Solid pharmaceutical composition and method for producing the same

Abstract

To provide solid pharmaceutical compositions comprising Kyoseihatekigan extract and having excellent moldability, and to provide methods for producing the same.SOLUTION: A solid pharmaceutical composition comprising (A) Kyoseihatekigan extract, (B) cellulose and / or a derivative thereof, and (C) lactose can be manufactured by a manufacturing method comprising a step 1 of subjecting a pharmaceutical composition comprising (A) Kyoseihatekigan extract, (B) cellulose and / or a derivative thereof, and (C) lactose to compression molding to obtain a slug, and a step 2 of crushing the slug to obtain granules, due to its excellent moldability.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a solid pharmaceutical composition containing a Kyoseihafuekigan extract and having excellent moldability, and a method for producing the same. [Background technology]

[0002] It is known that Chinese herbal medicines such as Kyoseihateki-gan, Kakufugedoku-to, Hohai-to, and Hange-kouboku-to can be used to improve hoarseness and throat discomfort. Among these, Kyoseihateki-gan is a particularly widely used Chinese herbal medicine.

[0003] As specific dosage forms of Kyoseihatekigan, Patent Document 1 describes a liquid formulation, and Patent Document 2 describes a jelly formulation. Furthermore, Patent Documents 3 and 4 describe troches. Troches such as those described in Patent Documents 3 and 4 are formed by binding with starch syrup or shaping with white sugar.

[0004] On the other hand, since dried extract powders of herbal extracts are generally highly hygroscopic, it is considered desirable to use a granulation method that does not require the addition of water (dry granulation method) when producing a pharmaceutical composition containing extract powder as a granule. In addition, such a production method is also considered desirable because it provides good stability for extract powders that are unstable in water.

[0005] A specific method for producing dry granulations containing Kampo extract powder includes compressing a mixture of Kampo extract powder and additives such as excipients to prepare slugs, and then crushing the slugs to form granules. In this case, lactose is often used as the excipient. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2002-193827 A [Patent Document 2] JP 2017-137246 A [Patent Document 3] Japanese Patent Application Publication No. 05-070359 [Patent Document 4] Japanese Patent Application Publication No. 10-007578 Summary of the Invention [Problem to be solved by the invention]

[0007] The present inventors attempted dry granulation using Kyoseihafuekigan extract, but were faced with the problem that, unlike other herbal extracts, granules could not be obtained even when lactose was used as an excipient. In other words, when dry granulating Kyoseihafuekigan extract using lactose as an excipient, slugs were not obtained, or even if they were obtained, they returned to a powder state in the process of crushing the slugs, so they could not be granulated into granules.

[0008] The present invention aims to provide a solid pharmaceutical composition containing a Kyoseihafuekigan extract, which has excellent moldability, and a method for producing the same. [Means for solving the problem]

[0009] As a result of intensive research, the present inventors have found that the above-mentioned object can be achieved by adding cellulose and / or its derivatives to a solid pharmaceutical composition containing Kyoseihafue-gan extract together with lactose. Based on this finding, the present invention has been completed through further research.

[0010] That is, the present invention provides the following aspects. Item 1. A solid pharmaceutical composition comprising (A) a Kyoseihatekigan extract, (B) cellulose and / or a derivative thereof, and (C) lactose. Item 2. The solid pharmaceutical composition according to Item 1, comprising 3 to 40% by weight of the component (B). Item 3. The solid pharmaceutical composition according to Item 1 or 2, comprising 0.06 to 1 part by weight of the component (B) per 1 part by weight of the component (A). Item 4. The solid pharmaceutical composition according to any one of Items 1 to 3, comprising 0.05 to 2 parts by weight of the component (B) per 1 part by weight of the component (C). Item 5. The solid pharmaceutical composition according to any one of Items 1 to 4, which is in the form of granules or tablets. Item 6. A step 1 of compressing and molding a pharmaceutical composition containing (A) a Kyoseihatekimaru extract, (B) cellulose and / or a derivative thereof, and (C) lactose to obtain a slug; and step 2 of crushing the slugs to obtain granules. Item 7. The method for producing the solid pharmaceutical composition according to Item 6, further comprising a step 3 of compressing the granules to obtain tablets. Effect of the Invention

