Solid preparation, method for suppressing unpleasant odor of solid preparation, and composition for suppressing unpleasant odor

Abstract

The present invention addresses the problem of easily providing a solid preparation which contains an Agrimonia pilosa extract and a cellulose and in which an unpleasant odor thereof is suppressed.　In order to solve the above problem, provided is a solid preparation characterized by comprising components (A) to (C). Thus, it is possible to easily provide a solid preparation which contains an Agrimonia pilosa extract and a cellulose and in which an unpleasant odor is suppressed. (A) is an Agrimonia pilosa extract. (B) is a cellulose. (C) is a hydroxyalkyl cellulose or a hydroxyalkyl alkyl cellulose.

Description

Solid preparation, method for suppressing unpleasant odor of solid preparation, and composition for suppressing unpleasant odor.

[0001] The present invention relates to a solid preparation, a method for suppressing unpleasant odors in a solid preparation, and a composition for suppressing unpleasant odors. More specifically, the present invention relates to a solid preparation containing an agrimony extract and cellulose and having a suppressed unpleasant odor, which are used in the fields of pharmaceuticals, health foods, etc., and a method for suppressing unpleasant odors in a solid preparation containing an agrimony extract and cellulose, and a composition for suppressing unpleasant odors in a solid preparation.

[0002] Some ingredients contained in foods, pharmaceuticals, and quasi-drugs emit unpleasant odors. The unpleasant odors emitted by these ingredients can significantly affect consumer preference. Agrimony extract has recently attracted attention as an ingredient in foods, pharmaceuticals, and quasi-drugs. Agrimony B, in particular, has been shown to activate SIRT1, a longevity gene known for preventing biological aging and extending lifespan. It has also been shown to have various pharmacological effects, such as whitening due to its inhibitory activity against melanin production, improving type I allergies, and inhibiting muscle atrophy. While agrimony extract has been studied for various applications, when applied to specific formulations such as foods, pharmaceuticals, or quasi-drugs, the unique odor of agrimony extract has led to problems such as a decline in market value due to its impact on consumer preference and poor compliance due to difficulty in taking it as a medicine.

[0003] Regarding methods for suppressing such unpleasant odors in foods, pharmaceuticals, quasi-drugs, etc., Patent Document 1, for example, discloses a nutritional supplement composition in which an animal extract contains silicate in order to suppress the unpleasant odor of the animal extract. Also, Patent Document 2 discloses a formulation technology in which nabumetone is added to a pharmaceutical composition containing peony and / or an extract thereof to suppress the unpleasant odor of peony and / or an extract thereof.

[0004] JP 2021-29154 A JP 2018-58833 A

[0005] In investigating the formulation of agrimony extract, the present inventors encountered the problem that the addition of cellulose, a widely used excipient, to agrimony extract further strengthened the unpleasant odor of the agrimony extract. Methods for suppressing such a strong unpleasant odor generally involve the design of alternative formulations, such as sugar-coated or coated tablets, or granules, which are coated and granulated. However, such an increase in manufacturing steps poses cost problems, such as the need for expansion of manufacturing facilities. Therefore, a simple, low-cost method for suppressing the strong unpleasant odor of a formulation containing agrimony extract and cellulose is desired. Therefore, an object of the present invention is to easily provide a solid formulation containing agrimony extract and cellulose, which suppresses the unpleasant odor.

[0006] As a result of intensive research into the above-mentioned problems, the present inventors have discovered that by adding hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose to a composition or solid preparation containing agrimony extract and cellulose, the unpleasant odor caused by the agrimony extract and cellulose can be suppressed easily and at low cost without going through a coating or granulation process, and have completed the present invention.

