Solid pharmaceutical composition and method for producing the same
By adding cellulose and/or its derivatives to Kyosei Hadeki Gan extract and lactose, the challenge of forming granules is overcome, enabling the production of moldable solid pharmaceutical compositions.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- KOBAYASHI PHARMA CO LTD
- Filing Date
- 2024-10-30
- Publication Date
- 2026-07-30
AI Technical Summary
Existing methods for producing solid pharmaceutical compositions with Kyosei Hadeki Gan extract face challenges in achieving moldability due to the inability to form granules when using lactose as an excipient, as the slugs revert back to a powder state during crushing.
Incorporating cellulose and/or its derivatives into the composition with Kyosei Hadeki Gan extract and lactose allows for the formation of granules through dry granulation, enhancing moldability.
The method enables the production of granules and tablets with excellent moldability, even when containing lactose, by using cellulose and/or its derivatives, facilitating dry granulation.
Smart Images
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Abstract
Description
Technical Field
[0001] The present invention relates to a solid pharmaceutical composition containing a voice-breaking flute pill extract and having excellent moldability, and a method for producing the same.
Background Art
[0002] It is known to apply traditional Chinese medicine prescriptions such as voice-breaking flute pills, expelling wind and detoxifying decoctions, lung-tonifying decoctions, and pinellia and magnolia bark decoctions to improve hoarseness and throat discomfort. Among these, the voice-breaking flute pill is a particularly widely used traditional Chinese medicine prescription.
[0003] As specific dosage forms of the voice-breaking flute pill, a liquid preparation is described in Patent Document 1, and a jelly preparation is described in Patent Document 2. Also, lozenges are described in Patent Documents 3 and 4. The lozenges described in Patent Documents 3 and 4 are molded by binding with maltose or shaping with granulated sugar.
[0004] On the other hand, since the extract powder obtained by drying a traditional Chinese medicine extract generally has high hygroscopicity, when producing a pharmaceutical composition containing the extract powder as a granulated product, it is desirable to use a granulation method that does not require the addition of water (dry granulation method). Also, such a production method is desirable because it has good stability with respect to extract powders that are unstable in water.
[0005] As a specific method for producing a dry granulated product containing a traditional Chinese medicine extract powder, there is a method of preparing slugs by compression molding a mixture obtained by adding additives such as excipients to the traditional Chinese medicine extract powder, and then granulating by crushing the slugs. Also, in this case, lactose is often used as the excipient.
Prior Art Documents
Patent Documents
[0006]
Patent Document 1
Patent Document 2
[0007] The inventors attempted dry granulation using Kyosei Hadeki Gan extract and encountered a problem: unlike other herbal extracts, they could not obtain granules even when lactose was used as an excipient. In other words, when dry granulation of Kyosei Hadeki Gan extract using lactose as an excipient, slugs could not be obtained, or even if they were obtained, they reverted back to a powder state during the crushing process, making it impossible to granulate them as granules.
[0008] The present invention aims to provide a solid pharmaceutical composition containing Kyosei Hadeki Ganryo extract, which has excellent moldability, and a method for producing the same. [Means for solving the problem]
[0009] As a result of diligent research, the inventors of the present invention have found that the above objective can be achieved by adding cellulose and / or its derivatives to a solid pharmaceutical composition containing Kyosei Hadeki Gan extract together with lactose. The present invention was completed by further research based on this finding.
[0010] In other words, the present invention provides inventions in the following embodiments. Item 1. A solid pharmaceutical composition comprising (A) Kyosei Hadeki Gan extract, (B) cellulose and / or its derivatives, and (C) lactose. Item 2. The solid pharmaceutical composition according to Item 1, comprising 3 to 40% by weight of component (B). Item 3. The solid pharmaceutical composition according to item 1 or 2, comprising 0.06 to 1 part by weight of component (B) per 1 part by weight of component (A). Item 4. A solid pharmaceutical composition according to any one of items 1 to 3, comprising 0.05 to 2 parts by weight of component (B) per 1 part by weight of component (C). Item 5. A solid pharmaceutical composition according to any one of items 1 to 4, which is in the form of granules or tablets. Item 6. Step 1 involves compressing and molding a pharmaceutical composition comprising (A) Kyosei Hadeki Gan extract, (B) cellulose and / or its derivatives, and (C) lactose to obtain a slug. A method for producing a solid pharmaceutical composition, comprising step 2 of crushing the slug to obtain granules. Item 7. A method for producing a solid pharmaceutical composition according to item 6, further comprising step 3 of compressing the granules into tablets. [Effects of the Invention]
[0011] The solid pharmaceutical composition of the present invention exhibits excellent moldability even while containing lactose along with Kyosei Hadeki Gan extract. Furthermore, the method for producing the solid pharmaceutical composition of the present invention makes it possible to perform granulation by dry granulation even while containing lactose along with Kyosei Hadeki Gan extract. [Modes for carrying out the invention]
[0012] 1. Solid pharmaceutical composition The solid pharmaceutical composition of the present invention is characterized by comprising (A) Kyosei Hadeki Gan extract (hereinafter sometimes referred to as component (A)), (B) cellulose and / or its derivatives (hereinafter sometimes referred to as component (B)), and (C) lactose (hereinafter sometimes referred to as component (C)). The solid pharmaceutical composition of the present invention will be described in detail below.
