or 25% by mass or less as the upper limit, for example, 0.1 to 50% by mass, preferably 1 to 25% by mass, relative to the entire solid preparation.

[0057] "Fennel" herein is the fruit of Foeniculum vulgare Miller (Umbelliferae). Fennel or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, fennel or fennel powder listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of fennel or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 80% by mass or less or 60% by mass or less, expressed as the amount of the crude drug relative to the entire solid formulation, and may be, for example, 0.01 to 80% by mass, preferably 0.1 to 60% by mass. The amount of fennel or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, a lower limit of 0.001% by mass or more or 0.01% by mass or more, and an upper limit of 50% by mass or less or 40% by mass or less, relative to the entire solid preparation, and may be, for example, 0.001 to 50% by mass, preferably 0.01 to 40% by mass.

[0058] In this specification, "Ousei" refers to the rhizomes of Polygonatum kingianum Collett et Hemsley, Polygonatum sibiricum Redoute, Polygonatum cyrtonema Hua, or Polygonatum falcatum A. Gray (Liliaceae), which are typically steamed. The herb or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the herb listed in the 18th Edition of the Japanese Pharmacopoeia can be used. The amount of ginseng or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 0.5% by mass or more, and an upper limit of 500% by mass or less or 400% by mass or less, in terms of the amount of raw herbal medicine relative to the entire solid formulation, and may be, for example, 0.1 to 500% by mass, preferably 0.5 to 400% by mass. The amount of herbal extract or its extract contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 80% by mass or less or 60% by mass or less as the upper limit, for example, 0.1 to 80% by mass, preferably 1 to 60% by mass, relative to the entire solid formulation.

[0059] "Joteishi" as used herein refers to the fruit of Ligustrum lucidum WT Aiton or Ligustrum japonicum Thunberg (Oleaceae). The Jotei-shi or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the Jotei-shi listed in the Japanese Pharmacopoeia Extra-Catalog of Crude Drugs 2022 can be used. The amount of Joyeuse or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but may be, for example, a lower limit of 1% by mass or more or 2% by mass or more and an upper limit of 400% by mass or less or 200% by mass or less, for example, 1 to 400% by mass, preferably 2 to 200% by mass, in terms of the amount of the crude drug relative to the entire solid preparation. The amount of Jotei-shi or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.1% by mass or more or 1% by mass or more as the lower limit and 80% by mass or less or 50% by mass or less as the upper limit, for example, 0.1 to 80% by mass, preferably 1 to 50% by mass, relative to the entire solid preparation.

[0060] "Taiso" in this specification refers to the fruit of Ziziphus jujuba Miller var. inermis Rehder (Rhamnaceae). The ginseng or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the ginseng listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of ginseng or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 1% by mass or more, and an upper limit of 150% by mass or less or 100% by mass or less, in terms of the amount of the crude drug relative to the entire solid formulation, for example, 0.1 to 150% by mass, preferably 1 to 100% by mass. The amount of ginseng or its extract contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the lower limit is, for example, 0.01% by mass or more or 0.1% by mass or more, and the upper limit is 80% by mass or less or 50% by mass or less, relative to the entire solid formulation, and can be, for example, 0.01 to 80% by mass, preferably 0.1 to 50% by mass.

[0061] "Chinpi" as used herein is the mature pericarp of Citrus unshiu Markowicz or Citrus reticulata Blanco (Rutaceae). The tangerine peel or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, the tangerine peel listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of Tangerine Peel or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 150% by mass or less or 100% by mass or less, expressed as the amount of raw herbal medicine relative to the entire solid formulation, and may be, for example, 0.01 to 150% by mass, preferably 0.1 to 100% by mass. The amount of Tangerine Peel or an extract thereof contained in the solid preparation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, a lower limit of 0.001% by mass or more or 0.01% by mass or more, and an upper limit of 80% by mass or less or 50% by mass or less, relative to the entire solid preparation, for example, 0.001 to 80% by mass, preferably 0.01 to 50% by mass.