[0011] The solid pharmaceutical composition of the present invention exhibits excellent moldability even though it contains lactose as well as the Kyoseihafuemaru extract. Also, the manufacturing method of the solid pharmaceutical composition of the present invention makes it possible to carry out granulation by dry granulation even though it contains lactose as well as the Kyoseihafuemaru extract. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] 1. Solid pharmaceutical compositions The solid pharmaceutical composition of the present invention is characterized by comprising (A) Kyoseihafuekiganryo extract (hereinafter, also referred to as component (A)), (B) cellulose and / or its derivative (hereinafter, also referred to as component (B)), and (C) lactose (hereinafter, also referred to as component (C)). The solid pharmaceutical composition of the present invention will be described in detail below.

[0013] (A) Kyouseihatekigan extract The solid pharmaceutical composition of the present invention contains a Kyoseihafuekigan extract as component (A). The herbal medicines constituting Kyoseihafuekigan are Forsythia sieboldii, Platycodon grandiflorum, Licorice Root, Acanthus Root, Cnidium Root, Oak, Acacia Root, Mentha Root, and Rhubarb. The herbal medicines constituting Kyoseihafuekigan may also be Forsythia sieboldii, Platycodon grandiflorum, Licorice Root, Acanthus Root, Cnidium Root, Oak, Acacia Root, and Mentha Root, but not Rhubarb. The Kyoseihafuekigan extract used in the present invention may be obtained from any of these Kyoseihafuekigan.

[0014] The amounts of each herb that makes up Kyoseihafuekigan are 2.5 parts by weight of Forsythia, 2.5 parts by weight of Platycodon, 2.5 parts by weight of Licorice, 1.0 part by weight of Acanthus, 1.0 part by weight of Cnidium, 1.0 part by weight of Kashiwa, 2.0 parts by weight of Acacia, 4.0 parts by weight of Mentha, and 1.0 part by weight of Rhubarb.

[0015] The Kyoseihafuekigan extract used in the present invention can be obtained by extracting the herbal preparation by a known method. The method for extracting the herbal preparation may be the same as the conventional method for extracting the Kyoseihafuekigan extract, for example, by adding about 10 to 30 times the amount of water to the herbal preparation and stirring at about 80 to 100°C for about 1 to 3 hours. After extraction, the solid content is removed by solid-liquid separation such as centrifugation and filtration, and if necessary, the Kyoseihafuekigan extract is obtained by subjecting the mixture to concentration or drying.

[0016] To obtain Kyoseihafuekigan extract as an extract powder, the extract liquid from which the solids have been removed may be concentrated as necessary, and then subjected to a drying process such as spray drying, vacuum concentration drying, or freeze drying. When subjected to a drying process (particularly drying by spray drying), an excipient may be added to the extract liquid as necessary. Adding an excipient in this manner makes it possible to shorten the drying time. The type and amount of excipient added are the same as when producing general herbal extract powders.

[0017] To obtain the Kyoseihafuegan extract as a soft extract, the extract from which the solids have been removed may be concentrated by vacuum concentration, etc. Alternatively, a suitable adsorbent (e.g., silicic anhydride, starch, etc.) may be added to the soft extract to obtain an adsorbed powder.

[0018] The Kyoseihafuekigan extract used in the present invention may be either an extract powder or a soft extract, but from the viewpoint of obtaining a solid pharmaceutical composition with excellent disintegratability, it is preferable that it is an extract powder.

[0019] The content of the component (A) in the solid pharmaceutical composition of the present invention is not particularly limited and may be appropriately set depending on the efficacy to be exerted, and may be, for example, 30 to 80% by weight in terms of solid content. In addition, since the solid pharmaceutical composition of the present invention has excellent moldability, even if the component (A) is contained in a relatively large amount, the moldability can be effectively exerted. From this viewpoint, the content of the component (A) in the solid pharmaceutical composition of the present invention is, in terms of solid content, more preferably 40 to 80% by weight, even more preferably 45 to 80% by weight, even more preferably 50 to 80% by weight, and particularly preferably 55 to 75% by weight.