[0013] (A) Kyosei Hadeki Gan Extract The solid pharmaceutical composition of the present invention contains Kyosei Hadeki Gan extract as component (A). The crude drugs that make up Kyosei Hadeki Gan are forsythia, platycodon, licorice, cardamom, chuanxiong, oak, catechu, peppermint, and rhubarb. Alternatively, the crude drugs that make up Kyosei Hadeki Gan may be forsythia, platycodon, licorice, cardamom, chuanxiong, oak, catechu, and peppermint, without rhubarb. The Kyosei Hadeki Gan extract used in the present invention may be obtained from any of these Kyosei Hadeki Gan.
[0014] Furthermore, the quantities of each crude drug that make up Kyosei Hadeki Gan are as follows: Forsythia 2.5 parts by weight, Platycodon 2.5 parts by weight, Licorice 2.5 parts by weight, Amomum 1.0 part by weight, Ligusticum chuanxiong 1.0 part by weight, Oak 1.0 part by weight, Catechuan 2.0 parts by weight, Peppermint 4.0 parts by weight, and Rhubarb 1.0 part by weight.
[0015] The Kyosei Hadeki Gan extract used in the present invention can be obtained by extracting the aforementioned crude drug formulation by a known method. The method for extracting the crude drug formulation can be the same as the conventional method for extracting Kyosei Hadeki Gan extract. For example, the crude drug formulation can be extracted by adding about 10 to 30 times the amount of water and stirring at about 80 to 100°C for about 1 to 3 hours. After extraction, the solids can be removed by solid-liquid separation such as centrifugation or filtration, and if necessary, the Kyosei Hadeki Gan extract can be obtained by concentration treatment or drying treatment.
[0016] To obtain Kyosei Hadeki Gan extract as an extract powder, the extract, from which the solid components have been removed, can be concentrated as needed, and then subjected to drying treatments such as spray drying, vacuum concentration drying, or freeze-drying. Furthermore, excipients may be added to the extract as needed during the drying treatment (especially spray drying). Adding excipients in this way makes it possible to shorten the drying time. The type and amount of excipients added are the same as those used in the production of general herbal extract powders.
[0017] In addition, to obtain the extract of Kikusei Hadokumaru ingredients as a soft extract, the extract from which the solid content has been removed may be concentrated by vacuum concentration or the like. Further, an appropriate adsorbent (for example, anhydrous silicic acid, starch, etc.) may be added to the soft extract to obtain an adsorbed powder.
[0018] The extract of Kikusei Hadokumaru ingredients 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 disintegrability, it is preferably 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 according to the efficacy to be exhibited, etc. For example, as the solid content, 30 to 80% by weight can be mentioned. Further, since the solid pharmaceutical composition of the present invention has excellent moldability, even when a relatively large amount of the component (A) is contained, the moldability can be effectively exhibited. From such a viewpoint, as the content of the component (A) in the solid pharmaceutical composition of the present invention, as the solid content, more preferably 40 to 80% by weight, still more preferably 45 to 80% by weight, even more preferably 50 to 80% by weight, and particularly preferably 55 to 75% by weight can be mentioned.
[0020] (B) Cellulose and / or derivatives thereof The solid pharmaceutical composition of the present invention contains cellulose and / or its derivative as the component (B). A pharmaceutical composition containing lactose together with the extract of Kikusei Hadokumaru ingredients inherently has poor moldability and cannot be granulated by dry granulation. However, the solid pharmaceutical composition of the present invention can have excellent moldability while containing lactose together with the extract of Kikusei Hadokumaru ingredients by blending cellulose and / or its derivative. Among cellulose and its derivatives, cellulose is preferable from the viewpoints of stability, versatility, and economy.