[0007] That is, the present invention provides the following [1] to [8]. [1] A solid formulation comprising the following components (A) to (C): (A) agrimony extract; (B) cellulose; and (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. Even if this solid formulation contains agrimony extract and cellulose, the solid formulation can suppress the unpleasant odor by further containing hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. [2] The solid formulation according to [1], characterized in that the content of component (B) is 40% by mass or more. According to this feature, by specifying a lower limit for the cellulose content, the object of the present invention is more pronounced, and a solid formulation can be obtained that more efficiently achieves the effects of the present invention. [3] The solid formulation according to [1] or [2], characterized in that component (C) contains hydroxypropyl cellulose or hydroxypropyl methylcellulose. According to this feature, by limiting the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose to at least two of hydroxypropyl cellulose (hereinafter referred to as HPC) and hydroxypropyl methylcellulose (hereinafter referred to as HPMC), a solid preparation that more efficiently exhibits the unpleasant odor suppressing effect of the present invention can be obtained. [4] The solid preparation according to any of [1] to [3], characterized in that the ratio (A / C) of the content of component (A) to the content of component (C) is 0.3 to 20. According to this feature, by limiting the ratio (A / C) of the content of agrimony extract, which is the main cause of unpleasant odor, to the content of hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose within a specific range, a solid preparation that can more reliably exhibit the unpleasant odor suppressing effect of the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose can be obtained. [5] The solid preparation according to any of [1] to [4], characterized in that it is a tablet or capsule preparation. According to this feature, by limiting the solid preparation to a dosage form in which cellulose, a component that enhances the unpleasant odor of agrimony extract, effectively functions, a solid preparation that is more suitable for the present invention can be obtained.[6] The solid preparation according to any one of [1] to [5], characterized in that it is a capsule preparation containing the component (C) in the capsule shell. According to this feature, in a capsule preparation containing an agrimony extract and cellulose, which emit a strong unpleasant odor, by including hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose in at least the capsule shell, it is possible to obtain a solid preparation that reliably exhibits the unpleasant odor suppression effect of the present invention. [7] A method for suppressing an unpleasant odor in a solid preparation containing the following components (A) and (B), characterized in that the solid preparation contains the following component (C): (A) agrimony extract (B) cellulose (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose According to this method for suppressing an unpleasant odor in a solid preparation, even if the solid preparation emits a strong unpleasant odor due to the inclusion of an agrimony extract and cellulose, the unpleasant odor of the solid preparation can be easily suppressed by further including hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. [8] A composition for suppressing unpleasant odors in solid preparations, which is used to suppress the unpleasant odors of solid preparations containing (A) an agrimony extract and (B) cellulose, and which contains (C) a hydroxyalkyl cellulose or a hydroxyalkyl alkyl cellulose. According to this composition for suppressing unpleasant odors in solid preparations, the unpleasant odors of solid preparations that contain an agrimony extract and cellulose and therefore emit a strong unpleasant odor can be suppressed by applying a composition containing (C) a hydroxyalkyl cellulose or a hydroxyalkyl alkyl cellulose to the solid preparation.

[0008] According to the present invention, it is possible to easily provide a solid preparation containing an agrimony extract and cellulose, which has a reduced unpleasant odor.

[0009] The solid preparation, the method for suppressing an unpleasant odor from a solid preparation, and the composition for suppressing an unpleasant odor from a solid preparation of the present invention will be described below. Note that the solid preparation, the method for suppressing an unpleasant odor from a solid preparation, and the composition for suppressing an unpleasant odor from a solid preparation described in the embodiments are merely exemplified to explain the present invention, and the present invention is not limited to these.

[0010] [Solid Preparation] The solid preparation of the present invention is characterized by containing component (A) agrimony extract, component (B) cellulose, and component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. The peculiar unpleasant odor caused by the agrimony extract and cellulose contained in the solid preparation of the present invention can be easily and inexpensively suppressed by further containing hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

[0011] <Composition> The composition of the present invention contains component (A) agrimony extract, component (B) cellulose, and component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose, and can be applied to the solid preparation of the present invention by formulation, etc. It is not necessary to contain all of components (A) to (C), and these components may be added during the process of formulation into a solid preparation. The form of the composition is not particularly limited, and may be a powder, granules, emulsion, suspension, liquid, or solid.

[0012] The components constituting the composition, solid preparation, and composition for suppressing unpleasant odors in a solid preparation of the present invention will be described in detail below. The content of each component refers to the content in the solid preparation unless otherwise specified.

[0013] <Agrimony Extract> The solid formulation of the present invention contains an agrimony extract as a plant extract. Agrimonia (scientific name: Agrimonia pilosa) is a perennial plant of the genus Agrimonia in the family Rosaceae, and grows wild on forest edges, in fields, and along roadsides in Honshu, Shikoku, Kyushu, and other areas. It is also known as dragon's tooth plant. In the present invention, the agrimony raw material can be obtained by collecting the whole plant, either wild or cultivated, and drying it naturally or by heat. Alternatively, dried agrimony commercially available as an ingredient in herbal medicines, folk remedies, and health foods (herbal teas) can also be used. Dried whole agrimony plants are commercially available under the herbal name Senkakuso.

[0014] The agrimony extract of the present invention may be an extract with water or various organic solvents, a distillate obtained by steam distillation, a dried powder, a grated product, or juice squeezed from a grated product, etc. From the viewpoint of the yield and purity of the agrimony extract, an extract with water or various organic solvents is preferred, and an extract with ethyl alcohol or a water-containing ethyl alcohol is more preferred.

