JP2014047183A - Granule and manufacturing method of the same, and tablet and manufacturing method of the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a granule and a manufacturing method of the same, and a tablet and a manufacturing method of the same which can suppress blocking in a granulation step and can also suppress sticking in a compression step while containing at least one material selected from a water absorptive amino acid or its salt, and yeast extracts, and which enable easy manufacturing in a short time.SOLUTION: A manufacturing method of a granule of which water absorption inhibitor is silicate comprises the steps of: mixing at least one material selected from a water absorptive amino acid or its salt, and yeast extracts with the water absorption inhibitor; and granulating the mixture obtained by the mixing step.

Description

  The present invention relates to a granule containing at least one selected from a water-absorbing amino acid or a salt thereof and a yeast extract and a method for producing the same, and at least one selected from a water-absorbing amino acid or a salt thereof and a yeast extract. The present invention relates to a seed-containing tablet and a method for producing the same.

  In recent years, with increasing awareness of irregular diets and beauty, there is an increasing demand for dietary supplements and supplements containing nutrients such as amino acids, vitamins, and minerals in order to efficiently supply the necessary nutrients. . Further, as these dosage forms, tablets that can be taken easily are preferred.

  Conventionally, tablets containing a water-absorbing amino acid or yeast extract have a problem that sticking occurs in the tableting process due to the water-absorbing property of the water-absorbing amino acid or yeast extract. So far, in order to solve the above-mentioned problem, a method has been proposed in which granules containing a water-absorbing amino acid are coated with an ethanol-soluble and poorly water-soluble coating agent, and the coated granules are used in a tableting process (for example, , See Patent Document 1). However, the proposal has problems that the work process is complicated and that it takes a long time to produce a tablet.

  On the other hand, in the granulation process, granulation is performed using various powders. At this time, if the particle size of the powder is different, the fluidity of the powder is lowered, and as a result, the resulting granule becomes non-uniform. May be frustrated. Therefore, a fluidizing agent (sometimes referred to as a fluidizing aid or anti-caking agent) is used to prevent the powder fluidity from being lowered. As one of the fluidizing agents, silicic acid is used. Salt is known.

  So far, even if it contains a water-absorbing amino acid or yeast extract, granules that can be easily produced in a short time and can suppress sticking and the like in the tableting process, and its production method, and Tablets and methods for producing the tablets have not yet been provided, and rapid development is required.

International Publication No. 2004/078171

  An object of the present invention is to solve the above-described problems and achieve the following objects. That is, the present invention can suppress blocking in the granulation step even if it contains at least one selected from water-absorbing amino acids or salts thereof and yeast extracts, An object of the present invention is to provide a granule that can suppress sticking and can be easily produced in a short time, a method for producing the same, a tablet, and a method for producing the same.

  In order to solve the above problems, the present inventors have conducted intensive studies. As a result, when at least one selected from a water-absorbing amino acid or a salt thereof and a yeast extract is added, in addition to sticking in the tableting process, The problem of blocking in the grain process was also found. To solve these problems, silicate known as a powder fluidizing agent is mixed with at least one selected from a water-absorbing amino acid or a salt thereof, and yeast extract in the step before the granulation step. As a result, it was found that blocking in the granulation step can be unexpectedly suppressed, and further sticking in the tableting step can be suppressed.

