To provide a solid preparation, a method for suppressing an unpleasant odor of the solid preparation and a composition for suppressing the unpleasant odor.

Abstract

An object of the present invention is to easily provide a solid preparation containing a Japanese agrimonia extract and cellulose and having a suppressed unpleasant odor.SOLUTION: To solve the above problems, the present invention provides a solid preparation comprising the following components (A) to (C): This makes it possible to easily provide a solid preparation containing a Japanese agrimonia extract and a cellulose and having a reduced unpleasant odor. (A) Japanese agrimonia extract (B) cellulose (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose SELECTED DRAWING: None

Description

[Technical Field]

[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. [Background technology]

[0002] Some ingredients contained in foods, medicines, and quasi-drugs emit unpleasant odors, which can have a significant impact on consumer preference. Agrimony extract has been attracting attention in recent years as an ingredient in foods, pharmaceuticals, and quasi-drugs. In particular, Agrimony B, contained in Agrimony extract, has been shown to have various pharmacological effects, such as activating SIRT1, a longevity gene that prevents aging and extends lifespan, as well as whitening effects due to its inhibitory activity on melanin production, improving type I allergies, and inhibiting muscle atrophy. Research into various uses of agrimony extract is underway, but when it is applied to specific formulations such as foods, medicines, or quasi-drugs, the unique odor of agrimony extract has posed problems, such as a decline in market value due to its impact on consumer preference, and poor compliance due to the difficulty of 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 to suppress the unpleasant odor of the animal extract. Patent Document 2 also discloses a formulation technology in which nabumetone is added to a pharmaceutical composition containing peony and / or its extract to suppress the unpleasant odor of peony and / or its extract. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2021-29154 [Patent Document 2] Japanese Patent Application Laid-Open No. 2018-58833 Summary of the Invention [Problem to be solved by the invention]

[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. To suppress such a strong unpleasant odor, other formulation designs, such as sugar-coated or coated tablets or granules, are generally envisioned. However, such an increase in manufacturing steps poses cost problems, such as the need to expand 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 preparation which contains an agrimony extract and cellulose and has a reduced unpleasant odor. [Means for solving the problem]

[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 preparation comprising the following components (A) to (C): (A) Agrimony extract (B) Cellulose (C) Hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose According to this solid preparation, even if a strong unpleasant odor is generated due to the inclusion of agrimony extract and cellulose, the solid preparation can be made to suppress the unpleasant odor by further containing hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. [2] The solid formulation according to [1], wherein the content of the component (B) is 40% by mass or more. According to this feature, by specifying the lower limit of the cellulose content, the object of the present invention becomes more apparent, and a solid preparation that more efficiently exhibits the effects of the present invention can be obtained. [3] The solid formulation according to [1] or [2], wherein the component (C) contains hydroxypropyl cellulose or hydroxypropyl methylcellulose. According to this feature, by limiting the hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose to contain at least two of hydroxypropyl cellulose (hereinafter referred to as HPC) or hydroxypropyl methyl cellulose (hereinafter referred to as HPMC), a solid preparation can be obtained that more efficiently exhibits the unpleasant odor suppression effect of the present invention. [4] The solid preparation according to any one of [1] to [3], wherein 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 can be obtained that can more reliably exhibit the unpleasant odor suppression effect of the present invention due to hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. [5] The solid formulation according to any one of [1] to [4], which is a tablet or capsule formulation. 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, can function effectively, a solid preparation more suitable for the present invention can be made. [6] The solid preparation according to any one of [1] to [5], which is a capsule preparation containing the component (C) in a capsule shell. According to this feature, in a capsule formulation containing agrimony extract, which emits a strong unpleasant odor, and cellulose, by including hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose in at least the capsule shell, it is possible to obtain a solid formulation 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 component (A) and component (B), characterized in that the method contains the following component (C): (A) Agrimony extract (B) Cellulose (C) Hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose According to this method for suppressing unpleasant odors in solid preparations, even if a solid preparation contains an agrimony extract and cellulose, and thus emits a strong unpleasant odor, the unpleasant odor of the solid preparation can be easily suppressed by further containing hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. [8] A composition for suppressing unpleasant odors in solid preparations, which is used to suppress unpleasant odors in solid preparations containing (A) agrimony extract and (B) cellulose, and which contains (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. This composition for suppressing unpleasant odors in solid preparations contains agrimony extract and cellulose, and by applying a composition containing (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose to a solid preparation that emits a strong unpleasant odor, the unpleasant odor of the solid preparation can be suppressed. [Effects of the Invention]

[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. DETAILED DESCRIPTION OF THE INVENTION

[0009] The solid preparation, the method for suppressing unpleasant odors from solid preparations, and the composition for suppressing unpleasant odors from solid preparations of the present invention will be described below. The solid preparations, the method for suppressing unpleasant odors from solid preparations, and the composition for suppressing unpleasant odors from solid preparations described in the embodiments are merely examples for the purpose of explaining the present invention, and are not limited to these.