[0015] Extraction with water or various organic solvents can be carried out by known extraction methods using water as well as various organic solvents and mixtures thereof as solvents. Prior to the extraction procedure, the raw material, or the material roughly chopped, may be washed with a hydrophobic or hydrophilic solvent alone or in a mixture of hydrophobic or hydrophilic solvents to remove unwanted substances such as pigments. Examples of hydrophobic solvents include chloroform, ether, hexane, cyclohexane, toluene, dichloromethane, petroleum ether, and benzene. Examples of hydrophilic solvents include lower alcohols (e.g., methyl, ethyl, n-propyl, isobutyl, or butyl alcohol), ethyl acetate, acetone, isopropyl alcohol, and acetonitrile. If desired, water may be added to the raw material to moisten it.

[0016] To perform extraction with water, for example, 0.5 to 10 parts by mass of water is added to 1 part by mass of the raw material, and extraction is carried out at 40 to 120°C for 5 minutes to 2 hours, preferably 10 to 60 minutes, and more preferably 10 to 20 minutes. The extraction efficiency can be increased by stirring. Extraction can also be carried out by heating under reflux. After extraction, filtration or squeezing is carried out using a filter cloth, filter, or wire mesh. In this case, pressure may be applied to increase the efficiency of the process. Alternatively, the extract can be obtained by centrifugation (1,000 to 20,000 rpm). To increase the recovery rate, this extraction and filtration process can be repeated 1 to 5 times.

[0017] To perform extraction with an organic solvent, for example, 0.5 to 10 parts by weight of the solvent is added to 1 part by weight of the raw material, and the extract can be obtained in the same manner as with water extraction. The aforementioned hydrophobic and hydrophilic solvents can be used alone or in combination, and aqueous solvents can also be used. In particular, when washing the raw material with a hydrophobic solvent to remove unwanted substances such as pigments before extraction as described above, and when washing the crude extract after extraction with a hydrophobic solvent as described below, the solvent used for extraction is preferably water, lower alcohol, or a 50 to 80% (v / v) aqueous lower alcohol. Examples of these lower alcohols include those listed above. Solvent removal can be performed using conventional methods such as filtration, centrifugation, and distillation. Active ingredients such as agrimol B contained in an agrimony extract may also be concentrated by various extraction procedures. The preferred content of agrimol B in an agrimony extract is not particularly limited, but is 0.0005 to 2% by weight based on the total solid formulation. The lower limit is more preferably 0.001% by mass or more, and even more preferably 0.005% by mass or more, and the upper limit is more preferably 0.5% by mass or less, and even more preferably 0.1% by mass or less.

[0018] A particularly preferred method for extracting an agrimony extract is, for example, the following specific example. Wild-growing or cultivated agrimony plants are harvested whole and then naturally or heat-dried. The shredded agrimony is then immersed in approximately 10 times the amount of water or 0 to 99.5% (v / v) ethyl alcohol, preferably 1 to 50% ethyl alcohol, and particularly preferably 5 to 10% ethyl alcohol, for 3 to 5 days at room temperature for extraction, or extracted at 50 to 80°C for 5 to 24 hours using a reflux condenser, followed by filtration to recover the extract. The water and ethyl alcohol are removed from the extract using a reduced-pressure vacuum dryer such as a rotary evaporator or a freeze-drying device to obtain an agrimony extract (solid).

[0019] A step of concentrating the agrimony extract may then be carried out. In this step, the agrimony extract is concentrated by washing with 0-40% ethyl alcohol to remove 0-40% ethyl alcohol-soluble components. Specifically, the agrimony extract (solid) is washed with 0-40% ethyl alcohol, particularly preferably 10-30% ethyl alcohol, and the 0-40% ethyl alcohol-soluble components, particularly preferably 10-30% ethyl alcohol, are removed by filtration or other means. The filtration residue is then subjected to a reduced-pressure vacuum drying apparatus such as a rotary evaporator or a freeze-drying apparatus to remove water and ethyl alcohol, thereby obtaining a more concentrated agrimony extract. The concentrated agrimony extract is then redissolved in 50-99.5% ethyl alcohol, particularly preferably 70-90% ethyl alcohol, and the excipients used in formulation are added and freeze-dried to obtain a concentrated agrimony extract of the desired concentration. Sieving may also be performed to facilitate mixing with other powders.

[0020] The content of component (A) agrimony extract in the solid formulation of the present invention is not particularly limited and can be varied depending on its purity, degree of purification, the subject and purpose of administration, etc., but is, for example, 0.5 to 70% by mass of the total solid formulation. The lower limit is more preferably 3% by mass or more, even more preferably 6% by mass or more, and most preferably 10% by mass or more. On the other hand, the upper limit is more preferably 50% by mass or less, even more preferably 35% by mass or less, and most preferably 28% by mass or less. By ensuring that the content is equal to or greater than the lower limit, the effect of the agrimony extract as an active ingredient can be reliably exerted, while at the same time, the problem of unpleasant odors caused by the agrimony extract and cellulose due to the inclusion of component (C), described below, can be more clearly addressed. On the other hand, by ensuring that the content is equal to or less than the upper limit, the unpleasant odor suppression effect can be more reliably exerted.

