JP2015140321A - Solid preparations for oral administration - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation for oral administration containing amino sugars, mucopolysaccharides, a vitamin P glycoside, and S-adenosyl L-methionine, and having storage stability and good flavor.SOLUTION: The present invention provides a solid preparation for oral administration containing yeast containing amino sugars, mucopolysaccharides, a vitamin P glycoside, and S-adenosyl L-methionine, and an acidulant.

Description

  The present invention relates to a solid preparation for oral administration.

  Conventionally, various functional components have been blended into foods, pharmaceuticals, and the like. In addition, a technique for reducing an unpleasant flavor caused by a functional component has been proposed.

Patent Document 1 includes glucosamine, chondroitin protein complex, and methylsaliphonylmethane as health foods for the purpose of supplementing ingredients for reducing or preventing bone or joint pain, and further, brewer's yeast, A health food containing functional ingredients such as hesperidin is disclosed.
Patent Document 2 discloses a preparation containing water-extracted chondroitin sulfate and quercetin glycoside as a preparation for oral administration that masks the bitterness derived from quercetin glycoside. Patent Document 3 discloses a preparation containing water-extracted chondroitin sulfate, quercetin glycoside, and milk flavor. Patent Documents 2 and 3 also disclose the content of glucosamine.

  S-adenosyl-L-methionine (hereinafter sometimes referred to as SAMe) is widely present in living tissues and is known as a substance involved in many biological reactions, and utilizes the physiological activity of SAMe. Therefore, various techniques have been proposed (see, for example, Patent Document 4). SAMe is known as an effective component for arthritis and the like. For example, for S-adenosyl-L-methionine (SAMe), yeast containing SAMe is frequently used as an intake source, and for example, some yeasts of the genus Saccharomyces cerevisiae contain SAMe at a high concentration.

JP 2004-113141 A International Publication No. 2010/013551 Pamphlet JP 2010-215520 A International Publication No. 2009/081833 Pamphlet

Among functional components that can be applied to solid preparations for oral administration, amino sugars, mucopolysaccharides, and vitamin P glycosides are all highly hygroscopic components. For this reason, when aminosaccharides, mucopolysaccharides, and vitamin P glycosides are included in solid preparations for oral administration such as granules and tablets, discoloration occurs over time, and hardness changes if the solid preparations are tablets. There is a problem that a phenomenon caused by moisture absorption, such as swelling, is likely to occur in a solid preparation.
As a result of examining the above problems, aminosaccharides, mucopolysaccharides, and vitamin P glycosides can be obtained by combining yeasts containing S-adenosyl-L-methionine with aminosaccharides, mucopolysaccharides, and vitamin P glycosides. It was found that the hygroscopicity of the body can be suppressed. However, there is also a new problem that the unique flavor of yeast has a problem of being avoided without meeting the user's preference.

  The present invention has been made in view of the above situation, and contains yeast containing amino sugar, mucopolysaccharide, vitamin P glycoside, and S-adenosyl-L-methionine, and has excellent storage stability and good quality. An object is to provide a solid preparation for oral administration having a flavor.

The present invention is as follows.
[1] A solid preparation for oral administration containing an amino sugar, a mucopolysaccharide, a vitamin P glycoside, a yeast containing S-adenosyl-L-methionine, and an acidulant.
[2] The solid preparation for oral administration according to [1], wherein the amino sugar is glucosamine or a salt thereof.
[3] The solid preparation for oral administration according to [2], wherein the glucosamine or a salt thereof is glucosamine hydrochloride.
[4] The oral administration according to any one of [1] to [3], wherein the content of yeast containing S-adenosyl-L-methionine relative to the amino sugar is 0.5% by mass to 35% by mass. Solid formulation.
[5] The solid for oral administration according to any one of [1] to [4], wherein the content of the acidulant with respect to the yeast containing S-adenosyl-L-methionine is 1% by mass to 60% by mass. Formulation.
[6] The solid preparation for oral administration according to any one of [1] to [5], wherein the mucopolysaccharide is chondroitin sulfate or a salt thereof.
[7] The solid for oral administration according to any one of [1] to [6], wherein the vitamin P glycoside is at least one selected from the group consisting of quercetin glycoside and hesperetin glycoside. Formulation.
[8] The oral administration according to any one of [1] to [7], wherein the sour agent is at least one selected from the group consisting of lactic acid, citric acid, ascorbic acid, malic acid, succinic acid, and tartaric acid. Solid formulation for administration.
[9] The solid preparation for oral administration according to any one of [1] to [8], wherein the solid preparation for oral administration is a tablet.