[0020] (B) Cellulose and / or its derivatives The solid pharmaceutical composition of the present invention contains cellulose and / or a derivative thereof as component (B). Pharmaceutical compositions containing lactose together with the Kyoseihafuemaru extract inherently have poor moldability and cannot be granulated by dry granulation, but the solid pharmaceutical composition of the present invention, by incorporating cellulose and / or a derivative thereof, can have excellent moldability even while containing lactose together with the Kyoseihafuemaru extract. Among cellulose and its derivatives, cellulose is preferred from the standpoints of stability, versatility, and economy.

[0021] The cellulose used in the present invention is not particularly limited, provided that it is edible or pharmaceutical acceptable, but specifically, crystalline cellulose is preferred. The cellulose derivative is a polymer in which a part of the hydrogen atoms of the hydroxyl group of cellulose is substituted with a substituent such as a methyl group, an ethyl group, a propyl group, a hydroxypropyl group, or a carboxymethyl group. The cellulose derivative used in the present invention is not particularly limited, provided that it is edible or pharmaceutical acceptable, but specifically, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethyl cellulose, and salts thereof (specifically, alkali metal salts such as sodium salt and potassium salt), and the like. These cellulose derivatives may be used alone or in combination of two or more kinds. Among the cellulose derivatives, from the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and salts thereof are preferred, and hydroxypropyl cellulose and hydroxypropyl methylcellulose are more preferred.

[0022] The content of component (B) in the solid pharmaceutical composition of the present invention is not particularly limited, and may be, for example, 3 to 40 parts by weight. From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, the content of component (B) in the solid pharmaceutical composition of the present invention is preferably 5 to 30 parts by weight, more preferably 8 to 15 parts by weight.

[0023] In the solid pharmaceutical composition of the present invention, the ratio of component (A) to component (B) is not particularly limited, but may be, for example, 0.06 to 1 part by weight of component (B) per part by weight of component (A). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, the ratio of component (B) per part by weight of component (A) is preferably 0.08 to 0.8 parts by weight, more preferably 0.1 to 0.5 parts by weight.

[0024] In the solid pharmaceutical composition of the present invention, the ratio of component (C) to component (B) is not particularly limited, but may be, for example, 0.05 to 2 parts by weight of component (B) per 1 part by weight of component (C). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, the ratio of component (B) per 1 part by weight of component (C) is preferably 0.1 to 1 part by weight, more preferably 0.2 to 0.5 part by weight.

[0025] (C) Lactose The solid pharmaceutical composition of the present invention contains lactose as component (C). Pharmaceutical compositions containing lactose together with the Kyoseihafuekigan extract inherently have poor moldability and cannot be granulated by dry granulation, but the solid pharmaceutical composition of the present invention can have excellent moldability even though it contains lactose together with the Kyoseihafuekigan extract by blending component (B).

[0026] Lactose is a useful ingredient as an excipient, flavoring agent, disintegrant, etc. Examples of lactose include lactose hydrate and anhydrous lactose, and preferably lactose hydrate.

[0027] The content of component (C) in the solid pharmaceutical composition of the present invention is not particularly limited, but may be, for example, 20 to 60 parts by weight, and preferably 30 to 60 parts by weight.

[0028] In the solid pharmaceutical composition of the present invention, the ratio of component (A) to component (C) is not particularly limited, but may be, for example, 0.3 to 1.5 parts by weight of component (C) per part by weight of component (A). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, the ratio of component (C) per part by weight of component (A) is preferably 0.3 to 1.4 parts by weight, more preferably 0.4 to 1.4 parts by weight, and even more preferably 0.5 to 1.0 parts by weight.

[0029] menthol The solid pharmaceutical composition of the present invention may further contain menthol in addition to the above-mentioned components. Menthol is a component known as a cooling agent.

[0030] The menthol may be any of d-, l-, and dl-isomers, preferably l- and dl-isomers, more preferably l-isomers. In addition, essential oils containing menthol may be used as the menthol.

[0031] When the solid pharmaceutical composition of the present invention contains menthol, the content of menthol is not particularly limited and may be appropriately set depending on the cooling sensation to be imparted, and may be, for example, 0.01 to 0.75% by weight.