[0062] As used herein, "Cistanche salsa" refers to the fleshy stem of 1) Cistanche salsa G. Beck, 2) Cistanche deserticola YC Ma, or 3) Cistanche tubulosa Wight (Orobanchaceae), excluding the inflorescence when in flower. Cistanche salsa or an extract thereof is a known herbal medicine or an extract thereof, and can be produced by a known method or commercially available products can be used. Preferably, Cistanche salsa listed in the 18th revised Japanese Pharmacopoeia can be used. The amount of Cistanche salicina or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.1% by mass or more or 0.5% by mass or more, and an upper limit of 500% by mass or less or 400% by mass or less, and may be, for example, 0.1 to 500% by mass, preferably 0.5 to 400% by mass, in terms of the amount of crude drug relative to the entire solid formulation. The amount of Cistanche salicylate or its extract contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.5% by mass or more or 1% by mass or more as the lower limit and 50% by mass or less or 30% by mass or less as the upper limit, for example, 0.5 to 50% by mass, preferably 1 to 30% by mass, relative to the entire solid formulation.

[0063] "Longannik" as used herein refers to the arils of Euphoria longana Lamarck (Sapindaceae). Longan Root or its extract is a known herbal medicine or extract thereof, and can be produced by known methods or commercially available products can be used. Preferably, longan Root listed in the 18th Revised Japanese Pharmacopoeia can be used. The amount of longan berry or its extract contained in the solid formulation of the present invention is not particularly limited, but may be, for example, a lower limit of 0.01% by mass or more or 0.1% by mass or more, and an upper limit of 150% by mass or less or 100% by mass or less, in terms of the amount of raw herbal medicine relative to the entire solid formulation, and may be, for example, 0.01 to 150% by mass, preferably 0.1 to 100% by mass. The amount of longan berry or its extract contained in the solid formulation of the present invention is not particularly limited, but in the case of a herbal extract, the amount may be, for example, 0.001% by mass or more or 0.01% by mass or more as the lower limit and 80% by mass or less or 50% by mass or less as the upper limit, for example, 0.001 to 80% by mass, preferably 0.01 to 50% by mass, relative to the entire solid formulation.

[0064] In the solid formulation of the present invention, the above-mentioned herbal medicines or extracts thereof can be used alone or in combination of two or more. The "herbal medicines or extracts thereof" in the present invention are, for example, at least one selected from Astragalus Root, Shigoka Root, Ginseng, Eucommia Root, Peony Root, Poria Cocos, Dioscorea Root, Cinnamon Bark, Lycium Fruit, Atractylodes Rhizome, Fennel, Astragalus Root, Licorice Root, Rhizome Root, Cistanche Peel, Cistanche Salicylate, and Longan Fruit, and extracts thereof. The "herbal medicines or extracts thereof" in the present invention are, for example, at least one selected from Astragalus Root, Shigoka Root, Ginseng, Eucommia Root, Peony Root, Poria Cocos, Dioscorea Root, Cinnamon Bark, Lycium Fruit, and Atractylodes Rhizome, and extracts thereof.

[0065] The coating preparation or core of the present invention may contain active ingredients other than the above vitamin B1s, nicotinic acids, and herbal medicines or extracts thereof, such as antipyretics, analgesics, rhinitis medications, antihistamines, antitussives, expectorants, bronchodilators, gastric mucosa protecting agents, caffeines, vitamins, hypnotics and sedatives, phlegm dissolving agents, anti-inflammatory agents, anticholinergic agents, Chinese herbal medicine prescriptions, etc., as long as the effects of the present invention are not inhibited.