  According to the present invention, a solid for oral administration having storage stability and good flavor is obtained by containing a yeast containing aminosaccharide, mucopolysaccharide, vitamin P glycoside, and S-adenosyl-L-methionine. A formulation can be provided.

Hereinafter, the present invention will be described in detail.
In the present specification, a numerical range indicated using “to” indicates a range including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
In the present specification, the amount of each component in the composition means the total amount of the plurality of substances present in the composition unless there is a specific notice when there are a plurality of substances corresponding to each component in the composition. To do.
In this specification, the term “process” is not limited to an independent process, and is included in the term if the intended purpose of the process is achieved even when it cannot be clearly distinguished from other processes. .

[Solid formulation for oral administration]
The solid preparation for oral administration of the present invention contains an aminosaccharide, a mucopolysaccharide, a vitamin P glycoside, and a yeast containing S-adenosyl-L-methionine (hereinafter sometimes referred to as “SAMe-containing yeast” as appropriate). And the solid preparation for oral administration of this invention containing a sour agent becomes a solid preparation for oral administration which has storage stability and favorable flavor by containing said each component.

The “storage stability” in the solid preparation of the present invention means the stability when the solid preparation is stored over time.
In the solid preparation of the present invention, “good flavor” means that an unpleasant taste that the user feels in the oral cavity is suppressed when the solid preparation is orally administered. Here, “taste” includes both the perception of sweetness, salty taste, acidity, bitterness, pungent taste, and the like, and the perception of taste and odor as combined with flavor.

  In the present invention, by combining amino sugars, mucopolysaccharides, and vitamin P glycosides with SAMe-containing yeast, the hydrophobicity of the yeast acts and aminosaccharides, mucopolysaccharides, and vitamin P glycosides are combined. It is presumed that storage stability is improved by suppressing hygroscopicity resulting from the inclusion of saccharides. Furthermore, in the present invention, it is presumed that by combining the sour agent, the unique flavor of the SAMe-containing yeast is alleviated and a solid preparation having a good flavor can be obtained. However, the present invention is not bound by this assumption.

  As the dosage form of the solid preparation of the present invention, a dosage form is selected such that the composition that forms the solid preparation when orally administered is in direct contact with the oral cavity. Specific examples of the dosage form include tablets, granules, powders, etc. Tablets or granules are preferred, and tablets are more preferred. Tablets include orally disintegrating tablets.

<Amino sugar>
The solid preparation of the present invention contains an amino sugar.
In the present invention, the aminosaccharide means a monosaccharide having a hydroxyl group substituted with an amino group or a salt thereof, and a compound included in a polysaccharide having an amino group or a salt thereof. However, the aminosaccharide in the present invention does not include the mucopolysaccharide described later. Examples of aminosaccharide salts include hydrochlorides and sulfates.
An amino sugar may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of amino sugars include N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine, and salts thereof. Among them, as the amino sugar, from the viewpoint of the joint pain alleviation effect and the like, at least one selected from glucosamine or a salt thereof and N-acetylglucosamine is preferable, glucosamine or a salt thereof is more preferable, and glucosamine hydrochloride is further included. preferable.

  The content of aminosaccharides in the solid preparation is not particularly limited, but is preferably 10% by weight to 70% by weight of the total weight of the solid preparation from the viewpoint of the joint pain alleviation effect and the stability of the preparation. More preferably, it is 25 mass%-60 mass%, and it is still more preferable that it is 40 mass%-55 mass%.

<Mucopolysaccharide>
The solid preparation of the present invention contains mucopolysaccharide.
In the present invention, mucopolysaccharide means a polysaccharide containing an amino sugar (a sugar having a hydroxyl group substituted with an amino group).
Mucopolysaccharides may be used singly or in combination of two or more.

  Examples of mucopolysaccharides include, for example, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, keratan sulfate, and salts thereof, and polysaccharides such as chitin and chitosan. Among these, chondroitin sulfate or a salt thereof is preferable as the mucopolysaccharide from the viewpoint of the joint pain mitigating effect and the like. The mucopolysaccharide may be a complex with a protein.

  The content of the mucopolysaccharide in the solid preparation is not particularly limited, but is preferably 10% by mass to 15% by mass with respect to the total mass of the solid preparation from the viewpoint of the joint pain relieving effect and the stability of the preparation. .