[0021] <Cellulose> The solid formulation of the present invention contains cellulose as component (B). Cellulose is a polymeric compound having a structure in which many β-glucose units are linearly polymerized via glycosidic bonds, and is widely used primarily as an excipient in the fields of food, pharmaceuticals, cosmetics, etc. Its effects include, for example, stabilizing the structure by improving texture through thickening and gelation, preventing separation of water and oil as an emulsifier, and ensuring appropriate shape and hardness as a binder. Furthermore, because it is tasteless, odorless, and has low allergenicity, it is used for a variety of purposes to improve product quality. However, adding cellulose, which is supposed to be tasteless and odorless, to agrimony extract can further enhance the distinctive unpleasant odor of the agrimony extract.

[0022] The cellulose that can be used in the present invention is not particularly limited as long as it is acceptable for use in pharmaceuticals, foods, veterinary drugs, feed, and the like, and examples thereof include fermented cellulose, powdered cellulose, and crystalline cellulose. Crystalline cellulose is obtained by partially depolymerizing α-cellulose obtained from fibrous plants with an acid and purifying it, and is available in powder and colloidal types. Of these, crystalline cellulose is more preferably used, and powder types are more preferably used, from the viewpoint of its high applicability to various dosage forms in formulations and its remarkable ability to solve the problems of the present invention. These celluloses may be used alone or in combination of two or more types.

[0023] The cellulose content in the solid preparation of the present invention is preferably 40% by mass or more based on the total mass of the solid preparation. The lower limit is more preferably 50% by mass or more, and even more preferably 60% by mass or more. The upper limit is not particularly limited, but is, for example, 90% by mass or less, more preferably 80% by mass or less. When the cellulose content satisfies the lower limit, performance such as fluidity, hardness, and uniformity of the preparation can be ensured, and a safe and stable preparation can be provided. Furthermore, the object of the present invention is more clearly ensured. On the other hand, when the upper limit is satisfied, the flexibility of formulation design, such as the content of the active ingredient and the impartation of functions, is ensured.

[0024] <Component (C) Hydroxyalkyl Cellulose or Hydroxyalkyl Alkyl Cellulose> The solid formulation of the present invention contains component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. Hydroxyalkyl cellulose is a cellulose ether having a structure in which the hydroxyl groups of cellulose are substituted with hydroxyalkoxyl groups. On the other hand, hydroxyalkyl alkyl cellulose is a cellulose ether having a structure in which the hydroxyl groups of cellulose are substituted with hydroxyalkoxyl groups and alkoxyl groups. The hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose that can be used in the solid formulation of the present invention is not particularly limited as long as it is acceptable for use in pharmaceuticals, foods, veterinary drugs, feed, etc., and salts thereof can also be used. The degree of substitution and the form of substitution are also not particularly limited. The alkyl contained in the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose may have a branched chain and have, for example, 1 to 5 carbon atoms, more preferably 1 to 3 carbon atoms. More specifically, the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose or salts thereof may be as follows:

[0025] Specific examples of hydroxyalkyl cellulose include hydroxypropyl cellulose (HPC), hydroxymethyl cellulose, hydroxyethyl cellulose, etc. On the other hand, specific examples of hydroxyalkyl alkyl cellulose include hydroxypropyl methyl cellulose (HPMC), hydroxyethyl methyl cellulose, hydroxyethyl ethyl cellulose, hydroxyethyl ethyl methyl cellulose, etc. The viscosity of the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is not particularly limited, but is, for example, 0.5 to 400 mPa·s.

[0026] Among these, from the viewpoint of the unpleasant odor suppression effect of the present invention, hydroxypropyl cellulose (HPC) or hydroxypropyl methyl cellulose (HPMC) is more preferably usable. Furthermore, the upper limit of the viscosity of these hydroxypropyl celluloses is not particularly limited, but is more preferably 400 mPa·s or less, and even more preferably 300 mPa·s or less. On the other hand, the lower limit of the viscosity of hydroxypropyl methyl cellulose is not particularly limited, but is more preferably 4 mPa·s or more. The upper limit is more preferably 150 mPa·s or less, even more preferably 100 mPa·s or less, and particularly preferably 60 mPa·s or less. These hydroxyalkyl celluloses or hydroxyalkyl alkyl celluloses may be blended alone or in combination of two or more. Furthermore, the method for producing the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose of the present invention is not particularly limited, and they can be produced using known methods. Commercially available products can also be used as component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

[0027] The content of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is not particularly limited, but is, for example, 0.2 to 35% by mass relative to the total solid formulation. The lower limit is more preferably 0.5% by mass or more, even more preferably 1% by mass or more, and most preferably 5% by mass or more. On the other hand, the upper limit is not particularly limited, but is preferably 30% by mass or less, more preferably 25% by mass or less. By setting the content of hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose within the above range, the unpleasant odor suppression effect of the present invention can be fully exerted while at the same time ensuring freedom in formulation design. Furthermore, it becomes possible to impart various effects as an additive to the solid formulation. Note that the above-mentioned preferred content is the same when component (C) is used as a capsule, and the following component ratios also apply.