[0021] The cellulose used in the present invention is not particularly limited, as long as it is edible or pharmaceutically acceptable, but specifically, crystalline cellulose is preferred. Cellulose derivatives are polymers in which some of the hydrogen atoms of the hydroxyl groups of cellulose are replaced with substituents such as methyl groups, ethyl groups, propyl groups, hydroxypropyl groups, and carboxymethyl groups. The cellulose derivatives used in the present invention are not particularly limited, as long as they are edible or pharmaceutically acceptable, but specifically, examples include hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxymethylcellulose, hydroxymethylethyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethylcellulose, and salts thereof (specifically, alkali metal salts such as sodium salts and potassium salts). These cellulose derivatives may be used alone or in combination of two or more. Among the cellulose derivatives, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and salts thereof are preferred from the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, 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, but for example, 3 to 40 parts by weight is given. 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 for example, component (B) is 0.06 to 1 part by weight per 1 part by weight of component (A). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, component (B) is preferably 0.08 to 0.8 parts by weight, more preferably 0.1 to 0.5 parts by weight per 1 part by weight of component (A).
[0024] In the solid pharmaceutical composition of the present invention, the ratio of component (C) to component (B) is not particularly limited, but for example, component (B) is 0.05 to 2 parts by weight per 1 part by weight of component (C). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, component (B) is preferably 0.1 to 1 part by weight, more preferably 0.2 to 0.5 parts by weight per 1 part by weight of component (C).
[0025] (C) Lactose The solid pharmaceutical composition of the present invention contains lactose as component (C). Pharmaceutical compositions containing lactose together with Kyosei Hadeki Gan extract inherently have poor moldability and cannot be granulated by dry granulation. However, the solid pharmaceutical composition of the present invention, by incorporating component (B), can have excellent moldability even while containing lactose together with Kyosei Hadeki Gan extract.
[0026] Lactose is a useful ingredient as an excipient, flavoring agent, disintegrant, etc. Examples of lactose include lactose monohydrate and anhydrous lactose, with lactose monohydrate being preferred.
[0027] The content of component (C) in the solid pharmaceutical composition of the present invention is not particularly limited, but for example, 20 to 60 parts by weight, 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 for example, component (C) is 0.3 to 1.5 parts by weight per 1 part by weight of component (A). From the viewpoint of obtaining better moldability of the solid pharmaceutical composition of the present invention, component (C) 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 per 1 part by weight of component (A).
[0029] menthol The solid pharmaceutical composition of the present invention may further contain menthol in addition to the above-mentioned components. Menthol is a known cooling agent.
[0030] The menthol can be the d-isomer, l-isomer, or dl-isomer, but the l-isomer and dl-isomer are preferred, and the l-isomer is more preferred. Alternatively, an essential oil containing menthol may be used as the menthol.
[0031] When the solid pharmaceutical composition of the present invention contains menthol, the menthol content is not particularly limited and can be set appropriately according to the cooling sensation to be imparted, for example, 0.01 to 0.75% by weight.
[0032] Furthermore, in the solid pharmaceutical composition of the present invention, it is more preferable to include 0.1 to 0.75% by weight of menthol. When menthol is included in the same amount in a solid pharmaceutical composition that does not contain component (A), the cooling sensation is enhanced but the astringent sensation is not. However, by including component (A) in the solid pharmaceutical composition of the present invention, when the menthol content is 0.1% by weight or more, both the cooling sensation and the astringent sensation can be enhanced. Therefore, even if the solid pharmaceutical composition of the present invention is molded into granules or tablets, which have a relatively short residence time in the oral cavity, the effect of enhancing both the cooling sensation and the astringent sensation can be effectively obtained. In addition, by limiting the menthol content to 0.75% by weight or less, the bitterness of menthol itself does not interfere with the taste. From the viewpoint of further enhancing the cooling sensation and astringent sensation, the menthol content 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 menthol content is 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 cooling and astringent sensations and suppressing the bitterness of menthol itself, for example, 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 of menthol per 100 parts by weight of component (A).
[0034] Note that the menthol blending ratios shown here are calculated based on the amount of menthol when using essential oils containing menthol.