<Vitamin P glycoside>
The solid preparation of the present invention contains vitamin P glycoside.
As the vitamin P glycoside, at least one selected from the group consisting of quercetin glycoside, hesperetin glycoside, naringenin glycoside, esculin glycoside, and esculene glycoside is preferably applied. Among them, the vitamin P glycoside is preferably at least one selected from the group consisting of quercetin glycosides and hesperetin glycosides from the viewpoints of joint pain alleviation and various physiological activities.

Vitamin P glycosides may be prepared according to methods described in known literature, or may be obtained as commercial products.
The quercetin glycoside can be produced, for example, by the method described in International Publication No. 2005/030975 pamphlet. Moreover, as a commercial item of a quercetin glycoside, "alphaG rutin" etc. which are marketed from Toyo Seika Co., Ltd. are mentioned.
The hesperetin glycoside can be prepared, for example, by the method described in JP2007-39349A. Moreover, as a commercial item of a quercetin glycoside, "Hayashibara Hesperidin S" etc. which are marketed from Hayashibara Co., Ltd. are mentioned.

  The content of vitamin P glycoside in the solid preparation is not particularly limited, but from the viewpoint of the joint pain alleviating effect and the stability of the preparation, 0.4% by mass to 2.5% by mass of the total mass of the solid preparation. It is preferable that

<Yeast containing S-adenosyl-L-methionine>
The solid preparation of the present invention contains yeast (SAMe-containing yeast) containing S-adenosyl-L-methionine.

  Since the solid preparation of the present invention has SAMe-containing yeast, excellent storage stability is obtained, and the effect of containing SAMe such as relief of joint inflammation is also expected.

Furthermore, when the solid preparation of the present invention contains SAMe-containing yeast, the effect of masking the salty taste of glucosamine hydrochloride can be obtained when glucosamine hydrochloride is contained as an amino sugar.
Among amino sugars, glucosamine hydrochloride has a strong salty taste. Therefore, when glucosamine hydrochloride is included, it may be avoided to orally administer the solid preparation due to its strong salty taste. In general, sweeteners are often used for masking salty tastes, but natural sweeteners are high in calories, and artificial sweeteners are used for natural products because of the recent trend toward natural products. There is a tendency to be avoided.
On the other hand, in the present invention, by containing the SAMe-containing yeast, the strong salty taste derived from glucosamine hydrochloride is masked even if substantially no sweetener is used (preferably without using a sweetener). can do.

  The SAMe-containing yeast in the present invention is not particularly limited as long as it is a yeast that produces SAMe in the cells. For example, the yeast preferably contains 1% by mass or more of SAMe per dry mass, more preferably the yeast contains 5% by mass or more of SAMe per dry mass, and contains 10% by mass or more of SAMe per dry mass. More preferably, it is yeast.

  As the origin of the SAMe-containing yeast, for example, yeast belonging to the genus Saccharomyces is preferable. More preferred is Saccharomyces cerevisiae K-6 strain (Sake Yeast Association No. 6; SAMe-containing sake yeast). Saccharomyces cerevisiae K-6 strain is available as NBRC2346 strain from National Institute of Technology and Evaluation.

  The SAMe-containing yeast may be a wild strain of the yeast described above or a mutant strain with improved mutation. Mutants can be obtained by methods well known to those skilled in the art, such as UV irradiation, treatment with drugs such as N-methyl-N′-nitro-N-nitrosoguanidine (NTG), ethyl methanesulfonate (EMS), and the like. . Furthermore, you may use the transformed microorganism produced so that SAMe can be produced highly using methods, such as gene recombination.

  SAMe-containing yeast produces and accumulates SAMe at a high concentration in the cell, then separates the yeast from the culture solution by a separation means such as centrifugation, and adds cyclodextrins to the resulting yeast cell concentrate After that, the cyclodextrin-encapsulating SAMe-containing yeast obtained by drying is preferable from the viewpoint that SAMe can be efficiently ingested. Examples of the yeast containing cyclodextrins include those disclosed in Japanese Patent No. 4479932. Cyclodextrins-containing SAMe-containing yeast is also available as a commercial product, and examples thereof include “SAMe-containing dry yeast” manufactured by Mitsubishi Gas Chemical Co., Ltd.

  SAMe-containing yeast may be used alone or in combination of two or more.

  The SAMe content in the SAMe-containing yeast is preferably 10% by mass or more because various functions expected of SAMe can be exhibited and effectiveness in reducing joint pain can be obtained. This content rate is calculated as a ratio (%) of the mass of SAMe contained in the yeast to the mass of the yeast in a state containing SAMe.