[0028] <Component (A) / Component (C)> Furthermore, the ratio (A / C) of the amount of component (A) agrimony extract to the amount of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is not particularly limited, but is, for example, 0.3 to 20. The lower limit is more preferably 0.5 or more, even more preferably 0.75 or more. On the other hand, the upper limit is more preferably 11 or less, even more preferably 8 or less, and most preferably 4 or less. By ensuring that the amount of component (A) agrimony extract relative to the amount of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is equal to or greater than the lower limit, it is expected that the effects of the active ingredient will be ensured, as well as that fluidity and dispersibility will be improved, and the effects of the present invention will be efficiently exhibited. Furthermore, by ensuring that the ratio is equal to or less than the upper limit, the unpleasant odor suppression effect of the present invention can be fully exhibited, while ensuring flexibility in formulation design, and enabling added value such as improved moldability and stability, the inclusion of other ingredients, and the impartation of functionality.

[0029] <Component (B) / Component (C)> The mass ratio (B / C) of the content of component (B) cellulose to the content of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is not particularly limited and is, for example, 1 to 200. The lower limit is more preferably 1.5 or more, and even more preferably 1.7 or more. On the other hand, the upper limit is more preferably 100 or less, even more preferably 90 or less, particularly preferably 80 or less, and most preferably 9 or less. By setting the mass ratio (B / C) of the content of component (B) cellulose to the content of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose within the above range, it can be expected that the unpleasant odor suppressing effect of the present invention will be more efficiently exerted, appropriate fluidity and moldability will be imparted to solid preparations, and freedom in formulation design will be ensured.

[0030] <(Component (A) + Component (B)) / Component (C)> Furthermore, the mass ratio ((A+B) / C) of the sum of the contents of component (A) agrimony extract and component (B) cellulose to the content of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is not particularly limited and is, for example, 1 to 200. The lower limit is more preferably 2 or more, and even more preferably 2.5 or more. On the other hand, the upper limit is more preferably 100 or less, even more preferably 90 or less, and particularly preferably 10 or less. By setting the mass ratio of the sum of the contents of component (A) agrimony extract and component (B) cellulose to the content of component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose within the above range, it is expected that the unpleasant odor suppressing effect of the present invention can be more efficiently exhibited, sufficient efficacy of the active ingredient can be ensured, appropriate fluidity and moldability can be imparted to the solid preparation, and flexibility in formulation design can be ensured.

[0031] <Other Components> The solid preparation of the present invention may contain, as necessary, active ingredients and additives in addition to component (A) agrimony extract, component (B) cellulose, and component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. Specific examples of the additives include excipients, binders, disintegrants, lubricants, stabilizers, preservatives, colorants, flavorings, sweeteners, etc.

[0032] The active ingredient is not particularly limited as long as it exhibits efficacy and effect and is acceptable for use in pharmaceuticals, foods, veterinary drugs, feed, etc. Examples include medicinal ingredients and functional ingredients used in pharmaceuticals, quasi-drugs, OTC drugs, herbal medicines, natural medicines, cosmetics, beauty products, health foods, supplements, veterinary drugs, feed, etc. Specific examples of medicinal ingredients and functional ingredients include vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid, biotin, niacin, niacinamide, pantothenic acid, iron, copper, zinc, manganese, selenium, chromium, molybdenum, polyglutamic acid, wisteria tea polyphenols, lipid regulators, antidiabetic agents, antihypertensive agents, vasodilators, beta-adrenergic receptor blockers, cardiac ion channel agents, antiarrhythmic agents, anticoagulants, central nervous system function improvers, sympathomimetics, parasympathomimetics, antimuscarinic agonists, dopaminergic agents, tranquilizers, antidepressants, and anti-anxiety agents. Examples of such active ingredients include anti-aging agents, hypnotics, animal-derived substances, plant-derived substances, lapidin, nobiletin, sulforaphane, ampelopsin, curcumins, resveratrols, geraniol, osajin, isoliquiritigenin, hydroxytyrosol, 25-hydroxycholecalciferol, S-adenosylmethionine, anthocyanins, proteoglycans, N-acetylglucosamine, collagen, bilberry extract, carrot powder, malt extract, lotus germ extract powder, gokahi, licorice, peony, cinnamon bark, fennel, scutellaria, bifidobacteria, lactic acid bacteria, yeast, and dietary fibers such as polydextrose. Among these, it is preferable to use an active ingredient that exhibits a synergistic effect with the anti-aging effect expected as the effect of the essential ingredients of the present invention. Furthermore, these medicinal ingredients and functional ingredients may be formulated alone or in combination of two or more.