Means for solving the problems are as follows. That is,
<1> a step of mixing a water-absorbing amino acid or a salt thereof and at least one selected from yeast extracts and a water absorption inhibitor;
And granulating the mixture obtained in the mixing step,
The method for producing granules, wherein the water absorption inhibitor is a silicate.
<2> The amount of the silicate with respect to at least one selected from water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). At least one selected from the group consisting of 0.01 to 10.0.
<3> The water-absorbing amino acid or salt thereof, and at least one selected from yeast extracts includes at least one of arginine-glutamate and glutamic acid, according to any one of <1> to <2>. It is a manufacturing method of a granule.
<4> Any one of <1> to <3>, further comprising at least one water-absorbing amino acid or an amino acid other than a salt thereof or a salt thereof, at least one vitamin, and at least one mineral. The method for producing a granule as described in 1. above.
<5> The method for producing a granule according to any one of <1> to <4>, wherein the granule is not coated with a coating agent.
<6> A granule produced by the production method according to any one of <1> to <5>.
<7> containing at least one water-absorbing amino acid or salt thereof, and yeast extract, and a water absorption inhibitor,
The water absorption inhibitor is a silicate;
The amount of the silicate with respect to at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). It is a granule characterized by being 0.01 to 10.0.
<8> The water-absorbing amino acid or salt thereof, and at least one selected from yeast extracts includes at least one of arginine-glutamate and glutamic acid, according to any one of <6> to <7>. It is a granule.
<9> Any one of <6> to <8>, further comprising at least one water-absorbing amino acid or an amino acid other than a salt thereof or a salt thereof, at least one vitamin, and at least one mineral. It is a granule as described in.
<10> The granule according to any one of <6> to <9>, wherein the granule is not coated with a coating agent.
<11> a step of mixing a water-absorbing amino acid or a salt thereof and at least one selected from yeast extracts and a water absorption inhibitor;
Granulating the mixture obtained in the mixing step;
Tableting the granules obtained in the granulation step,
A method for producing a tablet, wherein the water absorption inhibitor is a silicate.
<12> The amount of silicate with respect to at least one selected from water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). The method for producing a tablet according to <11>, which is 0.01 to 10.0.
<13> The water-absorbing amino acid or a salt thereof, and at least one selected from yeast extracts includes at least one of arginine-glutamate and glutamic acid, according to any one of <11> to <12>. It is a manufacturing method of a tablet.
<14> Any one of <11> to <13>, further comprising at least one water-absorbing amino acid or an amino acid other than a salt thereof or a salt thereof, at least one vitamin, and at least one mineral A method for producing a tablet as described in 1. above.
<15> The method for producing a tablet according to any one of <11> to <14>, wherein the granules are not coated with a coating agent.
<16> The method for producing a tablet according to any one of <11> to <15>, wherein the tablet is not sugar-coated.
<17> A tablet produced by the production method according to any one of <11> to <16>.
<18> containing at least one water-absorbing amino acid or salt thereof, and yeast extract, and a water absorption inhibitor,
The water absorption inhibitor is a silicate;
The amount of the silicate with respect to at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). It is a tablet characterized by being 0.01 to 10.0.
<19> The water-absorbing amino acid or salt thereof, and at least one selected from yeast extracts includes at least one of arginine-glutamate and glutamic acid, according to any one of the above <17> to <18>. It is a tablet.
<20> Any one of the above <17> to <19>, further comprising at least one water-absorbing amino acid or an amino acid other than a salt thereof, or a salt thereof, at least one vitamin, and at least one mineral It is a tablet of description.
<21> The tablet according to any one of <17> to <20>, wherein the granule is not coated with a coating agent.
<22> The tablet according to any one of <17> to <21>, wherein the tablet is not sugar-coated.

  According to the present invention, the above-described problems can be solved and the object can be achieved, and even if it contains at least one selected from a water-absorbing amino acid or a salt thereof and yeast extract, Granules capable of suppressing blocking in the granule process, and also capable of suppressing sticking in the tableting process, which can be easily produced in a short time, a method for producing the same, and a tablet and a method for producing the same Can be provided.

FIG. 1 is a diagram illustrating an example of blocking in the granulation step of Test Example 1. FIG. 2 is a diagram illustrating an example of sticking in the tableting process of Test Example 1.

(Granule and production method thereof)
The granule of the present invention contains at least one selected from a water-absorbing amino acid or a salt thereof, and yeast extracts and a water absorption inhibitor, and further contains other components as necessary.
There is no restriction | limiting in particular as a manufacturing method of the granule of this invention, Although it can select suitably according to the objective, The manufacturing method of the granule of this invention is preferable.
Hereinafter, the granule of the present invention will be described together with the description of the method for producing the granule of the present invention.

<Granule production method>
The granule production method of the present invention includes at least a mixing step and a granulation step, and further includes other steps as necessary.

<< Mixing process >>
The mixing step is a step of mixing at least one selected from a water-absorbing amino acid or a salt thereof and yeast extract and a water absorption inhibitor, and if necessary, further mixing other components. Good. By mixing at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts and the water absorption inhibitor, blocking in the granulation step described later can be suppressed and obtained. The sticking in the tableting process when manufacturing a tablet using the granule can be suppressed.
In the present specification, for the sake of convenience, the mixing step and the granulation step are described separately, but at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts, Mixing with a water absorption inhibitor should just be performed before granulating.
The mixing step may be performed in one step, or may be performed in two or more steps.
There is no restriction | limiting in particular as said mixing method, It can mix by a conventional method. For the mixing, an apparatus can be used. Examples of the apparatus include a container tumbler (manufactured by Yamazaki Metal Industry Co., Ltd.), a V-type mixer (manufactured by Tokuju Kogyo Co., Ltd.), and a Bole container mixer (manufactured by Kotobuki Kogyo Co., Ltd.). Company-made).