  The content (%) of the SAMe-containing yeast with respect to the amino sugar is preferably 0.5% by mass to 35% by mass from the viewpoint of storage stability and taste balance of the solid preparation, and is preferably 4% by mass to 25% by mass. % Is more preferable, and it is still more preferable that it is 7 mass%-17 mass%.

<Acidulant>
The solid preparation of the present invention preferably contains a sour agent.
By containing a sour agent, the unexpected effect that it can mask favorably with respect to the flavor resulting from SAMe containing yeast is acquired.

The acidulant is not particularly limited as long as it can impart sourness to food and drink, and a known acidulant can be suitably used. A sour agent may be used individually by 1 type, and may be used in combination of 2 or more type.
Examples of acidulants include adipic acid, fumaric acid, lactic acid, ascorbic acid, fruit extract, citric acid, succinic acid, malic acid, tartaric acid, gluconic acid, acetic acid, phosphoric acid and the like. Among these, as the sour agent, at least one selected from the group consisting of lactic acid, citric acid, ascorbic acid, malic acid, succinic acid, and tartaric acid is preferable from the viewpoint of realizing a good masking effect and preferable taste. From the viewpoint of good taste, at least one selected from lactic acid and ascorbic acid is more preferable, and lactic acid is still more preferable.

  The content of the acidulant with respect to the SAMe-containing yeast is preferably 1% by mass to 60% by mass, more preferably 5% by mass to 40% by mass, and more preferably 10% by mass to 20% from the viewpoint of taste exhibited by the solid preparation. More preferably, it is mass%.

<Other ingredients>
The solid preparation of the present invention may contain other components as needed in addition to amino sugar, mucopolysaccharide, vitamin P glycoside, SAMe-containing yeast, and acidulant.

<< sugar alcohol >>
The solid preparation of the present invention may contain a sugar alcohol.
Any sugar alcohol can be used without particular limitation as long as it has a function as a sweetener. Examples of sugar alcohols include monosaccharide alcohols such as erythritol, xylitol, and sorbitol; disaccharide alcohols such as maltitol, isomaltitol, lactitol, and reduced isomaltulose (reduced palatinose [registered trademark, hereinafter abbreviated]) Trisaccharide alcohols such as maltotriitol, isomaltoliitol, panitol, etc .; sugar alcohols such as oligosaccharide alcohols or more; sugar alcohols such as reduced starch syrup and powdered reduced maltose syrup.
Sugar alcohol may be used individually by 1 type, and may be used in combination of 2 or more type.
The content rate of sugar alcohol is suitably set according to the objective.

<< crystalline cellulose >>
The solid preparation of the present invention may contain crystalline cellulose.
Crystalline cellulose is a component mainly composed of a crystalline portion obtained by hydrolyzing natural cellulose with a mineral acid. Crystalline cellulose can further enhance the formability of the solid preparation, the masking effect of the flavor, and the like. As crystalline cellulose, what has arbitrary average particle diameters and bulk densities can be selected. A crystalline cellulose may be used individually by 1 type, and may be used in combination of 2 or more type.
Crystalline cellulose can be produced, for example, according to the method described in JP-A No. 11-152233, and a commercially available product can also be used. Examples of commercially available products include Theola ST-100, Theola FD-101, Theola FD-F20, Theola UF-F702, Theola FD-301 (trade names, all manufactured by Asahi Kasei Chemicals).
The crystalline cellulose content is appropriately set according to the purpose in consideration of desired moldability, flavor masking effect, and the like.

<< collagen peptide >>
The solid preparation of the present invention may contain a collagen peptide. A collagen peptide may be used individually by 1 type and may be used in combination of 2 or more type.

  As the collagen peptide, a collagen peptide having an average molecular weight of 3000 or less is preferably used. A collagen peptide having an average molecular weight of 3000 or less is a so-called collagen peptide sometimes referred to as low molecular weight collagen, and is considered to have various functions (for example, a joint pain relieving effect). On the other hand, collagen peptides with an average molecular weight of 3000 or less have a gelatinous unpleasant odor or a unique bitterness of collagen, so when blended into solid preparations such as granules and orally disintegrating tablets, they tend to be difficult to drink in terms of flavor. was there. However, the effect of improving the flavor in the solid preparation of the present invention is sufficiently exhibited even when a collagen peptide having an average molecular weight of 3000 or less is further used in combination.

  The average molecular weight of the collagen peptide can be confirmed using, for example, gel permeation chromatography (GPC). When calculating the average molecular weight by GPC, several types of polymers and polyethylene glycol (PEG) with different molecular weights that are known in advance are measured under the same conditions, and a calibration curve representing the relationship between the obtained retention time and the molecular weight of the polymer. And calculate based on it. The average molecular weight in the present invention refers to a weight average molecular weight calculated in terms of PEG according to this method.

