Enteric-coated hard capsules, oral composition, and method for producing enteric-coated hard capsules

Abstract

The present invention provides an enteric-coated hard capsule, an oral composition, and a method for producing enteric-coated hard capsules, which disintegrate in the intestines without disintegrating in the stomach, while suppressing the impact on manufacturing characteristics. [Solution] The present invention provides an enteric-coated hard capsule comprising a body portion and a lid portion, wherein the boundary between the body portion and the lid portion is sealed with a material containing at least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, shellac, and sucrose fatty acid ester.

Description

Technical Field

[0001] The present invention relates to an enteric hard capsule configured to reach the intestine without disintegrating in the stomach and then disintegrate, an oral composition, and a method for producing an enteric hard capsule. Background Art

[0002] Conventionally, enteric capsules configured to encapsulate components or materials that are easily inactivated inside the stomach, reach the intestine without disintegrating in the stomach, and then disintegrate are known. Among enteric capsules, enteric hard capsules can be filled with a large amount of solid materials such as powder, and are therefore preferably used when ingesting food components such as lactic acid bacteria.

[0003] For example, the enteric hard capsule disclosed in Patent Document 1 has a surface of the hard capsule coated with an enteric coating layer containing shellac, and the surface thereof coated with an overcoat layer containing hydroxypropyl methylcellulose and hydroxypropyl cellulose. The enteric hard capsule disclosed in Patent Document 1 is composed of a main body portion and a cap portion, and a boundary between the main body portion and the cap portion is sealed. Prior Art Documents Patent Documents

[0004] Patent Document 1 Japanese Patent No. 6578459 Summary of the Invention Problems to be Solved by the Invention

[0005] However, conventional enteric-coated hard capsules, in which the boundary between the main body and the lid is sealed, sometimes disintegrated at the sealed area due to gastric juices during disintegration tests simulating the digestive process. On the other hand, if the thickness of the enteric coating layer is increased to suppress the disintegration of enteric-coated hard capsules in the stomach, problems arise such as a decrease in manufacturing characteristics due to increased manufacturing time and increased raw material costs.

[0006] This invention has been made in view of these circumstances, and its purpose is to provide an enteric-coated hard capsule, an oral composition, and a method for producing an enteric-coated hard capsule, configured to disintegrate in the intestines without disintegrating in the stomach, while suppressing the impact on manufacturing characteristics. [Means for solving the problem]

[0007] As a result of research conducted to solve the above-mentioned problems, the inventors have found that a predetermined enteric-coated hard capsule, an oral composition, and a method for producing enteric-coated hard capsules can solve the above-mentioned problems.

[0008] The following describes various methods for solving the above problems. The enteric-coated hard capsule of Embodiment 1 is an enteric-coated hard capsule comprising a body portion and a lid portion, wherein the boundary between the body portion and the lid portion is sealed with a material containing at least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, shellac, and sucrose fatty acid ester.

[0009] The enteric-coated hard capsule of embodiment 2 is an enteric-coated hard capsule comprising a body portion and a lid portion, wherein the boundary between the body portion and the lid portion is sealed with a material containing at least one polymer selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin.

[0010] Embodiment 3 is an enteric-coated hard capsule according to Embodiment 1 or 2, wherein the material further contains a sugar alcohol. Embodiment 4 is an enteric-coated hard capsule according to Embodiment 3, wherein the sugar alcohol is at least one selected from sorbitol, maltitol, reduced starch syrup, and erythritol.

[0011] Embodiment 5 is an enteric-coated hard capsule according to any one embodiment of Embodiments 1 to 4, wherein the enteric-coated hard capsule is coated on the surface of the hard capsule with a coating layer comprising at least one polymer selected from shellac, gellan gum, sodium alginate, and pectin.

[0012] The oral composition of embodiment 6 is characterized by comprising an enteric-coated hard capsule as described in any one embodiment of embodiments 1 to 5. The method for producing an enteric-coated hard capsule according to Embodiment 7 is a method for producing an enteric-coated hard capsule comprising a body portion and a lid portion, and the method includes the step of applying a solution containing at least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, shellac, and sucrose fatty acid ester to the boundary between the body portion and the lid portion and sealing it.