[0035] High-intensity sweetener The solid pharmaceutical composition of the present invention may further contain a high-intensity sweetener in addition to the above-mentioned components. Furthermore, if the solid pharmaceutical composition of the present invention contains a high-intensity sweetener, it is preferable to include it together with the menthol described above. This makes it possible to mitigate the bitterness caused by menthol. In particular, when the menthol described above is contained in an amount of 0.1 to 0.75% by weight, it is possible to mitigate only the bitterness without impairing the cooling and astringent sensations enhanced by the menthol.
[0036] High-intensity sweeteners 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 Marantaceae family), and the sweetening components contained therein. Specific examples of sweetening components in stevia extract include stevioside and rebaudioside A. Specific examples of sweetening components in monk fruit extract include mogroside V. Specific examples of sweetening components in Thaumatococcus daniellii extract include thaumatin. Examples of artificial high-intensity sweeteners include aspartame, acesulfame K, sucralose®, saccharin, and neotame, with sucralose® being preferred. These high-intensity sweeteners may be used individually or in combination of two or more.
[0037] When the solid pharmaceutical composition of the present invention contains a high-intensity sweetener, the amount of the high-intensity sweetener is not particularly limited and can be set appropriately according to the flavoring to be imparted, for example, 0.1 to 0.5% by weight. From the viewpoint of better alleviating the bitterness caused by menthol, the amount 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. However, from the viewpoint of better alleviating the bitterness caused by menthol, for example, the ratio of the high-intensity sweetener 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 per 1 part by weight of menthol.
[0039] Other ingredients The solid pharmaceutical composition of the present invention may further contain, in addition to the above-mentioned components (A), (B), and (C), as well as menthol and high-intensity sweeteners as needed, additives and bases depending on the formulation. The additives and bases are not particularly limited to those that are pharmaceutically acceptable, but examples include lubricants, plasticizers, excipients, binders, disintegrants, isotonic 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 inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, and the like. These additives and bases may be used individually or in combination of two or more. Furthermore, the content of these additives and bases is set appropriately according to the type of additives and bases used, up to the limit that allows the composition to be molded as 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, with light anhydrous silicic acid being preferred. These lubricants may be used individually or in combination of two or more. When the solid pharmaceutical composition of the present invention contains a lubricant, the lubricant content is, for example, 0.1 to 1% by weight, preferably 0.3 to 0.7% by weight.
[0041] Examples of plasticizers include propylene glycol, polyethylene glycol, polypropylene glycol, glycerin, sorbitol, glycerin triacetate, diethyl phthalate, triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, acetyl triethyl citrate, triethyl citrate, tributyl citrate, and acetyl tributyl citrate, with propylene glycol being preferred. These plasticizers may be used individually or in combination of two or more. When the solid pharmaceutical composition of the present invention contains a plasticizer, the plasticizer content is, for example, 0.15 to 0.4% by weight, more preferably 0.2 to 0.3% by weight.
[0042] Furthermore, the solid pharmaceutical composition of the present invention may optionally contain other nutritional components or pharmacological components other than component (A). Such nutritional components or pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but examples include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives and hypnotics, antihistamines, caffeines, cardiotonic and diuretic agents, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, etc. These nutritional components or pharmacological components may be used individually or in combination of two or more. The content of these components may be appropriately determined depending on the type of component used.
[0043] Formulation The solid pharmaceutical composition of the present invention is molded as granules or tablets. The shape of the granules is irregular, and the average particle size is 20 to 100 mesh (passing through a 20-mesh sieve but not through a 100-mesh sieve), preferably 20 to 50 mesh. The tablets are compressed products of the granules (granules for tableting), and their shape and size are not particularly limited. Examples of tablet shapes 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 tablets is 3 to 8 mm, preferably 4 to 7 mm. The weight per tablet is 200 to 80 Examples include 0 mg, preferably 300-600 mg.
[0044] 2. Method for producing solid pharmaceutical compositions The present invention provides a method for producing a solid pharmaceutical composition comprising: step 1, compressing and molding a pharmaceutical composition containing (A) Kyosei Hadeki Ganryo extract, (B) cellulose and / or its derivatives, and (C) lactose to obtain a slug; and step 2, crushing the slug to obtain granules. In the present invention, the moldability is improved by including component (B) together with components (A) and (C), making it possible to granulate by a dry granulation method.
[0045] In step 1, a pharmaceutical composition containing the above-mentioned components (A), (B), and (C), along with menthol and a high-intensity sweetener as needed, and other components as needed, is compressed and molded to obtain a slug. A slug machine may be used for compression molding, or a roller compactor may be used to supply the mixture between two rollers and mold it into a plate or corrugated sheet. The pressure during compression molding can be, for example, 5 to 30 MPa.