[0010] [Solid preparations] The solid preparation of the present invention is characterized by containing component (A) an extract of agrimony, 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. Note that 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 whole plant, whether wild or cultivated, can be collected and naturally or heat-dried and used as the agrimony raw material. 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 using known extraction methods, using water as the solvent, as well as various organic solvents and mixtures thereof. Prior to the extraction procedure, the raw material, or the material roughly chopped, may be washed with a hydrophobic or hydrophilic solvent, either alone or in a mixture, 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 extraction with water. The solvent used can be the hydrophobic or hydrophilic solvents described above, either alone or in combination. Water-containing 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, or when washing the crude extract after extraction with a hydrophobic solvent as described below, water, lower alcohols, and 50 to 80% (v / v) water-containing lower alcohols are preferred. Examples of these lower alcohols include those described above. Solvent removal can be performed using conventional methods such as filtration, centrifugation, and distillation. Active ingredients such as Agrimony B contained in the Agrimony extract may also be concentrated by various extraction procedures. The preferred content of Agrimony B in the Agrimony extract is not particularly limited, but is 0.0005 to 2% by weight based on the total solid preparation. 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] Particularly preferred extraction methods for agrimony extract include, for example, the following. Wild or cultivated agrimony plants are harvested whole and air-dried or heat-dried. The shredded agrimony is then immersed in approximately 10 times its volume of water or 0-99.5% (v / v) ethyl alcohol, preferably 1-50% ethyl alcohol, and particularly preferably 5-10% ethyl alcohol, for 3-5 days at room temperature for extraction. Alternatively, extraction is performed at 50-80°C for 5-24 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] Next, a step of concentrating the agrimony extract may be carried out, in which the agrimony extract is concentrated by washing with 0 to 40% ethyl alcohol to remove components soluble in 0 to 40% ethyl alcohol. Specifically, this agrimony extract (solid matter) is washed with 0-40% ethyl alcohol, particularly preferably 10-30% ethyl alcohol, and components soluble in 0-40% ethyl alcohol, 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 blending with other powders.

[0020] The content of component (A) agrimony extract in the solid preparation 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 preparation. 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 at least 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 at most the upper limit, the unpleasant odor suppression effect can be more reliably exerted.

[0021] <Cellulose> The solid formulation of the present invention contains component (B), cellulose. Cellulose is a polymeric compound having a structure in which many β-glucose units are polymerized in a linear chain via glycosidic bonds. It 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, etc., and examples include fermented cellulose, powdered cellulose, and crystalline cellulose. Crystalline cellulose is obtained by partially depolymerizing α-cellulose obtained from fibrous plants with acid and purifying it, and is available in powder and colloidal forms. Among these, crystalline cellulose is more preferably used, and powder forms 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. 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 methylcellulose (HPMC) is more preferably used. 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 methylcellulose 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 mass of the solid preparation. 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 suppressing effect of the present invention can be fully exerted, and at the same time, the freedom of formulation design can be ensured. Furthermore, it becomes possible to impart various effects as an additive to a solid formulation. Note that, when component (C) is used as a capsule, the above-mentioned preferred content is the same, and the following component ratios also apply.

[0028] <Ingredient (A) / Ingredient (C)> Furthermore, the ratio (A / C) of the content of component (A) agrimony extract to the content 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, and 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 setting the content of component (A) agrimony extract relative to component (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose at or above the lower limit, it is expected that the effects of the active ingredient will be ensured, as well as fluidity and dispersibility will be improved, and the effects of the present invention will be efficiently exhibited. On the other hand, by setting the content at or below the upper limit, the unpleasant odor suppression effect of the present invention can be fully exhibited, and freedom in formulation design can be ensured, making it possible to increase added value such as improved moldability and stability, the inclusion of other ingredients, and the impartation of functionality.

[0029] <Ingredient (B) / Ingredient (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 is expected that the unpleasant odor suppression effect of the present invention can be more efficiently exerted, appropriate fluidity and moldability can be imparted to solid preparations, and freedom of formulation design can 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 may be, 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 exerted, 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 ingredients> 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 of the active ingredient include medicinal ingredients and functional ingredients used in pharmaceuticals, quasi-drugs, over-the-counter 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 essential ingredient 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 dosage form> 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, chewable tablets, etc., 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 pharmaceutical means.

[0035] Furthermore, depending on the purpose, these preparations can be used in processed foods, health foods (nutritional supplements, functional nutritional 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] [Solid dosage form manufacturing method] The method for producing the solid preparation of the present invention is not particularly limited, and the preparation can be carried out 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 the step of stirring and mixing component (A), component (B), and component (C), steps such as adding additives as necessary, heating, drying, pulverizing, and sieving, 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 using various raw materials by a stirring and mixing granulation method or a fluidized bed granulation method, 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 odors from solid preparations] The method for suppressing an unpleasant odor in a solid preparation of the present invention is a method for suppressing an unpleasant odor in a solid preparation containing component (A) agrimony extract and component (B) cellulose, and is characterized in that it contains (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. The agrimony extract, cellulose, hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose constituting the method for suppressing an unpleasant odor of a solid preparation may be the same as those in the solid preparation 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 unpleasant odors in solid preparations containing component (A) agrimony extract and component (B) cellulose, and is characterized by containing (C) hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose. The agrimony extract, cellulose, hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose constituting the unpleasant odor suppressing composition in the solid preparation may be the same as those in the solid preparation 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. [Example]