[0013] The method for producing an enteric-coated hard capsule according to embodiment 8 is a method for producing an enteric-coated hard capsule comprising a body portion and a lid portion, and the gist of this method is to apply a solution containing at least one polymer selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin, to the boundary between the body portion and the lid portion and seal it.

[0014] Embodiment 9 is a method for producing enteric-coated hard capsules according to Embodiment 7, wherein the content of shellac in the solution is less than 10% by mass. Aspect 10 is the method for producing an enteric hard capsule according to Aspect 7 or 8, wherein the solution further contains a sugar alcohol.

[0015] Aspect 11 is the method for producing an enteric hard capsule according to Aspect 10, wherein the sugar alcohol is at least one selected from the group consisting of sorbitol, maltitol, reduced starch syrup, and erythritol.

[0016] Aspect 12 is the method for producing an enteric hard capsule according to Aspect 7, wherein the solution further contains ethanol. [Effects of the Invention]

[0017] According to the enteric hard capsule, oral composition, and method for producing an enteric hard capsule of the present invention, the enteric hard capsule can be configured to reach the intestine without disintegrating in the stomach and then disintegrate in the intestine, while suppressing adverse effects on production characteristics. [Mode for Carrying Out the Invention]

[0018] <First Embodiment> A first embodiment embodying the enteric hard capsule according to the present invention will be described. The enteric hard capsule comprises a main body part and a cap part.

[0019] (Main Body Part and Cap Part) As materials for constituting the main body part and the cap part, known materials can be appropriately employed, and examples thereof include plant polysaccharides such as pullulan, cellulose derivatives such as hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC), and gelatin. Only one of these materials may be used, or two or more thereof may be used in combination. Among these, HPMC is preferably applied from the viewpoint of capsule strength.

[0020] (Seal Part) The boundary between the main body portion and the lid portion is sealed by forming a seal portion with a material containing at least one selected from the group consisting of HPMC, HPC, pullulan and gelatin, shellac, and sucrose fatty acid ester. This improves durability and suppresses disintegration of the seal portion by gastric juice. In addition, sealing can improve internal airtightness, and enhance effects such as storage stability and prevention of gastric juice intrusion after ingestion of the capsule.

[0021] Examples of fatty acids constituting the sucrose fatty acid ester include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, behenic acid, and erucic acid. The total content ratio of at least one selected from HPMC, HPC, pullulan and gelatin in the material constituting the seal portion, based on the total content of each component other than the solvent described below (hereinafter referred to as non-volatile content), is preferably 60% by mass or more and 90% by mass or less, more preferably 70% by mass or more and 85% by mass or less. Similarly, the content ratio of the polymer, based on the non-volatile content, is preferably 10% by mass or more and 25% by mass or less, more preferably 12% by mass or more and 20% by mass or less. Similarly, the content ratio of the sucrose fatty acid ester, based on the non-volatile content, is preferably 0.5% by mass or more and 5% by mass or less, more preferably 1% by mass or more and 4% by mass or less. By being defined within this range, disintegration in gastric juice can be further suppressed while maintaining enteric solubility.

[0022] It is preferable that the material further contains a sugar alcohol. Inclusion of the sugar alcohol can further improve durability in gastric juice. Specific examples of sugar alcohols include sorbitol, maltitol, reduced starch syrup, xylitol, and erythritol. The sugar alcohol is more preferably at least one selected from the group consisting of sorbitol, maltitol, reduced starch syrup, and erythritol from the viewpoint of particularly excellent durability in gastric juice.

[0023] In the material constituting the seal portion, the sugar alcohol content is preferably 0.5% to 5% by mass, and more preferably 1% to 4% by mass, in terms of non-volatile content. By defining it within this range, disintegration in gastric juice can be further suppressed while maintaining enteric coating.