[0066] Examples of antipyretic analgesics include aspirin (acetylsalicylic acid), aluminum aspirin, acetaminophen, ibuprofen, salicylamide, sodium salicylate, ethenzamide, sazapyrine, lactylphenetidine, ketoprofen, isopropylantipyrine, and loxoprofen sodium. Examples of drugs for rhinitis include pseudoephedrine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, belladonna total alkaloids, isopropamide iodide, and dipotassium glycyrrhizinate. Examples of antihistamines include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, alimemazine tartrate, isothipendyl hydrochloride, promethazine methylenedisalicylate, diphenylpyraline hydrochloride, diphenylpyraline teoclate, difeterol hydrochloride, difeterol phosphate, triprolidine hydrochloride hydrate, tripelennamine hydrochloride, thondylamine hydrochloride, fenethazine hydrochloride, methdilazine hydrochloride, carbinoxamine diphenyldisulfonate, mebhydroline napadisilate, carbinoxamine maleate, iproheptine hydrochloride, promethazine hydrochloride, alimemazine tartrate, fenethazine tannate, clemastine fumarate, and mequitazine. Examples of narcotic antitussives include codeine phosphate hydrate, dihydrocodeine phosphate, etc. Examples of non-narcotic antitussives include alloclamide, isoaminil, eprazinone, oxeladin, clofedanol, clobutinol, cloperastine, dibunate, dimemorfan, tipepidine, dextromethorphan, noscapine, hydrocotalnin, pentoxyverine, benproperine, and fominoben, as well as salts and hydrates thereof. Examples of salts and hydrates thereof include alloclamide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, dibunate sodium, dimemorfan phosphate, tipepidine hibenzate, tipepidine citrate, dextromethorphan hydrobromide, dextromethorphan phenolphthalin salt, pentoxyverine citrate, and hydrates thereof. Examples of expectorants include potassium guaiacolsulfonate, bromhexine hydrochloride, guaifenesin, tipepidine citrate, L-carbocysteine, ammonium chloride, l-menthol, ammonia-fennel extract, and potassium cresolsulfonate. Examples of bronchodilators include dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, trimetoquinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, l-methylephedrine hydrochloride, pseudoephedrine hydrochloride, aminophylline, diprophylline, theophylline, and proxyphylline. Examples of gastric mucosa protective agents include glycine, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dried aluminum hydroxide gel, aluminum hydroxide-magnesium carbonate mixed dried gel, co-precipitation product of aluminum hydroxide-sodium bicarbonate, co-precipitation product of aluminum hydroxide-calcium carbonate-magnesium carbonate, co-precipitation product of magnesium hydroxide-aluminum potassium sulfate, and magnesium carbonate. Examples of caffeine compounds include sodium caffeine benzoate, caffeine hydrate, and anhydrous caffeine. Vitamins include, for example, vitamin B2 or a derivative thereof or a salt thereof, such as riboflavin, vitamin B5 or a derivative thereof or a salt thereof, such as pantothenic acid, calcium pantothenate, vitamin B6 or a derivative thereof or a salt thereof, such as pyridoxine, pyridoxine hydrochloride, pyridoxal or pyridoxamine, vitamin B 12 or derivatives thereof or salts thereof, such as cyanocobalamin, vitamin C or derivatives thereof or salts thereof, such as ascorbic acid, vitamin P (hesperidin) or derivatives thereof or salts thereof, can be exemplified. Examples of hypnotics and sedatives include allylisopropylacetylurea and bromvalerylurea. Examples of sputum dissolving agents include lysozyme chloride, L-ethylcysteine ​​hydrochloride, and methylcysteine ​​hydrochloride. Examples of anti-inflammatory agents include lysozyme chloride, serraptase, glycyrrhizic acid and its salts, and tranexamic acid and its salts. Examples of anticholinergic agents include belladonna total alkaloids and isopropamide iodide. Examples of Chinese herbal medicine prescriptions include Kakkonto, Kakkonto-ka-kikyo, Keipito, Kososan, Saiko-keipito, Sho-saikoto, Sho-seiryuto, Bakumondo-to, Hange-koboku-to, and Mao-to.

[0067] In addition to the above-mentioned components, the coated preparation or core of the present invention may further contain pharmaceutically acceptable carriers or additives conventionally used in the pharmaceutical technology field, as long as they do not impair the effects of the present invention. Examples of carriers or additives include excipients, disintegrants, binders, fluidizing agents, lubricants, colorants, pH adjusters, surfactants, stabilizers, flavoring agents, and fragrances. These carriers or additives are used in amounts conventionally used in the pharmaceutical technology field.