  There is no restriction | limiting in particular as temperature of the said mixing process, Although it can select suitably according to the objective, 10 to 35 degreeC is preferable and 15 to 30 degreeC is more preferable. If the temperature of the mixing step is less than 10 ° C, condensation may occur and the raw material may be wetted. If it exceeds 35 ° C, the stability of each component may be affected.

  There is no restriction | limiting in particular as time of the said mixing process, Although it can select suitably according to the objective, 5 minutes-50 minutes are preferable and 10 minutes-40 minutes are more preferable. When the time of the mixing step is less than 5 minutes, the raw materials may not be uniformly mixed. When the mixing time exceeds 50 minutes, classification may occur due to the difference in particle size, and the uniform state may be lost.

-Water-absorbing amino acid or salt thereof-
The water-absorbing amino acid refers to an amino acid having a property of absorbing water well, a property of absorbing or absorbing moisture or moisture in the air, and a property of exhibiting deliquescence and stickiness by absorbing a small amount of water or moisture.
Specific examples of the water-absorbing amino acid include arginine, glutamic acid, proline, lysine, histidine, cysteine (including cystine), ornithine and the like.
The salt of the water-absorbing amino acid is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include salts with inorganic acids or organic acids such as hydrochloride, sulfate and acetate, sodium salts, potassium Examples include salts with bases such as salts, and specific examples include arginine-glutamate and lysine hydrochloride.
The water-absorbing amino acid may be a salt thereof, or a water-absorbing amino acid and a salt thereof may be used in combination.
The granule may contain at least one of the water-absorbing amino acids or salts thereof, but preferably contains at least one of arginine-glutamate and glutamic acid.

-Yeast extracts-
The yeast extracts are those obtained by extracting useful components in yeast by self-digestion, enzymes, hot water treatment, and the like, and include those containing amino acids, nucleic acid-related components, minerals, and vitamins.
Specific examples of the yeast extract include thiamine-containing yeast extract, peptide-containing yeast extract, cysteine peptide-containing yeast extract, nucleic acid-rich yeast extract, and glutamic acid-rich yeast extract.

  The content of at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts in the granules is not particularly limited and can be appropriately selected depending on the amount to be contained in the tablet. It is preferable that 0.1% by mass to 90% by mass is contained per granule, more preferably 0.5% by mass to 85% by mass, and particularly preferably 1.0% by mass to 80% by mass. preferable.

-Water absorption inhibitor-
The appearance change inhibitor is silicate.
The silicate is not particularly limited and can be appropriately selected according to the purpose. Examples thereof include calcium silicate, magnesium silicate, aluminum metasilicate, magnesium aluminate metasilicate, magnesium aluminate silicate, and the like. Can be mentioned. Among these, calcium silicate is preferable.

There is no restriction | limiting in particular as a median diameter (d50) of the said calcium silicate, Although it can select suitably according to the objective, 18 micrometers-32 micrometers are preferable.
There is no restriction | limiting in particular as a loose bulk density of the said calcium silicate, Although it can select suitably according to the objective, 0.07 g / mL-0.15 g / mL are preferable.
There is no restriction | limiting in particular as oil absorption amount of the said calcium silicate, Although it can select suitably according to the objective, 300 mL / 100g-550 mL / 100g is preferable.
Examples of calcium silicate satisfying the median diameter (d50), loose bulk density, and oil absorption include calcium silicate represented by the following formula (1).
2CaO · mSiO ₂ · nH ₂ O Formula (1)
However, in the formula (1), 1 <m <2 and 2 <n <3.
As a commercial item of the said calcium silicate, Florite R (made by Tomita Pharmaceutical Co., Ltd.) is mentioned, for example.

  There is no restriction | limiting in particular as content of the said silicate, Although it can select suitably according to the objective, When it is set as a tablet, it is 0.01 mass%-10 mass% per tablet. It is preferable to prepare, more preferably 0.05 mass% to 5.0 mass%, and particularly preferably 0.1 mass% to 2.0 mass%.

-Mass ratio of at least one selected from water-absorbing amino acids or salts thereof and yeast extracts and silicate-
There is no restriction | limiting in particular as an amount of the silicate with respect to at least 1 sort (s) selected from the water absorbing amino acid or its salt in the said granule, and yeast extract, Although it can select suitably according to the quantity when it is set as a tablet. Per granule, in mass ratio (at least one selected from silicate / water-absorbing amino acid or salt thereof, and yeast extract), preferably 0.01 to 10.0, 0.1 to 5.0 Is more preferable, and 0.2 to 2.0 is particularly preferable.