[0024] (Coating layer) Enteric-coated hard capsules have an enteric coating layer covering the surface of the hard capsule. The coating layer can be made from any known material, such as a mixture of polymers, polyols, emulsifiers, basic amino acids, basic phosphates, etc. Examples of polymers include shellac, gellan gum, sodium alginate, pectin, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, and copolymers of methacrylate and ethyl acrylate. Among these, shellac is preferred from the viewpoint of obtaining excellent enteric coating properties. Examples of polyols include polyhydric alcohols such as glycerin and propylene glycol, and sugar alcohols such as sorbitol, maltitol, erythritol, and xylitol. Examples of emulsifiers include sucrose fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters, and polysorbates. These materials may be used individually or in combination of two or more. Examples of basic amino acids include arginine, lysine, ornithine, hydroxylysine, and histidine. These materials may be used individually or in combination of two or more. Examples of basic phosphates include trisodium phosphate, tripotassium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, tetrasodium pyrophosphate, and tetrapotassium pyrophosphate. These materials may be used individually or in combination of two or more. From the viewpoint of excellent durability in gastric juice and excellent disintegration in the intestines, it is preferable that the coating layer is made of at least one polymer selected from shellac, gellan gum, sodium alginate, and pectin.

[0025] The thickness of the coating layer can be set appropriately depending on the material to be applied, but preferably it is 1 mg / cm² per surface area of ​​the hard capsule. 2 More than 15mg / cm 2More preferably, 3 mg / cm³ 2 8 mg / cm³ or more 2 The coating is applied in the following quantities. This allows for the efficient production of a coating layer with excellent resistance to gastric juices, thereby minimizing the impact on manufacturing characteristics.

[0026] (Overcoat layer) The surface of the coating layer may be further covered with an overcoat layer. This overcoat layer configuration improves the impact resistance of the coating layer. The materials constituting the overcoat layer can be any known materials, such as mixtures of cellulose derivatives like HPMC and HPC, polyols, and emulsifiers. Specific examples of these materials are listed in the section on the coating layer.

[0027] The thickness of the overcoat layer can be set appropriately depending on the material being applied, but preferably it is 1 mg / cm² per surface area of ​​the hard capsule. 2 More than 5mg / cm 2 More preferably, 2 mg / cm³ 2 More than 4mg / cm 2 The following amounts are used for coating. This allows for the efficient production of an overcoat layer with excellent impact resistance, thus minimizing the impact on manufacturing characteristics. Furthermore, transparency can be maintained, improving appearance characteristics.

[0028] (others) The material enclosed in the enteric-coated hard capsule of this embodiment is not particularly limited and includes, for example, bacteria or components that make up bacteria that are used in food and beverages. Examples of bacteria include lactic acid bacteria, natto bacteria, and yeast.

[0029] <Method for manufacturing enteric-coated hard capsules> Next, a specific example of the method for producing enteric-coated hard capsules according to this embodiment will be described. First, the contents are filled into the main body. Then, the lid is placed over the main body, and a solution containing at least one selected from HPMC, HPC, pullulan, and gelatin, along with shellac and sucrose fatty acid ester, is applied to the boundary between the main body and the lid. Finally, the container is sealed by forming a seal portion of a predetermined thickness.

[0030] The solution can be applied by known methods, such as using a commercially available band sealing machine, applying it with a brush or similar tool, using a spatula, or applying it with a spray. The sealed portion can be formed, for example, by applying the solution to the boundary between the main body and the lid, and then drying it. The solution may be applied once or multiple times. When applying the solution multiple times, it is preferable to perform a drying process between applications.

[0031] The content of the above polymer in the solution is preferably less than 10% by mass. By defining it within this range, the handling of the solution can be improved. Furthermore, the total content of nonvolatile matter in the solution is not particularly limited, but from the viewpoint of imparting efficiency and improved handling, it is preferably 10% by mass or more and 50% by mass or less, more preferably 15% by mass or more and 40% by mass or less.

[0032] The solution preferably further contains a sugar alcohol. The sugar alcohol is more preferably at least one selected from sorbitol, maltitol, reduced starch syrup, and erythritol.

[0033] The solution uses, for example, water or ethanol as a solvent. It is preferable that the solvent include ethanol. Including ethanol in the solution improves the application efficiency and handling ease.