[0046] In step 2, the slug is crushed to produce granules. The granules are then sieved to select granules with a predetermined average particle size. For example, to select granules with an average particle size of 20 to 100 mesh, the granules that pass through a 20-mesh sieve are obtained, and then the granules that do not pass through a 100-mesh sieve are obtained.
[0047] The method for producing a solid pharmaceutical composition of the present invention may further include step 3, in which granules are compressed into tablets. In step 3, the above-mentioned granules are used as tablet granules, and the tablet granules are compressed into tablets. The compression pressure is, for example, 4 to 20 kN when producing tablets with a concentration of 200 to 800 mg / tablet.
[0048] Purpose The solid pharmaceutical composition of the present invention may be used in any application where the efficacy of Kyosei Hadeki Ganryo extract is expected. For example, it can be used 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 strained vocalization, and people who have a weak throat and tend to lose their voice easily.
[0049] Dosage / Usage The solid pharmaceutical composition of the present invention is administered orally. The dosage of the solid pharmaceutical composition of the present invention is appropriately determined according to the purpose of administration, the age, sex, constitution, and severity of symptoms of the recipient, but for example, a dose of 3 to 7 g, preferably 3.5 to 6 g, of the solid content of Kyosei Hadeki Ganryo extract per person per day may be taken 1 to 3 times a day, preferably 2 or 3 times. There are no particular restrictions on the timing of administration, and it may be taken before meals, after meals, or between meals. [Examples]
[0050] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
[0051] Manufacturing of Kyosei Hadeki Gan Extract A crude drug preparation containing 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 cardamom, 1.0 part by weight of chuanxiong, 1.0 part by weight of oak, 2.0 parts by weight of catechu, 4.0 parts by weight of peppermint, and 1.0 part by weight of rhubarb was mixed with 20 times the amount of water and extracted at approximately 100°C for 1 hour while stirring. The extract was then collected by centrifugation, concentrated under reduced pressure, and dried using a spray dryer to obtain Kyosei Hadeki Gan extract powder.
[0052] [Example Test] Manufacturing of solid pharmaceutical compositions A mixture of Kyosei Hadeki Gan extract powder, cellulose and / or its derivatives, and lactose monohydrate was prepared. The mixture was fed between two rollers using a roller compactor and compressed into a plate-like slug at 10 MPa. The slug was granulated by crushing it using a crushing device. The granules were sorted using a 14-mesh sieve and a 42-mesh sieve to select fractions with an average particle size of 355 to 1180 μm. For crystalline cellulose, Ceolus KG-802 from Asahi Kasei Chemicals was used; for hydroxypropyl cellulose, HPC-L from Nippon Soda was used; for hydroxypropyl methylcellulose, TC-5 from Shin-Etsu Chemical Co., Ltd. was used; and for lactose monohydrate, Phamatose 200M from DFE Pharma was used.
[0053] Solid pharmaceutical compositions with the compositions shown in Tables 1 and 2 were prepared. More specifically, the solid pharmaceutical compositions of the Examples were prepared by the method described above, the solid pharmaceutical compositions of the Comparative Examples were prepared in the same manner as the Examples, except that cellulose and / or its derivatives were not used, and the solid pharmaceutical compositions of the Reference Examples were prepared in the same manner as the Examples, except that the crude drug extract powders shown in Table 2 were used instead of the Kyoseihadekigan extract powder. The moldability of the obtained solid pharmaceutical compositions was evaluated based on the following criteria.
[0054] ×: Slug is not formed. △: Slugs are formed, but they are turned into powder by crushing. ○: Slugs are formed and can be granulated by crushing.
[0055] The results are shown in Tables 1 and 2. As is clear from Table 1, the solid pharmaceutical compositions containing lactose along with Kyosei Hadeki Gan extract (Comparative Examples 1-3) did not form slugs when compressed, or if they did form, they were pulverized, making it impossible to obtain granules. As is clear from Table 2, the solid pharmaceutical compositions containing lactose along with herbal extracts other than Kyosei Hadeki Gan extract (Reference Examples 1-1 to 1-3) were able to obtain granules, indicating no problems with moldability. In other words, the inability to obtain granules with lactose is a problem specific to solid pharmaceutical compositions containing Kyosei Hadeki Gan extract. In contrast, as is clear from Table 1, the solid pharmaceutical compositions containing cellulose and / or its derivatives in addition to Kyosei Hadeki Gan extract (Examples 1-6) were able to obtain granules and exhibited excellent moldability.