[0033] <Form of Solid Preparation> The form of the solid preparation of the present invention is not particularly limited as long as it is acceptable for use in pharmaceuticals, foods, quasi-drugs, veterinary drugs, feed, etc. Examples include powders or fine granules prepared as powders, as well as solid preparations such as plain tablets, sugar-coated tablets, buccal tablets, coated tablets, and chewable tablets, pills, soft capsules, hard capsules, and granules, and external preparations such as lozenges, ointments, creams, suppositories, and vaginal tablets. In view of the nature of the problem to be solved by the present invention, oral administration is more preferred.

[0034] Among these, from the viewpoint of realizing low cost, a powder form is more preferable, and a powder mixture in which powders of each component are mixed is even more preferable. Furthermore, when applied to capsules, component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose can be contained in the capsule shell. By containing component (C) in the capsule shell, it is possible to achieve the same unpleasant odor suppression effect as when mixed as a powder. Furthermore, component (C) may be dissolved in a solvent and sprayed onto a powder to form a granulated product. These formulations can be prepared by known means in the field of formulation.

[0035] Furthermore, depending on the purpose, these preparations can be used in processed foods, health foods (nutritional supplements, nutritionally functional foods, foods for the sick, foods for specified health uses, foods with functional claims, etc.), supplements, foods for the sick (hospital food, sick food, nursing care food, etc.), confectioneries, oils and fats, dairy products, retort foods, microwave foods, frozen foods, seasonings, health supplements, beverages, nutritional drinks, topical medicines, etc. Among these, use for oral administration as an anti-aging agent is preferred.

[0036] [Method for producing a solid preparation] The method for producing the solid preparation of the present invention is not particularly limited, and the solid preparation can be produced by a known method using known additives that are acceptable for use in foods, medicines, quasi-drugs, etc. For example, the production process for the composition may include, in addition to a step of stirring and mixing component (A), component (B), and component (C), steps of adding additives as needed, heating, drying, pulverizing, sieving, etc., and the order and conditions of these steps are not particularly limited. The solid preparation of the present invention can be obtained by using the obtained composition and appropriate additives and carrying out formulation steps such as a tableting step using a rotary tablet press or the like, a granulation step of various raw materials using a stirring and mixing granulation method or a fluidized bed granulation method, etc., and a capsule filling step.

[0037] Due to the above-mentioned features, the method for producing a solid preparation of the present invention makes it possible to easily produce a solid preparation in which the unpleasant odor caused by containing components (A) agrimony extract and (B) cellulose is suppressed by the action of the specific component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

[0038] [Method for suppressing unpleasant odor in solid preparations] The method for suppressing unpleasant odor in solid preparations of the present invention is a method for suppressing unpleasant odor in solid preparations containing component (A) agrimony extract and component (B) cellulose, characterized in that the solid preparation contains (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. Note that the agrimony extract, cellulose, hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose constituting the method for suppressing unpleasant odor in solid preparations may be the same as those in the solid preparations of the present invention.

[0039] Similarly, the amount of the agrimony extract, cellulose, hydroxyalkyl cellulose, or hydroxyalkyl alkyl cellulose added is not particularly limited, and may be, for example, any amount that satisfies the description of the agrimony extract, cellulose, hydroxyalkyl cellulose, or hydroxyalkyl alkyl cellulose in the solid formulation.

[0040] Due to the above-mentioned features, the method for suppressing unpleasant odors in solid preparations of the present invention can exert the effect of suppressing unpleasant odors in solid preparations containing agrimony extract and cellulose through the action of hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

[0041] [Composition for suppressing unpleasant odors in solid preparations] The composition for suppressing unpleasant odors in solid preparations of the present invention is used to suppress the unpleasant odors of solid preparations containing component (A) agrimony extract and component (B) cellulose, and is characterized by containing (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. Note that the agrimony extract, cellulose, hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose constituting the composition for suppressing unpleasant odors in solid preparations may be the same as those in the solid preparations of the present invention.

[0042] Similarly, the amount of the agrimony extract, cellulose, hydroxyalkyl cellulose, or hydroxyalkyl alkyl cellulose added is not particularly limited, and may be, for example, any amount that satisfies the description of the agrimony extract, cellulose, hydroxyalkyl cellulose, or hydroxyalkyl alkyl cellulose in the solid formulation.

[0043] Due to the above-mentioned characteristics, the composition for unpleasant odors in solid preparations of the present invention can exert the effect of suppressing the unpleasant odor of solid preparations containing agrimony extract and cellulose through the action of hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

[0044] Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples, and various modifications are possible within the technical concept of the present invention.