[0032] Furthermore, in the solid pharmaceutical composition of the present invention, it is more preferable that the content of menthol is 0.1 to 0.75% by weight. When the solid pharmaceutical composition does not contain the component (A), the cooling sensation is enhanced but the astringent sensation cannot be enhanced. However, when the solid pharmaceutical composition of the present invention contains the component (A), when the content of menthol is 0.1% by weight or more, not only the cooling sensation but also the astringent sensation can be enhanced. Therefore, even if the solid pharmaceutical composition of the present invention is molded into granules or tablets that have a relatively short residence time in the oral cavity, the effect of enhancing the cooling sensation and the astringent sensation can be effectively obtained. In addition, by setting the content of menthol to 0.75% by weight or less, the bitterness of menthol itself is prevented from interfering with the feeling of taking the drug. From the viewpoint of further enhancing the cooling sensation and the astringent sensation, the content of menthol is more preferably 0.2 to 0.75% by weight, and even more preferably 0.25 to 0.75% by weight. Furthermore, from the viewpoint of further suppressing the bitterness of menthol itself, the content of menthol is particularly preferably 0.25 to 0.5% by weight, and most preferably 0.25 to 0.3% by weight.

[0033] When the solid pharmaceutical composition of the present invention contains menthol, the ratio of component (A) to menthol is not particularly limited, but from the viewpoint of enhancing the refreshing sensation and astringent sensation and suppressing the bitterness of menthol itself, for example, the amount of menthol per 100 parts by weight of component (A) is 0.15 to 2 parts by weight, preferably 0.3 to 1.5 parts by weight, more preferably 0.35 to 1.5 parts by weight, even more preferably 0.35 to 0.7 parts by weight, and particularly preferably 0.35 to 0.5 parts by weight.

[0034] The blending ratio of menthol shown here is a value converted into the amount of menthol when an essential oil containing menthol is used as the menthol.

[0035] High-intensity sweeteners The solid pharmaceutical composition of the present invention may further contain a high-intensity sweetener in addition to the above-mentioned components. When the solid pharmaceutical composition of the present invention contains a high-intensity sweetener, it is preferable to contain it together with the above-mentioned menthol. This can alleviate the bitterness caused by menthol. In particular, when the above-mentioned menthol is contained in an amount of 0.1 to 0.75% by weight, only the bitterness can be alleviated without impairing the refreshing feeling and astringent feeling enhanced by menthol.

[0036] The high-intensity sweetener may be naturally derived or artificially synthesized. Examples of naturally derived high-intensity sweeteners include plant extracts such as stevia, Monk fruit, and Thaumatococcus daniellii, a plant of the family Ardisiaceae, and sweet components contained therein. Specific examples of sweet components contained in stevia extract include stevioside and rebaudioside A. Specific examples of sweet components contained in Monk fruit extract include mogroside V. Specific examples of sweet components contained in Thaumatococcus daniellii extract include thaumatin. In addition, examples of artificial high-intensity sweeteners include aspartame, acesulfame K, sucralose (registered trademark), saccharin, neotame, and the like, and preferably sucralose (registered trademark). These high-intensity sweeteners may be used alone or in combination of two or more.

[0037] When the solid pharmaceutical composition of the present invention contains a high-intensity sweetener, the content of the high-intensity sweetener is not particularly limited and may be appropriately set depending on the taste to be imparted, and may be, for example, 0.1 to 0.5% by weight. From the viewpoint of better alleviating the bitterness of menthol, the content of the high-intensity sweetener is preferably 0.15 to 0.4% by weight, more preferably 0.2 to 0.3% by weight.

[0038] When the solid pharmaceutical composition of the present invention contains a high-intensity sweetener, the ratio of menthol to the high-intensity sweetener is not particularly limited. From the viewpoint of better alleviating the bitterness of menthol, for example, the ratio of the high-intensity sweetener to 1 part by weight of menthol is 0.2 to 1 part by weight, preferably 0.4 to 0.9 parts by weight, more preferably 0.5 to 0.9 parts by weight, and even more preferably 0.6 to 0.8 parts by weight.