[0056] [Table 1]
[0057] [Table 2]
[0058] [Example of a sample exam] Manufacturing of pharmaceutical compositions Pharmaceutical compositions with the compositions listed in Tables 3 and 4 were prepared. Specifically, powdered pharmaceutical compositions were prepared by mixing the ingredients listed in the tables in the proportions listed in the tables. The degree of coolness, astringency, and bitterness of the prepared pharmaceutical compositions was evaluated based on the following criteria. Note that astringency refers to a sensation of tightness in the tissues of the oral cavity and throat, while bitterness refers to a bitter taste felt in the oral cavity, especially on the tongue. In this reference test example, different sensations of taking the medication were evaluated.
[0059] (Evaluation of cooling and astringent sensations) ++++: I feel it very strongly +++: I feel it strongly ++: Feel +: Feels very weak -: I don't feel it.
[0060] (Evaluation of bitterness) +++++: I feel it very strongly. ++++: I feel it strongly +++: Feeling ++: Feels weak +: Feels very weak -: I don't feel it.
[0061] The results are shown in Tables 3 and 4. As is clear from Table 3, compared to the case containing only Kyosei Hadeki Gan extract (Reference Comparative Example 1), when Kyosei Hadeki Gan 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. However, when Kyosei Hadeki Gan extract contained 0.1% by weight or more of l-menthol (Reference Examples 1-9), both the cooling sensation and the astringent sensation were enhanced, resulting in a good taste. Furthermore, when sucralose was included along with Kyosei Hadeki Gan extract and l-menthol (Reference Examples 6-9), the bitterness was reduced without impairing either the enhanced cooling sensation or the astringent sensation, resulting in an even better taste. On the other hand, as is clear from Table 4, when herbal medicines other than Kyosei Hadeki Gan extract were included (Reference Examples 2-2 to 2-6), even when l-menthol was included at a concentration of 0.1% by weight or more, the cooling sensation was enhanced, but the astringent sensation was not. In other words, the effect of enhancing not only the cooling 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 Kyosei Hadeki Gan extract.
[0062] [Table 3]
[0063] [Table 4]
[0064] Furthermore, in Examples 1-6 of the aforementioned test examples, when l-menthol was added in the ratios shown in Table 3, as in Reference Examples 1-9, in addition to good moldability, an improvement in the taste by enhancing the cooling and astringent sensation, similar to Reference Examples 1-9, was also obtained. In addition, in Examples 1-6 of the aforementioned test examples, when l-menthol and sucralose were added in the ratios shown in Table 3, as in Reference Examples 6-9, in addition to good moldability, an improvement in the taste by enhancing the cooling and astringent sensation and reducing bitterness, similar to Reference Examples 6-9, was also obtained.
Claims
1. A solid pharmaceutical composition comprising (A) Kyosei Hadeki Gan extract, (B) cellulose and / or a derivative thereof, (C) lactose and 0.1 to 0.75% by weight of menthol, wherein the composition of (A) is present in an amount of 40 to 80% by weight.
2. The solid pharmaceutical composition according to claim 1, comprising 0.15 to 2 parts by weight of menthol per 100 parts by weight of component (A).
3. The solid pharmaceutical composition according to claim 1 or 2, comprising 3 to 40% by weight of component (B).
4. A solid pharmaceutical composition according to any one of claims 1 to 3, comprising 0.06 to 1 part by weight of component (B) per 1 part by weight of component (A).
5. A solid pharmaceutical composition according to any one of claims 1 to 4, comprising 0.05 to 2 parts by weight of component (B) per 1 part by weight of component (C).
6. A solid pharmaceutical composition according to any one of claims 1 to 5, which is in the form of granules or tablets.
7. Step 1 involves compressing and molding a pharmaceutical composition containing (A) Kyosei Hadeki Gan extract, (B) cellulose and / or its derivatives, (C) lactose, and 0.1 to 0.75% by weight of menthol, wherein the pharmaceutical composition contains 40 to 80% by weight of component (A), to obtain a slug. A method for producing a solid pharmaceutical composition, comprising step 2 of crushing the slug to obtain granules.
8. A method for producing a solid pharmaceutical composition according to claim 7, further comprising step 3 of compressing the granules into tablets to obtain tablets.