[0034] Subsequently, a coating layer is applied to the surface of the hard capsule. The coating layer can be formed by first preparing a coating solution by dissolving or dispersing the above-mentioned materials in a solvent such as water or ethanol, applying it to a predetermined thickness, and then drying it. The coating process can be carried out by employing known methods, such as a method in which hard capsules are placed in a drum and the coating solution is sprayed while the drum is rolled or rotated, or a method in which the coating solution is applied to hard capsules being transported on a conveyor. Known coating apparatuses that can be used include, for example, pan coating apparatuses, fluidized bed coating apparatuses, jet bed coating apparatuses, and rolling fluidized bed coating apparatuses.

[0035] If the enteric-coated hard capsule further has an overcoat layer, the overcoat layer is then applied to the surface of the coating layer. The overcoat layer can be formed by first preparing a coating solution by dissolving or dispersing the above-mentioned materials in a solvent such as water or ethanol, applying it to a predetermined thickness, and then drying it. The coating process can be carried out by employing known methods as appropriate. Known coating methods are the same as those listed in the section on coating layers.

[0036] <Operation and Effects of the First Embodiment> The operation and effects of the first embodiment will now be described. (1-1) The enteric-coated hard capsule comprises a body and a lid. The boundary between the body and the lid is sealed with a material containing at least one selected from HPMC, HPC, pullulan, and gelatin, as well as shellac and sucrose fatty acid ester. This configuration improves the durability of the seal. Furthermore, it is possible to provide an enteric-coated hard capsule that suppresses the collapse of the seal in gastric juice and has suitable enteric properties. In addition, since the collapse of the seal is suppressed in gastric juice in this case, it is not necessary to increase the thickness of the coating layer as in conventional enteric-coated hard capsules where the boundary between the body and the lid is sealed. In other words, the impact on manufacturing characteristics can be suppressed.

[0037] (1-2) If the material further contains sugar alcohols, its resistance to gastric juice can be further improved. (1-3) If the material further contains a sugar alcohol, and the sugar alcohol is at least one selected from sorbitol, maltitol, reduced starch syrup, and erythritol, its durability in gastric juice can be further improved.

[0038] (1-4) When the surface of a hard capsule is coated with a coating layer containing at least one polymer selected from shellac, gellan gum, sodium alginate, and pectin, it can be made more durable in gastric juice and more disintegrating in the intestines.

[0039] (1-5) A method for producing an enteric-coated hard capsule comprising a body and a lid includes the step of applying a solution containing at least one selected from HPMC, HPC, pullulan, and gelatin, shellac, and sucrose fatty acid ester to the boundary between the body and the lid and sealing it. According to this production method, enteric-coated hard capsules with suppressed influence on manufacturing characteristics can be efficiently obtained.

[0040] (1-6) When the shellac content in the solution is less than 10% by mass, the handling properties of the solution can be improved. (1-7) If the solution further contains ethanol, the handling of the solution can be improved.

[0041] <Second Embodiment> A second embodiment of the enteric-coated hard capsule according to the present invention will be described below. The following description will focus on the differences from the enteric-coated hard capsule of the first embodiment.

[0042] The enteric-coated hard capsule consists of a body and a lid. The body and lid are as described in the section on the first embodiment. (Seal part) The boundary between the main body and the lid is sealed by forming a seal portion with a material containing at least one polymer selected from HPMC, HPC, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin. This improves durability and suppresses the collapse of the seal portion by gastric juices. Furthermore, sealing improves the internal airtightness, enhancing storage stability and preventing gastric juices from entering after the capsule is ingested.

[0043] When sodium alginate is used as the polymer, a combination of pullulan or gelatin is preferred, and a combination of gelatin is more preferred. With such a combination, the durability of the seal can be further improved.

[0044] When gellan gum is used as the polymer, a combination of HPC, pullulan, or gelatin is preferred. Such combinations can further improve the durability of the seal. The above materials do not prevent further inclusion of sucrose fatty acid esters or sugar alcohols as described in the first embodiment.

[0045] (Coating layer and overcoat layer) Enteric-coated hard capsules have an enteric coating layer covering the surface of the hard capsule. The coating layer is the same as described in the first embodiment.