  The collagen peptide is a protein obtained by hydrolyzing gelatin with an enzyme or an acid and containing a large amount of glycine, and is also available as a commercial product. The collagen may be collagen extracted from mammalian collagen tissue, or may be collagen extracted from fish collagen tissue, and is not particularly limited. Any collagen peptide can be appropriately selected depending on the application. For example, at least one of type I collagen peptide and type II collagen peptide may be used from the viewpoint of alleviating joint pain.

The content rate of the collagen peptide is appropriately set according to the purpose in consideration of various functions of the collagen peptide (for example, joint pain alleviation effect, etc.), flavor, and the like.
The content of the collagen peptide is preferably 0.1% by mass to 10% by mass, and preferably 0.1% by mass to 5% by mass, based on the total mass of the solid preparation.

<< Other optional ingredients >>
The solid preparation of the present invention may contain other optional components as shown below in addition to the above-described components.
Other optional components may be used alone or in combination of two or more.
As such an arbitrary component, generally, additives used in foods and drinks or pharmaceuticals can be used.
Other optional ingredients include, for example, porous silicon dioxide, sweeteners other than sugar alcohols such as artificial sweeteners, excipients, lubricants, colorants, preservatives, thickening stabilizers, antioxidants Agent, coloring agent, bleaching agent, fungicide, bitter agent, enzyme, brightener, seasoning, emulsifier, toughening agent, preparation agent, spice extract, flavor (peach flavor, milk flavor, matcha flavor, or coffee flavor ) And the like.

  Furthermore, the solid preparation of the present invention can contain a binder. The binder is not particularly limited, but from the viewpoint of obtaining granules having a desired particle size and particle size distribution, saccharides such as fructooligosaccharide, maltooligosaccharide, isomaltooligosaccharide, and galactooligosaccharide, and guar gum, pullulan, gum arabic, etc. A thickening polysaccharide etc. can be mentioned. A binder can be used individually or in combination of 2 or more types. Preferably, guar gum, pullulan, gum arabic or a combination of one or more of these having a high average molecular weight and little reducibility can be used.

[Method for producing solid preparation]
The solid preparation of the present invention is selected according to the dosage form using amino sugar, mucopolysaccharide, vitamin P glycoside, SAMe-containing yeast, acidulant, and other ingredients used as necessary. It can manufacture according to the manufacturing method of.

  Hereinafter, as a method for producing a solid preparation of the present invention, a method for producing a solid preparation having the form of granules and a method for producing a solid preparation obtained by tableting the granules will be described as examples. The manufacturing method of a solid formulation is not limited to this.

A solid preparation having the form of a granule is obtained by granulating a raw material composition containing amino sugar, mucopolysaccharide, vitamin P glycoside, SAMe-containing yeast, acidulant, and other ingredients used as necessary. It can obtain by the manufacturing method including the granulation process to obtain.
As the granulation method and the granulation conditions in the granulation step, the granulation method and the granulation conditions which are usually applied as a granule production method can be applied. In the present invention, granulation means that powdery raw material compositions are mixed and bonded to each other to form granules (granules) having a predetermined size and shape. The obtained granulated product may be any size or shape different from the size and shape in the raw material composition.

It is preferable that a granulation process includes granulating a raw material composition on the temperature conditions of 70 to 100 degreeC.
From the viewpoint of making it easier to achieve the desired particle formation, the granulation temperature is preferably 75 ° C to 95 ° C, more preferably 80 ° C to 90 ° C.

  The granulation time is generally 0.01 hours to 3 hours in order to granulate into a desired shape, and within a range of 0.1 hours to 2 hours from the viewpoint of improving flavor and suppressing the generation of by-products. Preferably, it is 0.2 hours to 1 hour, more preferably 0.3 hours to 1.0 hour.

  The granulation is performed by mixing the raw material composition (powder) or a part thereof, heating the resulting mixture under the above-described temperature conditions, and drying. Examples of the granulation method include stirring granulation, extrusion granulation, fluidized bed granulation and the like, and fluidized bed granulation is preferable from the viewpoint of productivity. The heating means is not particularly limited as long as it can heat the inside of the apparatus so that the raw material composition satisfies the above temperature conditions.

  In granulation, it is preferable to use a binder liquid containing a binder. The binder liquid is preferably attached to the powdery raw material composition by spraying. Examples of the binder include the components described above. The solvent for constituting the binder liquid may be an aqueous solvent, and examples thereof include water and ethanol. In general, the binder content in the binder liquid is preferably 0.1% by mass to 1% by mass.