[0068] Examples of excipients include starches such as corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, and porous starch; sugars or sugar alcohols such as lactose hydrate, refined sucrose, fructose, glucose, mannitol, sorbitol, erythritol, xylitol, trehalose, maltitol, powdered reduced maltose syrup, and lactitol; anhydrous calcium hydrogen phosphate, crystalline cellulose, powdered cellulose, precipitated calcium carbonate, calcium carbonate, and calcium silicate. Examples of disintegrants that can be used include carmellose, carmellose calcium, sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose (L-HPC), and hydroxypropyl starch, and preferred are croscarmellose sodium and L-HPC. Examples of binders that can be used include hydroxypropyl cellulose, hydroxypropyl methylcellulose (hypromellose), polyvinylpyrrolidone, copolyvidone, powdered gum arabic, methylcellulose, low-substituted hydroxypropyl cellulose, carmellose sodium, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, and sodium alginate, with hydroxypropyl cellulose and hydroxypropyl methylcellulose being preferred. Examples of the fluidizing agent include light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, magnesium silicate, magnesium aluminometasilicate, and talc, with light anhydrous silicic acid and magnesium aluminometasilicate being preferred. Examples of lubricants include stearic acid, magnesium stearate, calcium stearate, talc, and sucrose fatty acid esters. Examples of coloring agents include yellow ferric oxide, ferric oxide, Food Blue No. 1, Food Blue No. 2, Food Yellow No. 4, Food Yellow No. 5, Food Green No. 3, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 104, Food Red No. 105, Food Red No. 106, food lake color, riboflavin, riboflavin sodium phosphate, and titanium oxide. Examples of pH adjusters include citric acid, phosphoric acid, carbonic acid, tartaric acid, fumaric acid, acetic acid, amino acids, and salts thereof. Examples of surfactants include sodium lauryl sulfate, polysorbate 80, polyoxyethylene (160) polyoxypropylene (30) glycol, and the like. Examples of stabilizers include tocopherol, tetrasodium edetate, nicotinamide, and cyclodextrins. Examples of flavoring agents include ascorbic acid, erythritol, citric acid, tartaric acid, malic acid, sucralose, and stevia extract. Examples of flavoring agents include L-menthol, mint oil, lemon oil, and vanillin.

[0069] As one embodiment, the present invention provides a method for producing a coated preparation in which a core is coated with two or more coating layers, comprising the steps of: a step of coating the core with a coating layer A containing a coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol in the coating layer A is 0.1:1 to 3:1; and a step of coating the core with a coating layer B containing a coating base containing methylcellulose; The present invention includes a manufacturing method including the steps of:

[0070] The coated formulation and core of the present invention are not particularly limited as long as they do not inhibit the effects of the present invention, and can be manufactured using general methods described in publications such as Granulation Handbook (edited by the Japan Powder Industry and Engineering Association, Ohmsha), Formulation Design of Orally Administered Formulations (edited by Hashida Mitsuru, Professor, Graduate School of Pharmaceutical Sciences, Kyoto University, Yakugyo Jihosha), Powder Compression Molding Technology (edited by the Powder Engineering, Formulation and Particle Design Committee, Nikkan Kogyo Shimbun), and Pharmaceutical Machinery Technology Handbook (2nd edition, edited by the Editorial Committee for the Publication Commemorating the 20th Anniversary of the Founding of the Pharmaceutical Machinery Technology Research Association, Pharmaceutical Machinery Technology Research Association).

[0071] For example, when the coated preparation of the present invention is formulated into tablets, the active ingredient and conventional pharmaceutically acceptable carriers or additives are mixed and granulated, and then compressed using various tableting machines commonly used in pharmaceutical formulations (e.g., rotary tableting machines, etc.) to obtain cores, i.e., plain tablets, which can then be coated with a coating layer to form coated tablets. Furthermore, when the solid preparation of the present invention is formulated into capsules, the active ingredient and conventional pharmaceutically acceptable carriers or additives are mixed and granulated, and the resulting cores are coated with a coating layer, and the granulated product can be filled into capsules to form capsules.

[0072] The coating method is not particularly limited, and the formulation can be coated with a coating layer using the general methods described in the above publications. For example, a coating liquid containing a coating base comprising a polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups on the cellulose skeleton and polyvinyl alcohol can be sprayed onto the core, dried by heating, and then a coating liquid containing a coating base comprising methylcellulose can be sprayed onto the core, and dried by heating to produce a coated formulation. Alternatively, a coating liquid containing a coating base comprising methylcellulose can be sprayed onto the core, dried by heating, and then a coating liquid containing a coating base comprising a polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups on the cellulose skeleton and polyvinyl alcohol can be sprayed onto the core, and then dried by heating to produce a coated formulation.

[0073] As described above, according to the present invention, it is possible to improve appearance defects such as cracks in the formulation due to expansion when the core is coated with two or more coating layers including the above-mentioned coating layer A and coating layer B. In contrast, when the core is coated with only either the above-mentioned coating layer A or coating layer B, no improvement in appearance defects such as cracks in the formulation due to expansion is observed.