[0046] The surface of the coating layer may be further covered with an overcoat layer. The overcoat layer is the same as described in the first embodiment. (others) The material encapsulated in the enteric-coated hard capsule of this embodiment is not particularly limited and is the same as described in the first embodiment.

[0047] <Method for manufacturing enteric-coated hard capsules> Next, a specific example of the method for producing enteric-coated hard capsules according to this embodiment will be described. First, the contents are filled into the main body. Then, the lid is placed over the main body, and a solution containing at least one polymer selected from HPMC, HPC, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin is applied to the boundary between the main body and the lid. Finally, it is sealed by forming a seal portion of a predetermined thickness.

[0048] The method for applying the solution is the same as described in the first embodiment. The content of the above polymer in the solution is preferably less than 10% by mass. By defining it within this range, the handling of the solution can be improved. Furthermore, the total content of nonvolatile matter in the solution is not particularly limited, but from the viewpoint of imparting efficiency and improved handling, it is preferably 10% by mass or more and 50% by mass or less.

[0049] The solution may use water, ethanol, or other solvents. When pectin and HPMC or HPC are used together as materials, water is preferred as the solvent. Using water improves the durability of the seal. When other material combinations are used, it is preferable that the solvent include ethanol. The inclusion of ethanol in the solution improves the application efficiency and handling.

[0050] Subsequently, a coating layer is applied to the surface of the hard capsule. The method for applying the coating layer is the same as described in the first embodiment. If the enteric-coated hard capsule further has an overcoat layer, the overcoat layer is then applied to the surface of the coating layer. The method for applying the overcoat layer is the same as described in the first embodiment.

[0051] <Effects and Effects of the Embodiment> The operation and effects of this embodiment will now be described. In the second embodiment, in addition to the effects of the first embodiment, the following effects are provided.

[0052] (2-1) The enteric-coated hard capsule comprises a body and a lid. The boundary between the body and the lid is sealed with a material containing at least one polymer selected from HPMC, HPC, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin. This configuration improves the durability of the seal. Furthermore, it is possible to provide an enteric-coated hard capsule that suppresses the collapse of the seal in gastric juice and has suitable enteric coating properties. In addition, in this case, since the collapse of the seal is suppressed in gastric juice, it is not necessary to increase the thickness of the coating layer as in conventional enteric-coated hard capsules in which the boundary between the body and the lid is sealed. In other words, the impact on manufacturing characteristics can be suppressed.

[0053] (2-2) When the surface of a hard capsule is coated with a coating layer containing at least one polymer selected from shellac, gellan gum, sodium alginate, and pectin, it can be made more durable in gastric juice and more disintegrating in the intestines.

[0054] (2-3) A method for producing an enteric-coated hard capsule comprising a body and a lid includes the step of applying a solution containing at least one polymer selected from HPMC, HPC, pullulan, and gelatin, and at least one polymer selected from gellan gum, sodium alginate, and pectin, to the boundary between the body and the lid and sealing it. According to this production method, enteric-coated hard capsules with suppressed influence on manufacturing characteristics can be efficiently obtained.

[0055] <Example of changes> This embodiment can be implemented with the following modifications. This embodiment and the following modifications can be combined with each other to the extent that they do not contradict each other technically.

[0056] In the above embodiment, the sealing portion may be formed by the method described above after the coating layer and / or overcoat layer have been formed on the hard capsule surface. The materials constituting the sealing portion described above do not prevent the incorporation of other additives, such as emulsifiers, preservatives, stabilizers, and basic amino acids, within a range that does not impair the effects of the present invention. The amount of other additives is preferably 10% by mass or less, more preferably 5% by mass or less, in terms of nonvolatile content.

[0057] The enteric-coated hard capsules described above can be packaged in various forms, such as PTP packaging, bottle packaging, and pouches. • Other raw materials besides edible bacteria can be incorporated into the enteric-coated hard capsule, as long as they do not hinder the effects of the present invention. Other raw materials can be appropriately selected from known additives and functional materials depending on the purpose of administering edible bacteria. Examples of additives include excipients, lubricants, auxiliary agents, binders, bases, stabilizers, sugars, flavorings, sweeteners, oils and fats, food additives, bulking agents, emulsifiers, and surfactants. As excipients, known materials can be appropriately used, but examples include crystalline cellulose and starch. Examples of lubricants include stearate. Examples of auxiliary agents include silicon dioxide.