  It is preferable that the binder liquid used at the time of granulation is 10 mass parts-20 mass parts with respect to 100 mass parts of raw material compositions from a viewpoint of obtaining a desired shape and granulation efficiency.

Drying is performed after spraying until the optimum moisture content is reached. The water content in this case is not necessarily the same as the water content of the final chewable tablet to be described later, and can be set based on the presence and type of the manufacturing process after the drying process.
The water content in the granulated product after the drying step is generally 2% by mass to 4% by mass, and it is common to absorb moisture until tableting or the subsequent packaging step into the product form. The water content at the end of granulation is preferably 2 to 3% by mass, which is lower.

The drying conditions may be those normally used for achieving an optimal moisture content. For example, the drying time is preferably 0.01 hours to 2 hours, preferably from the viewpoint of preventing re-disintegration of granules after granulation. 0.02 hours to 1 hour is applied.
About the size of the granulated product obtained in these series of granulation steps, generally, the maximum diameter of the projected area of the granulated product is a granular material of 100 μm to 1000 μm, and preferably has a maximum diameter of 150 μm to 500 μm. Although it is a granular material, it is not particularly limited in the present invention.

  In the present invention, the granulated product obtained by the granulation step may be tableted for subsequent molding into a desired shape. Thereby, a solid preparation having a desired size and shape can be obtained. The granulation step and the tableting step are not necessarily clearly distinguished, and may be performed continuously. As a tableting method, a method generally applied for this purpose may be applied as it is, and there is no particular limitation. Moreover, you may perform tableting integrally with the granulation mentioned above like compression granulation. There is no restriction | limiting in particular as temperature at the time of tableting, when carrying out as another process after granulation, For example, what is necessary is just to follow according to normal conditions, such as 20 to 40 degreeC.

In the case of tableting, if there is a remaining raw material composition that has not been added in the granulation step, this remaining raw material composition may be added.
As a raw material composition that is preferably added after granulation, it is necessary at the time of tableting molding of SAMe-containing yeast from the viewpoint of preventing changes in ingredients during granulation, or from the viewpoint of preventing deterioration of fragrance during granulation. Lubricants which are various raw materials.
In addition to the steps described above, other steps may be included as necessary.

  The shape of the solid preparation that is a tablet is not particularly limited, such as a spherical shape, a rugby ball shape, or a disk shape. The maximum diameter, thickness, and the like of the tablet are appropriately selected in consideration of ease of swallowing and the like.

The hardness of the resulting tablet is not particularly limited, but is preferably 25N or more and 110N or less, more preferably 35N or more and 100N or less, and most preferably 45N or more and 90N or less from the viewpoint of transport stability and the like. Moreover, the hardness of a tablet can be measured with a tablet breaking strength measuring instrument.
The hardness of the tablet can be appropriately adjusted by adjusting the tableting pressure when tableting the granulated powder.

  Although there is no restriction | limiting in particular in the moisture content of the tablet obtained, It is preferable that it is 5 mass% or less, and it is more preferable that it is 2 mass% or more and 4 mass% or less. Although the moisture content of the tablet in the present invention is measured by the absolutely dry method, it is not limited thereto. In the absolute dry method, a sample to be measured is collected in a sealed container, sealed and measured for the total mass, then opened and the container containing the sample is placed in a dryer and dried at 105 ° C. for 4 hours. Then, it is taken out from the dryer, immediately sealed, cooled to room temperature, sealed again, the total mass is measured, and the value shown by the change in mass before and after drying is taken. The moisture content of the tablet can be adjusted as appropriate by controlling the drying temperature after granulating the raw material powder, the time, the humidity environment when handling the powder, and the tablet.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to them at all. Unless otherwise specified, “%” and “part” are based on mass.

[Example 1]
(Preparation of granules)
As a raw material composition, a powder component having a blending ratio (%) shown in Table 1 was put in a fluidized bed granulator (flow coater, manufactured by Freund Sangyo Co., Ltd.) and heated and mixed at a hot air temperature of 85 ° C. 15.4 parts by mass of a binder liquid of 0.3% by mass of guar gum was sprayed on 100 parts by mass of the powder component and granulated (size of granulated product: 94 μm of particles of 150 μm to 500 μm of all particles) %). Thereafter, the obtained granulated product was dried at a hot air temperature of 85 ° C. until the water content became 2.5 mass%. The granulated product after drying was returned to room temperature (25 ° C.) to obtain granules.