<< Granulation process >>
The granulation step is a step of granulating the mixture obtained in the mixing step. In the granulation step, other components may be added as necessary.
The granulation method is not particularly limited as long as the mixture is granulated, and a known method can be appropriately selected according to the purpose. For example, fluidized bed granulation method, stirring granulation method, dry method Examples thereof include a granulation method. Among these, the fluidized bed granulation method is preferable.

As one aspect of the granulation method, kneading, kneading the mixture, and, if necessary, other components (hereinafter sometimes referred to as “granulation powder”), and A method of stirring and spraying a suitably selected thickener may be mentioned.
The thickener is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include pullulan; sugar alcohols such as xylitol, sorbitol, mannitol and maltitol; trehalose; disaccharides such as palatinose and isomalt; Examples thereof include cellulose derivatives such as hydroxypropylcellulose and hydroxypropylmethylcellulose; dextrin; and gums such as guar gum.

The thickener is preferably a solution or dispersion (hereinafter sometimes referred to as “a spray solution”) for spraying.
There is no restriction | limiting in particular as a solvent used in order to melt | dissolve thru | or disperse | distribute the said thickener, Although it can select suitably according to the kind etc. of thickener to be used, Water, ethanol, etc. are mentioned, for example.

There is no restriction | limiting in particular as a viscosity of the said spraying liquid, According to the objective, it can select suitably.
There is no restriction | limiting in particular as a density | concentration (solid content density | concentration) of this thickener in the said spraying liquid, According to the objective, it can select suitably.
There is no restriction | limiting in particular as the spraying quantity of the said spraying liquid, According to the said viscosity, a density | concentration, etc., it can select suitably.

There is no restriction | limiting in particular as the method of spraying the said spraying liquid, According to the objective, it can select suitably, For example, it sprays from the spray means provided in the granulation apparatus to be used, for example, a spray gun, a spray nozzle, etc. The method of performing etc. is mentioned suitably.
At this time, the spraying conditions are not particularly limited, and known conditions can be adopted. The spraying amount, the size of the sprayed mist particles (mist), the spraying time, the spraying can be adopted according to the purpose. An interval or the like can be appropriately selected.

  There is no restriction | limiting in particular as an apparatus used for the said granulation, According to the objective, it can select suitably according to the objective from a well-known granulation apparatus (for example, rolling fluid coating apparatus-MP, for example) -01 (manufactured by POWREC Co., Ltd.), etc.), centrifugal flow type coating granulator (eg, Granurex (manufactured by Freund Sangyo Co., Ltd.)), composite type granulating coating device (eg, Spiraflow (manufactured by Freund Sangyo Co., Ltd.)) ), Etc.), fluidized bed granulator / dryer (eg, GPCG / WSG-CT series (manufactured by POWREC Co., Ltd.)), flow coater (manufactured by Freund Sangyo Co., Ltd.), fine particle coating / granulating apparatus-SFP series (manufactured by (Paulec), fine particle coating equipment GPCG-SCP series (Paulec Co., Ltd.), mixing Granulator (e.g., Vertical Granulator (Co. Powrex), and the like) and the like are preferably exemplified. Among these, a rolling fluid coating apparatus and a fluidized bed granulation drying apparatus are preferable.

  There is no restriction | limiting in particular as supply temperature of the said granulation process, Although it can select suitably according to the objective, 50 to 100 degreeC is preferable and 65 to 90 degreeC is more preferable. If the air supply temperature is less than 50 ° C., the drying efficiency of the granule during the granulation step is poor, the granule is too wet and granulation proceeds too much (the granule becomes too large), or blocking occurs. If the temperature exceeds 100 ° C., the stability of various components in the tablet may be impaired, and the granulation powder may be burnt.

  There is no restriction | limiting in particular as exhaust temperature of the said granulation process, Although it can select suitably according to the objective, 20 to 45 degreeC is preferable and 25 to 40 degreeC is more preferable. When the exhaust temperature is less than 20 ° C, the drying efficiency of the granule during the granulation step is poor, the granule is too wet and granulation proceeds too much, blocking may occur, and the like. If it exceeds 1, granulation may not proceed and granules having the intended particle size may not be obtained.