[0058] Examples of enteric-coated hard capsule contents include those containing lactic acid bacteria, edible starch, calcium stearate, silicon dioxide, etc. Furthermore, the amount of each component is not limited and can be appropriately determined according to the intended use.

[0059] The application form of enteric-coated hard capsules is not particularly limited and can be used, for example, in oral compositions such as health foods, nutritional supplements, and other supplements. [Examples]

[0060] The following are examples to illustrate the structure and effects of the present invention in more detail, but the present invention is not limited to these examples. <Test Example 1> (Disintegration test of the sheet in gastric juice) Sealing solutions for Examples 1-5 and Comparative Examples 1-7 were prepared. The types of components and their amounts contained in the sealing solutions for Examples 1-5 and Comparative Examples 1-7 are shown in Table 1. The values ​​in the "Amount (mass%)" column of Table 1 indicate the proportion of each component contained in the sealing solution. For Examples 1-5, the "Content in Non-Volatile Matter (mass%)" column of Table 1 shows the proportion of each component in the total material excluding water and ethanol used as solvents.

[0061] The sealing fluid contains HPMC (product name Metronos SE-03: manufactured by Shin-Etsu Chemical Co., Ltd.), HPC (product name CELNY SL: manufactured by Nippon Soda Co., Ltd.), pullulan (manufactured by Nagase Vita Co., Ltd.), gelatin (gelatin #250: manufactured by Nitta Gelatin Co., Ltd.), ethanol, water-soluble shellac preparation (product name AQshelax: manufactured by Freund Industrial Co., Ltd.), sorbitol, sucrose fatty acid ester (sucrose stearate: product name Sugar Ester S-570: manufactured by Mitsubishi Chemical Corporation), propylene glycol fatty acid ester (propylene glycol monostearate: product name Rikemar PS-100: manufactured by Riken Vitamin Co., Ltd.), sorbitan fatty acid ester (sorbitan stearate: product name Poem S-60V: manufactured by Riken Vitamin Co., Ltd.), lysolecithin (product name SLP-Paste Lyso: manufactured by Tsuji Oil Co., Ltd.), and glycerin fatty acid ester (glycerin monostearate: product name Poem V-100 (manufactured by Riken Vitamin Co., Ltd.) was used for each test. The water-soluble shellac preparation contained 10% by mass of shellac, 1.6% by mass of L-arginine, 5.0% by mass of ethanol, and 83.4% by mass of water. Ethanol was used as a solvent.

[0062] Next, the sealing liquids from Examples 1-5 and Comparative Examples 1-7 were used to form sheets with a thickness of 1 mm. These sheets were then cut into squares with sides of 2 cm. The results of the evaluation of the moldability of the sheets obtained in Examples 1-5 and Comparative Examples 1-7 are shown in the "Evaluation" column of Table 1. The evaluation was determined according to the following criteria.

[0063] • Evaluation criteria for "sheet moldability" ○ (Acceptable): A clean sheet was formed with a uniform thickness. × (Unacceptable): The resulting sheet was brittle, with small holes appearing in it.

[0064] Subsequently, for Examples 1-5 and Comparative Examples 1-7, the obtained sheets were immersed in 100 mL of the first disintegration test solution at room temperature for 10 minutes. The first disintegration test solution was a solution simulating gastric juice, and was prepared by dissolving 2.0 g of sodium chloride and 7.0 mL of hydrochloric acid in water to make a total volume of 1000 mL (pH 1.2).

[0065] The degree of dissolution of the sheets after treatment with the first disintegration test solution was visually inspected. The results are shown in the "Evaluation" column of Table 1. The evaluation was determined according to the evaluation criteria below.

[0066] • Evaluation criteria for "disintegration properties (first liquid)" 4: The sheet maintained its shape, and no dissolution was observed. 3: Dissolution was observed in a portion of the sheet, but the overall shape of the sheet was maintained.

[0067] 2: Dissolution was observed in a portion of the sheet, and the sheet was unable to maintain its shape. 1: The sheet has completely dissolved.