(Preparation of tablets)
The obtained granules were tableted with a rotary tableting machine to obtain disc-shaped tablets having a mass of 300 mg, a diameter of 9 mm, and a hardness of 70 N.

[Examples 2-4, 6-21, Comparative Examples 1-2, 4]
A granule was prepared in the same manner as in Example 1 except that the blending ratio of the powder component was changed to the blending ratio shown in Table 1 or Table 2, and then the obtained granule was tableted to obtain a tablet. .

[Example 5]
A granule was obtained in the same manner as in the preparation of the granule in Example 1, except that the blending ratio of the powder component was changed to the blending ratio shown in Table 1.

[Comparative Example 3]
A granule was obtained in the same manner as in the preparation of the granule in Example 1, except that the blending ratio of the powder component was changed to the blending ratio shown in Table 1. Next, 300 mg of the obtained granule was filled into a capsule made of gelatin to obtain a hard capsule.

<Yeast / Amino sugar (%)>
About Examples 1-21 and Comparative Examples 1 and 4, the content rate (%) of SAMe containing yeast with respect to the used amino sugar was computed, and it showed in Table 1 or Table 2.
For Comparative Examples 2 and 3, the content (%) of brewer's yeast relative to the aminosaccharide used was calculated and shown in Table 1 or Table 2.

<Acidulant / yeast (%)>
About Examples 1-21 and Comparative Examples 1 and 4, the content rate (%) of the sour agent with respect to the used SAMe containing yeast was computed, and it showed in Table 1 or Table 2. FIG.
About the comparative examples 2 and 3, the content rate (%) of the sour agent with respect to the used brewer's yeast was computed, and it showed in Table 1 and Table 2. FIG.

  Details of the powder components shown in Tables 1 and 2 are as follows.

(Amino sugar)
Glucosamine hydrochloride: “Koyo Glucosamine” (Koyo Chemical Co., Ltd.)
N-acetylglucosamine: “Marine Sweet” (Yaizui Fisheries Chemical Co., Ltd.)

(Mucopolysaccharide)
Hyaluronic acid: "Hear best J" (Kupy Corporation)
Chondroitin sulfate-containing protein complex: “SCP” (Maruha Nichiro Foods, Inc.)

(Vitamin P glycoside)
Quercetin glycoside: “αG rutin” (Toyo Seika Co., Ltd.)
Hesperetin glycoside: “Hayashibara Hesperidin S” (Hayashibara Co., Ltd.)

(SAMe-containing yeast)
SAMe-containing yeast: “SAMe-containing dry yeast” (Mitsubishi Gas Chemical Co., Ltd.) (SAMe content in yeast is 10% by mass or more per dry mass)
(Beer yeast (comparison yeast))
Beer yeast: “Powder beer yeast” (Asahi Food and Healthcare Co., Ltd.)

(Acidulant)
Lactic acid (Showa Processing Co., Ltd.)
Citric acid (Showa Processing Co., Ltd.)
Ascorbic acid (Chugai Pharmaceutical Co., Ltd.)
Malic acid (Showa Processing Co., Ltd.)
Succinic acid (Nippon Shokubai Co., Ltd.)
Tartaric acid (Showa Processing Co., Ltd.)

(Other ingredients)
Type II collagen peptide: “P-mucolla” (Nippon Ham Co., Ltd.)
Crystalline cellulose: “Theolas FD101” (Asahi Kasei Chemicals Corporation)
Fine silicon oxide: “Carplex FPS-500” (DSL Japan)
Calcium stearate: “SAK-CS-P-1 / USP” (San Ace Co., Ltd.)

<Evaluation test>
(1) Storage stability Each tablet obtained in Examples 1 to 4 and 6 to 21, each tablet obtained in Comparative Examples 1 to 2 and 4 and the granule obtained in Example 5 were mixed at 40 ° C. It was aged for 7 days under constant temperature and humidity conditions of 75% humidity. Tablets or granules before and after aging were used as samples for evaluation.
The tablets were evaluated for storage stability based on discoloration, hardness and diameter. The granule was evaluated for storage stability by discoloration. The results are shown in Table 1 or Table 2.

i) Discoloration The discoloration of the evaluation sample (tablet or granule) after the lapse of time was visually evaluated as to whether it was acceptable as a food. Evaluation was according to the following criteria.
1: Discoloration progresses greatly from before aging and is not acceptable as food.
2: Although discoloration has progressed from before aging, it is accepted as food.
3: Discolored slightly before aging, but no problem as food.
4: There is almost no change from the color with the sample before aging.

ii) Hardness The hardness of the evaluation sample (tablet) was measured using a tablet breaking strength measuring instrument (TH-203MP manufactured by Toyama Sangyo Co., Ltd.).
It was observed that the tablet hardness decreased with time.
When the tablet hardness is less than 50 N, it is determined that there is a greater concern about chipping and cracking.

iii) Diameter The diameter of the sample (tablet) for evaluation after time was measured using a caliper. A tablet having a diameter of 11 mm or more is judged to be poor in appearance.