[0039] Other Ingredients The solid pharmaceutical composition of the present invention may further contain additives and bases according to the formulation form in addition to the above-mentioned (A), (B), and (C) components, as well as menthol and high-intensity sweeteners that are blended as necessary. The additives and bases are not particularly limited as long as they are pharma- ceutically acceptable, and examples thereof include lubricants, plasticizers, excipients, binders, disintegrants, isotonicity agents, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, corrigents, flavorings, fragrances, powders, thickeners, dyes, and chelating agents. These additives and bases may be used alone or in combination of two or more. The contents of these additives and bases are appropriately set depending on the types of additives and bases used, within the limits that allow molding into a solid pharmaceutical composition.

[0040] Examples of lubricants include light anhydrous silicic acid, magnesium stearate, calcium stearate, stearic acid, talc, colloidal silica, synthetic aluminum silicate, magnesium aluminometasilicate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate, and preferably light anhydrous silicic acid. These lubricants may be used alone or in combination of two or more. When the solid pharmaceutical composition of the present invention contains a lubricant, the content of the lubricant is, for example, 0.1 to 1% by weight, preferably 0.3 to 0.7% by weight.

[0041] Examples of the plasticizer include propylene glycol, polyethylene glycol, polypropylene glycol, glycerin, sorbitol, glycerin triacetate, diethyl phthalate, triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, acetyl triethyl titrate, triethyl titrate, tributyl titrate, acetyl tributyl titrate, etc., and preferably propylene glycol. These plasticizers may be used alone or in combination of two or more. When the solid pharmaceutical composition of the present invention contains a plasticizer, the content of the plasticizer is, for example, 0.15 to 0.4% by weight, more preferably 0.2 to 0.3% by weight.

[0042] In addition, the solid pharmaceutical composition of the present invention may further contain other nutritional components or pharmacological components other than the component (A) as necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedatives, hypnotics, antihistamines, caffeines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, and vitamins. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of components to be used.

[0043] Formulation The solid pharmaceutical composition of the present invention is molded into granules or tablets. The shape of the granules is irregular, and the average particle size is 20 to 100 mesh (passes through a 20 mesh sieve but not through a 100 mesh sieve), preferably 20 to 50 mesh. The tablets are molded products of the granules (granules for tableting), and the shape and size thereof are not particularly limited. Examples of the tablet shape include round, oval, triangular, and square. In the case of round tablets, the diameter is 6 to 12 mm, preferably 8 to 10 mm. The thickness of the tablet is 3 to 8 mm, preferably 4 to 7 mm. The weight per tablet is 200 to 80 0 mg, preferably 300 to 600 mg.

[0044] 2. Method for producing solid pharmaceutical composition The method for producing a solid pharmaceutical composition of the present invention is characterized by comprising: step 1, compressing and molding a pharmaceutical composition containing (A) Kyoseihafuekiganryo extract, (B) cellulose and / or a derivative thereof, and (C) lactose to obtain slugs; and step 2, crushing the slugs to obtain granules. In the present invention, the moldability is improved by including component (B) together with components (A) and (C), and therefore granulation by a dry granulation method is possible.

[0045] In step 1, a pharmaceutical composition containing the above-mentioned components (A), (B), and (C); menthol and a high-intensity sweetener which are blended as necessary; and other components which are blended as necessary is compressed to obtain slugs. A slug machine may be used for compression molding, or a roller compactor may be used to supply the mixture between two rollers to mold it into a plate or corrugated plate shape. The pressure during compression molding may be, for example, 5 to 30 MPa.

[0046] In step 2, the slugs are crushed to form granules. The granules are sieved to select granules of a predetermined average particle size. For example, when selecting granules of an average particle size of 20 to 100 mesh, the granules are sieved through a 20 mesh sieve to obtain the granules that have passed through, and then further sieved through a 100 mesh sieve to obtain the granules that have not passed through.

[0047] The method for producing the solid pharmaceutical composition of the present invention may further include step 3 of compressing the granules to obtain tablets. In step 3, the above-mentioned granules are used as granules for tableting, and the granules for tableting are compressed into tablets. The compression pressure may be, for example, 4 to 20 kN when producing tablets of 200 to 800 mg / tablet.

[0048] Purpose The solid pharmaceutical composition of the present invention may be used for any purpose for which the efficacy of Kyoseihafuekigan extract is expected, for example, for people who have overused their vocal cords for a long period of time, people who have developed hoarseness or loss of voice due to forced vocalization, and people who have a weak throat and tend to lose their hoarseness easily.