[0068] [Table 1]

[0069] (evaluation) As shown in Table 1, all of Examples 1 to 5 received a satisfactory evaluation regarding the moldability of the sheets.

[0070] The results from Example 1 showed that seals composed of materials containing HPMC, shellac, and sucrose fatty acid esters were found to have their disintegration in gastric juice suppressed. The results of Example 2 showed that, in addition to the material used in Example 1, seals made with a material containing sorbitol, a sugar alcohol, also suppressed disintegration in gastric juice.

[0071] The results from Examples 3-5 showed that seals composed of materials containing HPC, pullulan, or gelatin, shellac, and sucrose fatty acid esters were found to have their disintegration in gastric juice suppressed.

[0072] <Test Example 2> (Disintegration test of the sheet in gastric juice) Sealing solutions for Examples 6 to 15 were prepared. The types of components and their amounts contained in the sealing solutions for Examples 6 to 15 are shown in Table 2. The values ​​in the "Amount (mass%)" column of Table 2 indicate the proportion of each component contained in the sealing solution. In addition, the "Content in Non-Volatile Matter (mass%)" column of Table 2 shows the proportion of each component in the total material excluding water and ethanol used as solvents.

[0073] Using the same method as in Test Example 1, sheets were obtained that were molded into squares with a thickness of 1 mm and sides of 2 cm. For each sheet, the moldability and disintegration properties (first liquid) were evaluated using the same method as in Test Example 1. The results are shown in the "Evaluation" column of Table 2.

[0074] [Table 2]

[0075] (evaluation) As shown in Table 2, all of Examples 6 to 15 received a satisfactory evaluation regarding the moldability of the sheets.

[0076] The results from Examples 6-9 showed that seals made of materials containing HPMC, HPC, pullulan, or gelatin and gellan gum were found to have their disintegration in gastric juice suppressed.

[0077] The results from Examples 10 and 11 showed that seals made of materials containing pullulan or gelatin and sodium alginate were found to have their disintegration in gastric juice suppressed. The results from Examples 12-15 showed that seals made of HPMC, HPC, pullulan, or materials containing gelatin and pectin were found to have their disintegration in gastric juice suppressed.

[0078] <Test Example 3> (Manufacturing of enteric-coated hard capsules) As hard capsules, we used No. 3 capsules (product name No. 3 Transparent VP Hard Capsule HPMC: manufactured by Lonza Co., Ltd.) (contents 0.28 mL, long diameter 1.6 cm x short diameter 0.6 cm), which consist of a body and a lid made of HPMC. Using a capsule filling machine JCF-40 (manufactured by Qualicaps Co., Ltd.), we filled the body of the hard capsule with a mixed powder mainly composed of cellulose at a rate of 230 mg / capsule, and then covered it with the lid.

[0079] Subsequently, a solution consisting of the components shown in Table 3 below was prepared for use as a band seal. The same components as those used in <Test Example 1> above were used. The values ​​in Table 3 indicate the proportion of each component, and the unit is mass%.

[0080] Then, using a HICAPSEAL 125 band sealing machine (manufactured by Cryocaps Co., Ltd.), the above solution was applied to the boundary between the main body and the lid, and a band seal was applied. At this time, the production speed of band-sealed hard capsules was set to 60,000 capsules / hour. Approximately 40,000 band-sealed hard capsules were manufactured as a result. It was confirmed that there was no distortion in the seal of these band-sealed hard capsules and that there was no impact on manufacturability.

[0081] Next, a solution containing 97.07% water-soluble shellac preparation, 1.93% sucrose fatty acid ester, and 1.00% sorbitol was prepared and used as the coating solution. The same components as those used in <Test Example 1> above were used.

[0082] Then, using a fully automatic ventilated inclined drum coating apparatus DRC-500 (manufactured by Powrec), the coating solution was sprayed onto the surface of band-sealed hard capsules so that the dry mass of the coating film was 5 mg / capsule, 10 mg / capsule, 15 mg / capsule, and 20 mg / capsule, respectively. After drying, enteric-coated hard capsules with an enteric coating layer were obtained.