[0074] According to one embodiment of the present invention, when coating layer A contains polyvinyl alcohol in combination with a polymeric polysaccharide having methoxy and / or hydroxypropoxy groups in the cellulose skeleton, it is possible to achieve improvement in appearance defects such as cracking of the formulation due to expansion. In contrast, when coating layer A does not contain polyvinyl alcohol, improvement in appearance defects such as cracking of the formulation due to expansion is not observed. Therefore, polyvinyl alcohol is an essential component of the coating layer A.

[0075] Furthermore, when the core containing vitamin B1 and nicotinic acids contains herbal medicines or their extracts, the occurrence of poor appearance such as cracks in the preparation due to expansion becomes significant. According to the present invention, even when the core contains herbal medicines or their extracts in addition to vitamin B1 and nicotinic acids, it is possible to achieve improvement in poor appearance such as cracks in the preparation due to expansion.

[0076] Furthermore, since expansion is suppressed not by the composition of the core, for example, the uncoated tablet, but by coating with the two or more coating layers, the components contained in the coated formulation and the amounts thereof are determined as desired depending on the function. Furthermore, the method for producing the coated formulation, for example, the core molding step and coating step, is not particularly limited, and conventional methods can be used as described herein. [Example]

[0077] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0078] According to Table 1, the tablets were granulated using a stirring granulator and a fluidized bed granulator, the granulated powder was dried and sized, and the resulting sized powder was mixed to form a mixed powder, which was then compressed using a rotary tablet press to obtain 235 mg core tablets. These core tablets were used in Examples 1 to 6 and Comparative Examples 1 to 6. [Table 1]

[0079] (Comparative Examples 1 to 3) The uncoated tablets obtained according to Table 1 were coated with Layer A using a coating machine at an inlet air temperature of approximately 70°C, with a coating solution prepared by dissolving the coating components according to Table 2 in purified water (production of coated tablets). [Table 2]

[0080] The resulting coated tablets were placed in a glass bottle, sealed, and stored at 60°C for one week, and the tablets were checked for cracks or breakage. The results are shown in Table 3. [Table 3]

[0081] The coating solution was prepared by dissolving the coating base in purified water according to Table 4 for the plain tablets in Table 1, and coating was carried out in the order of Layer A → Layer B using a coating machine at an inlet air temperature of approximately 70°C. [Table 4]

[0082] The obtained coated tablets were placed in a glass bottle, sealed, and stored at 60°C for 1 week, and the tablets were checked for cracks or breakage. The results are shown in Table 5. [Table 5]

[0083] In Examples 1 and 2 in which Layer B was added to Comparative Examples 1 and 3, no cracks or breaks were detected in the tablets, and the tablet appearance was good.

[0084] A coating solution was prepared by dissolving the coating base in purified water according to Table 6 for the plain tablets in Table 1, and coating was carried out in the order of Layer A → Layer B using a coating machine at an inlet air temperature of approximately 70°C, with Layer A not containing polyvinyl alcohol (Comparative Example 4). The obtained coated tablets were placed in a glass bottle and stored at 60°C with a tight seal for 1 week, after which the presence or absence of tablet cracks was checked. The results are shown in Table 7. [Table 6] [Table 7]

[0085] On the other hand, for the coating amount of Layer A containing polyvinyl alcohol, a coating solution was prepared by dissolving the coating base in purified water according to Table 6, and coating was performed using a coating machine at an inlet air temperature of approximately 70°C. The obtained coated tablets were placed in a glass bottle, sealed and stored at 60°C for one week, and the presence or absence of tablet cracks was confirmed (Examples 3 and 4). As a result, even when the coating amount was reduced from Examples 1 and 2, no cracks or breaks were detected in the tablets due to the formation of Layer B, and the tablet appearance was good.

[0086] Next, a coating solution was prepared by dissolving the coating base in purified water according to Table 8 for the plain tablets in Table 1, and the tablets were coated in the order of Layer B → Layer A using a coating machine at an inlet air temperature of approximately 70°C. The resulting coated tablets were placed in a glass bottle and stored at 60°C with a tight seal for 1 week, after which the presence or absence of tablet cracks was confirmed. The results are shown in Table 9. [Table 8] [Table 9]

[0087] Cracking and cracking of the tablets were observed only when Layer B was coated and Layer A was formed without containing polyvinyl alcohol (Comparative Example 5). Furthermore, even when the amounts of Layers A and B were significantly increased, cracking and cracking of the tablets were also observed when polyvinyl alcohol was not contained (Comparative Example 6). On the other hand, when Layer B was coated and Layer A containing polyvinyl alcohol was formed, no cracks or breaks were detected in the tablets, even though the amount of coating was small, and the tablet appearance was good (Examples 5 and 6).