[0049] Dosage / Usage The solid pharmaceutical composition of the present invention is used by oral administration. The dosage of the solid pharmaceutical composition of the present invention is appropriately set according to the purpose of administration, the age, sex, constitution, and severity of symptoms of the recipient, and for example, the amount of 3-7 g, preferably 3.5-6 g, of the solid content of Kyoseihafuekigan extract per person per day may be taken 1-3 times, preferably 2 or 3 times per day. The timing of taking the composition is not particularly limited, and may be before, after, or between meals. EXAMPLES

[0050] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0051] Manufacturing of Kyouseihatekigan extract A 20-fold amount of water was added by weight to a herbal medicine mixture containing 2.5 parts by weight of Forsythia, 2.5 parts by weight of Platycodon, 2.5 parts by weight of Licorice, 1.0 parts by weight of Acanthus, 1.0 parts by weight of Cnidium, 1.0 parts by weight of Quercus, 2.0 parts by weight of Acacia, 4.0 parts by weight of Mentha, and 1.0 parts by weight of Rhubarb, and extraction was performed with stirring at about 100° C. for 1 hour. The extract was then collected by centrifugation, concentrated under reduced pressure, and dried using a spray dryer to obtain Kyoseihafueki-gan extract powder.

[0052] [Test example] Preparation of solid pharmaceutical compositions The Kyoseihafuekimaru extract powder, cellulose and / or its derivatives, and lactose hydrate were mixed. The mixture was fed between two rollers of a roller compactor and compressed into a plate-shaped slug at 10 MPa. The slug was crushed using a crushing device to form granules. The granules were sorted using a 14 mesh sieve and a 42 mesh sieve to select a fraction with an average particle size of 355 to 1180 μm. As the crystalline cellulose, Ceolas KG-802 manufactured by Asahi Kasei Chemicals was used, as the hydroxypropyl cellulose, HPC-L manufactured by Nippon Soda was used, as the hydroxypropyl methylcellulose, TC-5 manufactured by Shin-Etsu Chemical Co., Ltd. was used, and as the lactose hydrate, Phamatose 200M manufactured by DFE Pharma was used.

[0053] Solid pharmaceutical compositions were prepared with the compositions shown in Tables 1 and 2. More specifically, the solid pharmaceutical compositions of the Examples were produced by the method described above, the solid pharmaceutical compositions of the Comparative Examples were produced in the same manner as in the Examples except that cellulose and / or its derivatives were not used, and the solid pharmaceutical compositions of the Reference Examples were produced in the same manner as in the Examples except that the herbal extract powder shown in Table 2 was used instead of the Kyoseihafuekiganryo extract powder. The moldability of the obtained solid pharmaceutical compositions was evaluated based on the following criteria.

[0054] ×: No slug formed △: Slugs are formed, but are pulverized by grinding. ○: Slugs are formed and can be granulated by grinding

[0055] The results are shown in Tables 1 and 2. As is clear from Table 1, the solid pharmaceutical compositions containing lactose together with the Kyoseihafuemaru extract (Comparative Examples 1 to 3) did not form slugs when compressed, or even if they did form, they were pulverized by grinding, so that granulated products could not be obtained. As is clear from Table 2, the solid pharmaceutical compositions containing lactose together with the herbal extract other than the Kyoseihafuemaru extract (Reference Examples 1-1 to 1-3) were able to obtain granulated products, so there were no problems with moldability. In other words, it was shown that the problem of not being able to obtain granulated products with lactose is a problem specific to solid pharmaceutical compositions containing the Kyoseihafuemaru extract. In contrast, as is clear from Table 1, the solid pharmaceutical compositions containing cellulose and / or its derivatives in addition to the Kyoseihafuemaru extract and lactose (Examples 1 to 6) were able to obtain granulated products and had excellent moldability.