[0045] [Preliminary Test Example 1: Test to Confirm Unpleasant Odor in a Composition Containing an Agrimony Extract and Cellulose] A test to confirm the unpleasant odor of a composition containing an Agrimony extract and cellulose was carried out. More specifically, the effect of adding cellulose on enhancing the unpleasant odor was confirmed by the following sensory evaluation using Reference Examples 1 and 2, with a 100% Agrimony extract powder as a control.

[0046] <Preparation of Test Samples> Each sample was prepared by weighing each powder raw material according to the formulation shown in Table 2, mixing the raw materials in a mixer (S-3 see-through mixer, Tsutsui Scientific Instruments and Machinery Co., Ltd.), and sieving 5 g of the resulting composition through a 30-mesh sieve. Each bag was placed in an aluminum bag (Lamizip AL-F, manufactured by Seisan Nippon Sha), opened once, and then stored in a 40°C, 75% RH (relative humidity) environment for two weeks with the zipper closed (not completely sealed, allowing a small amount of water vapor to enter through the zipper). This resulted in the preparation of specimens for the compositions of Comparative Control 1, Comparative Example 1, Reference Examples 1, and Reference Examples 2. Unless otherwise specified, the numerical values ​​in each table represent the respective component compositions as % by mass of the total composition. Details of the raw materials used in this test example are shown in Table 1 below. The agrimony extract used in this example contained 0.095% by mass of Agrimole B and was obtained from Maruzen Pharmaceutical Co., Ltd.

[0047]

[0048] <Sensory Evaluation> After two weeks of storage, the compositions obtained as samples were evaluated for odor based on the following evaluation criteria. The evaluation was determined by consensus of three expert panelists.

[0049] (Evaluation Criteria) The evaluation criteria were as follows: agrimony extract alone was used as a control, and the level of odor was determined and evaluated by the panelists in accordance with the following criteria. Furthermore, ◯ and ⊚ were deemed to have a high effect of suppressing unpleasant odors and were considered to be pass (examples), and the respective results are shown in Table 2. ⊚: no odor detected; ◯: slight odor detected but not unpleasant; △: odor suppressed more than the control, but unpleasant odor still present; ×: unpleasant odor equivalent to the control; XX: unpleasant odor stronger than the control. The sensory evaluation was also carried out in the following sensory tests using the same method.

[0050]

[0051] (Results) Comparison of Comparative Example 1, Reference Examples 1 and 2 with the control containing 100% agrimony extract revealed that the addition of cellulose to agrimony extract further enhanced the unpleasant odor of the agrimony extract. On the other hand, the addition of other commonly used excipients, such as maltitol and starch, did not enhance the unpleasant odor. This revealed the unique problem that a mixed composition of agrimony extract and cellulose synergistically produces a strong unpleasant odor.

[0052] [Test Example 1: Unpleasant Odor Suppression Effect of a Composition Containing an Agrimony Extract and Cellulose] A test was conducted to evaluate the unpleasant odor suppression effect of a composition containing an Agrimony extract and cellulose. More specifically, the unpleasant odor suppression effect was evaluated when a cellulose derivative powder was further added to a composition containing an Agrimony extract and cellulose to form a mixture.

[0053] <Preparation of Test Samples> Each sample was prepared using the blending composition shown in Table 3 in the same manner as in Preliminary Test 1, and specimens were obtained as compositions of Comparative Examples 1 to 3, Examples 1 to 7, and Comparative Examples 4 to 6. Five grams of each specimen of the obtained composition was stored in an aluminum bag in the same manner as in Preliminary Test 1, and the odor after storage for two weeks was evaluated in comparison with that of 100% agrimony extract (Comparative Control 1).

[0054]

[0055] (Results) The results of Comparative Examples 1 to 3 and Examples 1 to 7 revealed that compositions containing a certain amount of agrimony extract and cellulose have the problem of unpleasant odor, and that the unpleasant odor can be suppressed by further adding hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. On the other hand, the results of Comparative Examples 4 to 6 showed that another cellulose derivative, CMC-Na (sodium carboxymethylcellulose), did not have the effect of suppressing unpleasant odor.

[0056] Test Example 2: Examination of manufacturability and unpleasant odor suppression effect of tablets Tablet production: After weighing each powder raw material in the formulation shown in Table 4, the raw materials were mixed in a mixer (transparent mixer S-3, Tsutsui Scientific Instruments & Machinery Co., Ltd.) and sieved through a 30 mesh screen. The resulting mixture was compressed using a single punch tablet press (NE-30E, Okada Seiko Co., Ltd.) to obtain tablets of Comparative Control 2, Comparative Example 7, Examples 8 and 9. The tableting conditions were a tablet diameter of 8 mm, a tablet weight of 270 mg / grain, and a tableting pressure of 1000 kgf.