[0088] According to Table 10, the tablets were granulated using a stirring granulator and a fluidized bed granulator, the granulated powder was dried, sized, and then mixed to form a mixed powder, which was then compressed using a rotary tablet press to obtain 245 mg core tablets. These core tablets were used in Examples 7 to 8 and Comparative Example 7. [Table 10]

[0089] The uncoated tablets obtained according to Table 10 were coated with a coating solution prepared by dissolving the coating components in purified water according to Table 11, and the tablets were coated using a coating machine at an inlet air temperature of about 70°C in the order of Layer A → Layer B for Comparative Example 7 and Example 7, and Layer B → Layer A for Example 8. The obtained coated tablets were placed in a glass bottle and stored at 60°C with a tight seal for up to 3 weeks, and the presence or absence of tablet cracks was confirmed. The results are shown in Table 12. [Table 11] [Table 12]

[0090] When only Layer A was coated, cracks and fractures were detected in the tablets (Comparative Example 7). On the other hand, when Layers A and B were coated, no cracks and fractures were detected in the tablets, and the tablet appearance was good (Examples 7 and 8).

[0091] As examples of solid preparations included in the present invention, Preparation Examples 1 to 5 are shown in Tables 13 and 14. The following Preparation Examples also have good tablet appearance after storage. [Table 13] [Table 14] [Industrial Applicability]

[0092] The coated preparation of the present invention can improve appearance defects such as cracks in the preparation due to expansion, thereby suppressing appearance defects such as cracks in the preparation and ensuring high quality of the preparation.

Claims

1. A coated formulation in which a core is coated with two or more coating layers, wherein the two or more coating layers are: (1) A coating layer A including a coating base containing a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group in a cellulose skeleton to the polyvinyl alcohol is 0.1:1 to 3:1; and (2) Coating layer B containing a coating base containing methylcellulose A coating formulation comprising:

2. 2. The coating formulation according to claim 1, wherein the amount of methylcellulose contained in coating layer B is 0.8% or more based on the mass of the core.

3. 2. The coated formulation according to claim 1, wherein the total amount of the coating base contained in coating layer A and coating layer B is 4% or more based on the mass of the core.

4. 2. The coating formulation according to claim 1, wherein the polymeric polysaccharide having methoxy groups and / or hydroxypropoxy groups on a cellulose skeleton is methylcellulose or hypromellose.

5. The nucleus is vitamin B 1 The coating formulation according to any one of claims 1 to 4, comprising a hydroxybenzoate and a nicotinic acid.

6. Vitamin B 1 The coating formulation according to claim 5, wherein the compound is selected from the group consisting of fursultiamine or a salt thereof and thiamine nitrate.

7. 6. The coating formulation according to claim 5, wherein the nicotinic acid derivative is nicotinamide.

8. The coated formulation according to claim 5, wherein the core further comprises a herbal medicine or an extract thereof.

9. 9. The coated formulation according to claim 8, wherein the herbal medicine or extract thereof comprises at least one selected from Astragalus Root, Shigoka, Ginseng, Eucommia Root, Peony Root, Poria Coccinea, Dioscorea Root, Cinnamon Bark, Lycium Bark, Luo Hua, Fennel, Atractylodes Root, Lithospermum Parkii, Lithospermum Root, Tangerine Peel, Cistanche Salicylate, and Longan Fruit, and extracts thereof.

10. 9. The coated formulation according to claim 8, wherein the herbal medicine or an extract thereof comprises at least one selected from Astragalus Root, Shigoka, Ginseng, Eucommia Root, Peony Root, Poria Coccus, Dioscorea Root, Cinnamon Bark, Lycium Bark, and Atractylodes Rhizome, and extracts thereof.

11. A method for producing a coated preparation in which a core is coated with two or more coating layers, comprising the steps of: a step of coating the core with a coating layer A containing a coating base comprising a polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group on a cellulose skeleton and polyvinyl alcohol, wherein the ratio of the polymeric polysaccharide having a methoxy group and / or a hydroxypropoxy group on a cellulose skeleton to the polyvinyl alcohol in the coating layer A is 0.1:1 to 3:1; and a step of coating the core with a coating layer B containing a coating base containing methylcellulose; A manufacturing method comprising:

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