[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 Agrimony Extract and Cellulose] A test was conducted to confirm the unpleasant odor of a composition containing an agrimony extract and cellulose. 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 ingredient in the formulation shown in Table 2, mixing them in a mixer (S-3 see-through mixer, Tsutsui Scientific Instruments Co., Ltd.), and sieving 5 g of the resulting composition through a 30-mesh sieve. Each bag was placed in an aluminum foil bag (Lamizip AL-F, manufactured by Seisan Nippon Sha). After opening the bag, the bag was resealed (not completely sealed, allowing a small amount of water vapor to enter through the resealed opening) and stored at 40°C and 75% RH (relative humidity) for two weeks. This gave samples for the compositions of Comparative Example 1, Comparative Example 1, Reference Examples 1, and Reference Examples 2. Unless otherwise specified, the values ​​in each table represent the respective component compositions as % by mass of the total composition. Details of the ingredients 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] [Table 1]

[0048] <Sensory evaluation> The odor of the sample compositions stored for two weeks was evaluated based on the following evaluation criteria, which were determined by consensus of three expert panelists.

[0049] (Evaluation criteria) The evaluation criteria were as follows: agrimony extract alone was used as a control for comparison, and the odor level was determined by consensus of the panelists according to the following criteria: ◯ and ⊚ were considered to have a high unpleasant odor suppression effect and were therefore considered to be acceptable (Examples), and the results are shown in Table 2. ◎ No smell 〇 A slight odor is detected, but it is not an unpleasant odor. △··· The odor is suppressed more than the control, but there is still an unpleasant odor. ×: Unpleasant odor similar to that of the control ××: Stronger unpleasant odor than the control In the following sensory tests, sensory evaluation was carried out in the same manner.

[0050] [Table 2]

[0051] (result) 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 The unpleasant odor suppression effect of a composition containing an agrimony extract and cellulose was tested. 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 the compositions of Comparative Examples 1 to 3, Examples 1 to 7, and Comparative Examples 4 to 6 were obtained as specimens. A 5 g sample 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 2 weeks was evaluated in comparison with that of 100% agrimony extract (Comparative Control 1).

[0054] [Table 3]

[0055] (result) 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 did not confirm the unpleasant odor suppressing effect of another cellulose derivative, CMC-Na (carboxymethyl cellulose sodium).

[0056] [Test Example 2: Examination of manufacturability and unpleasant odor suppression effect in tablets] <Tablet preparation> After weighing each powder raw material in the formulation shown in Table 4, the raw materials were mixed in a mixer (S-3 see-through mixer, Tsutsui Scientific Instruments and Machinery Co., Ltd.) and sieved through a 30 mesh. 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, and Examples 8 and 9. The tableting conditions were a tablet diameter of 8 mm, tablet weight of 270 mg / tablet, and tableting pressure of 1000 kgf.

[0057] <Sensory evaluation and tableting evaluation> The ten compressed tablets were stored in aluminum bags for two weeks, and then subjected to a sensory evaluation for unpleasant odor, as in the preliminary test. Tableting properties were also evaluated. The ten tablets produced were rated as "no problem" if no tableting problems such as capping or sticking occurred. These evaluations are also shown in Table 4.

[0058] [Table 4]

[0059] (result) From the results of Examples 8 and 9, it was confirmed that the addition of HPMC (hydroxyalkyl alkyl cellulose) had an unpleasant odor suppressing effect even in tablets containing agrimony extract and cellulose. On the other hand, in Comparative Example 7, which did not contain HPMC, despite the low content of agrimony extract, it had an unpleasant odor equivalent to that of Comparative Control 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 had satisfactory tableting properties.

[0060] [Test Example 3: Examination of the unpleasant odor suppression effect in capsule formulations] <Preparation of hard capsule formulation> The powdered raw materials were mixed according to the formulation shown in Table 5 and sieved through a 30 mesh screen. Using a hard capsule filling machine (Profill100, manufactured by Lonza), the mixture was 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), to obtain the hard capsule formulations of Comparative Control 3 and Examples 10 to 12.

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

[0062] [Table 5]

[0063] (result) As shown in Table 5, a comparison of Examples 10 to 12 with Comparative Example 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. [Industrial Applicability]

[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) Agrimony extract (B) Cellulose (C) Hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose

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

3. 3. The solid formulation according to claim 1, wherein the component (C) contains hydroxypropyl cellulose or hydroxypropyl methylcellulose.

4. 3. The solid preparation according to claim 1, wherein the ratio (A / C) of the content of component (A) to the content of component (C) is 0.3 to 20.

5. 3. The solid formulation according to claim 1 or 2, which is a tablet or capsule formulation.

6. 3. The solid preparation according to claim 1, which is a capsule preparation containing the component (C) in a 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 method contains the following component (C): (A) Agrimony extract (B) Cellulose (C) Hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose

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

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