[0057] <Sensory evaluation and investigation of tableting> For 10 tablets compressed, a sensory evaluation was carried out on unpleasant odor after storage in an aluminum bag for 2 weeks, as in the preliminary test. Tableting properties were also evaluated. The evaluation of tableting properties for the 10 tablets produced was rated as "no problem" if no tableting problems such as capping or sticking occurred. These evaluations are also shown in Table 4.

[0058]

[0059] (Results) From the results of Examples 8 and 9, the unpleasant odor suppressing effect of adding HPMC (hydroxyalkyl alkyl cellulose) was confirmed even in tablets containing agrimony extract and cellulose. On the other hand, in Comparative Example 7, which does not contain HPMC, despite the low content of agrimony extract, it had the same unpleasant odor as Comparative Example 2, and no effect was observed. Therefore, it was revealed that even when formulated into tablets, the unpleasant odor suppressing effect of hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose on agrimony extract and cellulose can be obtained similar to that of the above-mentioned composition. At the same time, it was also revealed that the product has satisfactory tableting properties.

[0060] Test Example 3: Examination of the unpleasant odor suppressing effect in capsule formulations Preparation of hard capsule formulations Powder raw materials were mixed according to the formulations shown in Table 5, sieved through a 30-mesh sieve, and then filled into hard capsules of capsule size 2, such as HPMC capsules (Vcaps (registered trademark) Plus (size 2 VP.NATURAL B / C) manufactured by Lonza) or pullulan capsules (Plantcaps (size 2 PT.NATURAL B / C) manufactured by Lonza) using a hard capsule filling machine (profile100, manufactured by Lonza) to obtain the hard capsule formulations of Comparative Control 3 and Examples 10 to 12.

[0061] <Study by sensory evaluation> Thirty hard capsule preparations obtained were stored in aluminum bags for two weeks in the same manner as in the preliminary test. Sensory evaluation of odor after storage was performed in the same manner as in the preliminary test. The mass of each capsule shell (HPMC or pullulan) was 24% by mass of the content.

[0062]

[0063] (Results) As shown in Table 5, a comparison of Examples 10 to 12 with Comparative Control 3 revealed that the inclusion of HPMC (hydroxyalkyl alkyl cellulose) in a capsule formulation containing agrimony extract and cellulose suppressed unpleasant odors. Furthermore, as shown in Example 10, it was confirmed that a similar effect was achieved when HPMC was contained only in the hard capsule shell. It was also shown that a significant unpleasant odor suppression effect was achieved when HPMC was contained in both the hard capsule shell and the powder component. Therefore, it was revealed that the unpleasant odor suppression effect of the present invention can be achieved when the present invention is applied to a hard capsule formulation, regardless of whether hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose is contained in the fill or the capsule shell.

[0064] As described above, it has been confirmed that by adding component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose to a composition or solid preparation containing agrimony extract and cellulose, the unpleasant odor can be suppressed and that the composition or solid preparation can be formulated into tablets and capsules.

[0065] The present invention makes it possible to easily prepare compositions and solid preparations that contain agrimony extract and cellulose, which can cause a synergistic unpleasant odor, while suppressing their characteristic unpleasant odor.Therefore, it is possible to provide a wide range of products, including pharmaceuticals, quasi-drugs, drinkable cosmetics, drinkable cosmetics, health foods (nutritional supplements, nutritionally functional foods, foods for the sick, foods for specified health uses, foods with functional claims, etc.), supplements, feed, etc., that utilize the advantageous effects of agrimony extract as an active ingredient.

Claims

1. A solid preparation comprising the following components (A) to (C): (A) an extract of agrimony, (B) cellulose, and (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

2. The solid preparation according to claim 1, wherein the content of component (B) is 40% by mass or more.

3. A solid formulation according to claim 1 or 2, characterized in that component (C) contains hydroxypropyl cellulose or hydroxypropyl methylcellulose.

4. A solid preparation according to claim 1 or 2, characterized in that the ratio (A / C) of the content of component (A) to the content of component (C) is 0.3 to 20.

5. A solid formulation according to claim 1 or 2, characterized in that it is a tablet or capsule formulation.

6. A solid preparation according to claim 1 or 2, characterized in that it is a capsule preparation containing said component (C) in the capsule shell.

7. A method for suppressing an unpleasant odor in a solid preparation containing the following components (A) and (B), characterized in that the solid preparation also contains the following component (C): (A) an extract of agrimony, (B) cellulose, and (C) a hydroxyalkyl cellulose or a hydroxyalkyl alkyl cellulose.

8. A composition for suppressing unpleasant odors in solid preparations, characterized in that it is used to suppress unpleasant odors in solid preparations containing (A) agrimony extract and (B) cellulose, and contains (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose.

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