(2) Flavor When each tablet obtained in Examples 1 to 4 and 6 to 21, each tablet obtained in Comparative Examples 1 to 2 and 4 and the granule obtained in Example 5 were administered into the mouth The taste (salt taste, flavor, acidity) felt was evaluated according to the following criteria by 20 subjects. The most opinion was taken as the evaluation result. The results are shown in Table 1 or Table 2.
(Salty)
1: It feels very salty and is unacceptable as a food.
2: Feels somewhat salty, but is acceptable as a food.
3: Almost no salty taste.
(Flavor)
1: Unpleasant flavor, unacceptable as food 2: Feeling flavor, but acceptable as food 3: Feeling a little flavor, but no problem as food 4: Slightly unseen flavor (acidity )
1: It has an unpleasant acidity and is not acceptable as a food.
2: Although it feels sour, it is acceptable as a food.
3: Slightly sour, but no problem for food.
4: Almost no acidity.

(3) Ease of swallowing Each tablet obtained in Examples 1-4 and 6-21, each tablet obtained in Comparative Examples 1-2, 4 and hard capsules obtained in Comparative Example 3, Examples The granule obtained in 5 was swallowed by 20 test subjects, and interviews were conducted on the ease of swallowing. Evaluation was made according to the following criteria. The most opinion was taken as the evaluation result. The results are shown in Table 1 or Table 2. A: Easy to swallow B: Difficult to swallow

(4) Functionality evaluation About the tablet obtained in Example 3 and the hard capsule obtained in Comparative Example 3, each subject having knee joint pain ingested 5 tablets per day for 1 month, A hearing was conducted regarding the improvement of symptoms.
Both the tablet obtained in Example 3 and the hard capsule obtained in Comparative Example 3 were effective in reducing joint pain, but the tablet in Example 3 was more effective than the hard capsule in Comparative Example 3. It was effective by improvement. This result is presumed to be because the formulation of Example 3 contained SAMe-containing yeast, and the joint pain improving effect was further improved as compared with Comparative Example 3 containing beer yeast.

From the results of Table 1 and Table 2, it can be seen that all of the solid preparations of Examples 1 to 21 are solid preparations having excellent storage stability and a good flavor. Such a solid preparation is not obtained in the comparative example. Moreover, it turns out that the solid formulation of an Example is a tablet or a granule, and all are easy to swallow and a flavor is also favorable. On the other hand, it can be seen that Comparative Example 3, which is a hard capsule, is difficult to swallow.

  From these results, according to the present invention, a solid containing amino sugar, mucopolysaccharide, vitamin P glycoside, and yeast containing S-adenosyl-L-methionine, having storage stability and good flavor. A formulation can be provided.

Claims (9)

  A solid preparation for oral administration containing an amino sugar, a mucopolysaccharide, a vitamin P glycoside, a yeast containing S-adenosyl-L-methionine, and an acidulant.   The solid preparation for oral administration according to claim 1, wherein the amino sugar is glucosamine or a salt thereof.   The solid preparation for oral administration according to claim 2, wherein the glucosamine or a salt thereof is glucosamine hydrochloride. The yeast content containing S-adenosyl-L-methionine relative to the amino sugar is
It is 0.5 mass%-35 mass%, The solid formulation for oral administration of any one of Claims 1-3.   The solid preparation for oral administration according to any one of claims 1 to 4, wherein the content of the acidulant with respect to the yeast containing S-adenosyl-L-methionine is 1% by mass to 60% by mass.   The solid preparation for oral administration according to any one of claims 1 to 5, wherein the mucopolysaccharide is chondroitin sulfate or a salt thereof.   The solid preparation for oral administration according to any one of claims 1 to 6, wherein the vitamin P glycoside is at least one selected from the group consisting of quercetin glycoside and hesperetin glycoside.   The sour agent is at least one selected from the group consisting of lactic acid, citric acid, ascorbic acid, malic acid, succinic acid, and tartaric acid. Solid for oral administration according to any one of claims 1 to 7. Formulation.   The solid preparation for oral administration is a tablet, according to any one of claims 1 to 8.