[0056] [Table 1]

[0057] [Table 2]

[0058] [Reference test example] Preparation of pharmaceutical compositions Pharmaceutical compositions having the compositions shown in Tables 3 and 4 were prepared. Specifically, the components shown in the tables were mixed in the mixing ratios shown in the tables to prepare powdered pharmaceutical compositions. The prepared pharmaceutical compositions were evaluated for their refreshing sensation, astringent sensation, and bitterness based on the following criteria. The astringent sensation refers to a sensation of squeezing the tissues in the oral cavity or throat, while the bitterness refers to a bitter taste felt in the oral cavity, especially on the tongue, and in this reference test example, the different sensations when taken were evaluated.

[0059] (Evaluation of cooling sensation and astringent sensation) ++++: Feels very strong +++: Feeling strong ++:Feel +: Feels very weak -: No feeling

[0060] (Bitterness rating) +++++: Feels very strong ++++: Feels strong +++:Feel ++: Feels weak +: Feels very weak -: No feeling

[0061] The results are shown in Tables 3 and 4. As is clear from Table 3, when the Kyoseihafuekimaru extract contained less than 0.1% by weight of l-menthol (Reference Comparative Example 2), neither the cooling sensation nor the astringent sensation was enhanced, compared to when only the Kyoseihafuekimaru extract was contained (Reference Comparative Example 1), but when the Kyoseihafuekimaru extract contained 0.1% by weight or more of l-menthol (Reference Examples 1 to 9), both the cooling sensation and the astringent sensation were enhanced, and a good intake sensation was obtained. Furthermore, when the Kyoseihafuekimaru extract and l-menthol were contained together with sucralose (Reference Examples 6 to 9), only the bitterness was reduced without impairing either the enhanced cooling sensation or the astringent sensation, and an even better intake sensation was obtained. On the other hand, as is clear from Table 4, when herbal medicines other than Kyoseihafueki-gan extract were included (Reference Examples 2-2 to 2-6), even when 0.1% by weight or more of l-menthol was included, the refreshing sensation was enhanced, but the astringent sensation was not enhanced. In other words, it was shown that the effect of enhancing not only the refreshing sensation but also the astringent sensation by including 0.1% by weight or more of l-menthol is an effect unique to pharmaceutical compositions containing Kyoseihafueki-gan extract.

[0062] [Table 3]

[0063] [Table 4]

[0064] In addition, in the above-mentioned Test Examples 1 to 6, when 1-menthol was further blended in the ratios shown in Table 3 as in Reference Examples 1 to 9, in addition to good moldability, an improved effect of improved intake comfort due to enhanced cooling sensation and astringent sensation could be obtained, similar to Reference Examples 1 to 9. In addition, in the above-mentioned Test Examples 1 to 6, when 1-menthol and sucralose were further blended in the ratios shown in Table 3 as in Reference Examples 6 to 9, in addition to good moldability, a further improved effect of improved intake comfort due to enhanced cooling sensation and astringent sensation and reduced bitterness could be obtained, similar to Reference Examples 6 to 9.

Claims

1. A solid pharmaceutical composition comprising (A) Kyoseihatuemaru extract, (B) cellulose and / or a derivative thereof, and (C) lactose, the composition containing 40 to 80% by weight of the (A) component.

2. The solid pharmaceutical composition according to claim 1, further comprising 0.1 to 0.75% by weight of menthol.

3. 3. The solid pharmaceutical composition according to claim 1, further comprising menthol, the composition comprising 0.15 to 2 parts by weight of said menthol per 100 parts by weight of said component (A).

4. The solid pharmaceutical composition according to any one of claims 1 to 3, comprising 3 to 40% by weight of the component (B).

5. The solid pharmaceutical composition according to any one of claims 1 to 4, comprising 0.06 to 1 part by weight of said component (B) per 1 part by weight of said component (A).

6. The solid pharmaceutical composition according to any one of claims 1 to 5, comprising 0.05 to 2 parts by weight of said component (B) per 1 part by weight of said component (C).

7. The solid pharmaceutical composition according to any one of claims 1 to 6, which is in the form of granules or tablets.

8. A step 1 of compressing and molding a pharmaceutical composition containing (A) Kyoseihatuemaru extract, (B) cellulose and / or a derivative thereof, and (C) lactose, in an amount of 40 to 80% by weight of the component (A) to obtain a slug; and step 2 of crushing the slugs to obtain granules.

9. The method for producing a solid pharmaceutical composition according to claim 8, further comprising a step 3 of compressing the granules to obtain tablets.

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