[0083] [Table 3]

[0084] (Collapse test) The enteric-coated hard capsules with different coating amounts obtained as described above were subjected to the disintegration tests shown in (1) and (2) below. In each test, six enteric-coated hard capsules were used for each example with a different coating amount.

[0085] The disintegration test was conducted in accordance with the 15th edition of the Japanese Pharmacopoeia (Disintegration Test Method). The test was performed using a commercially available disintegration test machine (manufactured by Toyama Sangyo Co., Ltd.), adjusted to smoothly perform up-and-down motion under conditions of a liquid temperature of 37°C in the beaker, 30 reciprocations / minute, and an amplitude of 55 mm. The state of disintegration of the capsule surface was visually confirmed after the predetermined time had elapsed.

[0086] (1) The obtained enteric-coated hard capsules were subjected to a disintegration test in 900 mL of disintegration test solution 1 for 120 minutes. Disintegration test solution 1 was the same as that used in <Test Example 1> above. (2) The obtained enteric-coated hard capsules were subjected to a disintegration test in 900 mL of disintegration test solution 2 for 60 minutes. Disintegration test solution 2 was a solution simulating intestinal fluid, and was prepared by adding 118 mL of 0.2 mol / L sodium hydroxide solution and water to 250 mL of 0.2 mol / L potassium dihydrogen phosphate solution to make a total volume of 1000 mL (pH 6.8).

[0087] [Table 4]

[0088] (evaluation) As shown in Table 4, in the disintegration test (1) for each example of enteric-coated hard capsule, 0 out of 6 capsules disintegrated. Therefore, it was found that the disintegration of each example of enteric-coated hard capsule in gastric juice was suppressed.

[0089] In the disintegration test (2), all enteric-coated hard capsules in each case disintegrated. Therefore, it was found that the enteric-coated hard capsules in each case disintegrated in the intestinal fluid. From these results, it was found that the enteric-coated hard capsules in each case disintegrated in intestinal fluid without disintegrating in gastric fluid.

Claims

1. An enteric-coated hard capsule comprising a main body and a lid, The boundary between the main body and the lid is, At least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, Shellac and, Enteric-coated hard capsules sealed with a material containing sucrose fatty acid ester.

2. An enteric-coated hard capsule comprising a main body and a lid, The boundary between the main body and the lid is, At least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, Enteric-coated hard capsules sealed with a material containing at least one polymer selected from gellan gum, sodium alginate, and pectin.

3. The enteric-coated hard capsule according to claim 1 or 2, wherein the material further contains a sugar alcohol.

4. The enteric-coated hard capsule according to claim 3, wherein the sugar alcohol is at least one selected from sorbitol, maltitol, reduced starch syrup, and erythritol.

5. The enteric-coated hard capsule according to claim 1 or 2, wherein the surface of the hard capsule is coated with a coating layer comprising at least one polymer selected from shellac, gellan gum, sodium alginate, and pectin.

6. An oral composition comprising an enteric-coated hard capsule according to claim 1 or 2.

7. A method for manufacturing an enteric-coated hard capsule comprising a main body and a lid, At least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, Shellac and, A method for producing an enteric-coated hard capsule, comprising the step of applying a solution containing sucrose fatty acid ester to the boundary between the main body and the lid and sealing it.

8. A method for manufacturing an enteric-coated hard capsule comprising a main body and a lid, At least one selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, pullulan, and gelatin, A method for producing an enteric-coated hard capsule, comprising the steps of applying a solution containing at least one polymer selected from gellan gum, sodium alginate, and pectin to the boundary between the main body and the lid, and sealing it.

9. The method for producing an enteric-coated hard capsule according to claim 7, wherein the content of shellac in the solution is less than 10% by mass.

10. The method for producing enteric-coated hard capsules according to claim 7 or 8, wherein the solution further contains a sugar alcohol.

11. The method for producing enteric-coated hard capsules according to claim 10, wherein the sugar alcohol is at least one selected from sorbitol, maltitol, reduced starch syrup, and erythritol.

12. The method for producing enteric-coated hard capsules according to claim 7, wherein the solution further contains ethanol.

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