  There is no restriction | limiting in particular as time of the said granulation process, Although it can select suitably according to the objective, 15 minutes-50 minutes are preferable, and 20 minutes-40 minutes are more preferable. If the granulation time is less than 15 minutes, granulation may be insufficient and a particle having the desired particle size may not be obtained. If it exceeds 50 minutes, the desired particle size of the granule may be obtained. May be larger.

The median diameter (d50) of the granule obtained in the granulation step (hereinafter also referred to as a granulated product) is not particularly limited and may be appropriately selected depending on the intended purpose, but is 100 μm to 700 μm. Preferably, 150 μm to 400 μm is more preferable.
The median diameter (d50) can be measured with a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.).

<< Other processes >>
The other steps are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. Examples thereof include a pulverization step and a drying step.

-Crushing process-
The pulverizing step is a step of pulverizing in advance in order to control the particle size of the granulated product to be not too large before the granulating step.
The pulverizing method is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a pulverizing granulator (Power Mill, manufactured by Dalton Co., Ltd.) and a Super Clean Mill (manufactured by Nara Machinery Co., Ltd.). Etc.

-Drying process-
The drying step is a step of drying the granule after the granulation step. By passing through the drying step, it is advantageous in that the handleability is improved in the tableting step performed when the tablet is produced.
The drying method is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include an air drying method and a heat drying method.

<Granule>
The granule of the present invention can be suitably produced by the above-described method for producing a granule of the present invention.
Since the granule of this invention can suppress blocking in the granulation process, it can be easily manufactured in a short time. Moreover, since the sticking in the tableting process at the time of manufacture can be suppressed when the said granule is used for the tablet mentioned later, it can use suitably as a raw material of a tablet.

The granule may be coated or uncoated, but it is preferable that the granule is not coated because the granule can be produced easily and in a short time.
The coating of the granules can be confirmed, for example, by observation with an electron microscope.

<< Other ingredients >>
The other component in the granule is not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. For example, an amino acid other than the water-absorbing amino acid or a salt thereof or a salt thereof, Vitamins, minerals, functional ingredients, various polyphenols, lubricants, disintegrants, excipients, binders, binders, colorants, pH adjusters, buffers, antioxidants, and the like can be mentioned.
In addition to at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts, the granule of the present invention further comprises at least one amino acid other than the water-absorbing amino acids or salts thereof, or salts thereof, and at least one. Preferably it contains seed vitamins and at least one mineral.
There is no restriction | limiting in particular as long as the effect of this invention is impaired as time to add the said other component, According to the objective, it can select suitably.
The other components may be added all at once, or may be added in a plurality of times.
There is no restriction | limiting in particular as a state of the raw material of the said other component, According to the objective, it can select suitably.

-Amino acids other than water-absorbing amino acids or salts thereof or salts thereof-
There is no restriction | limiting in particular as amino acids other than the said water absorbing amino acid or its salt, or its salt, According to the objective, it can select suitably.
Specific examples of amino acids other than the water-absorbing amino acid include aspartic acid, alanine, tyrosine, glycine, serine, leucine, phenylalanine, methionine, valine, isoleucine, threonine, tryptophan, ornithine, citrulline and the like.
Examples of salts of amino acids other than the water-absorbing amino acids include salts with inorganic acids or organic acids such as hydrochlorides, sulfates and acetates, salts with bases such as sodium salts and potassium salts, and the like. Specifically, sodium aspartate and the like can be mentioned.
Amino acids other than the water-absorbing amino acids or salts thereof or salts thereof may be used alone or in combination of two or more.
There is no restriction | limiting in particular as content of the amino acid other than the water absorbing amino acid or its salt in the said granule, or its salt, According to the quantity contained when it is set as a tablet, it can select suitably.

-Vitamins-
Examples of the vitamins are not particularly limited and may be appropriately selected depending on the purpose, for example, vitamin A, vitamin C, vitamin _{B 1,} vitamin _{B 2,} vitamin _{B 6,} vitamin _{B 12,} niacin, pantothenic acid Folic acid, biotin, vitamin D, vitamin E, hesperidin, inositol and the like.
Specific examples of the vitamin A raw material include retinol, retinal, retinoic acid, and retinol acetate.
Specific examples of the raw material of vitamin C include ascorbic acid, sodium ascorbate, calcium ascorbate, potassium ascorbate, magnesium ascorbate, ascorbyl palmitate, ascorbic acid phosphate and the like.
Specific examples of the raw material the vitamin B _1, thiamine, thiamine nitrate, thiamine hydrochloride and the like.
Specific examples of the raw material for vitamin B ₂ include riboflavin, riboflavin butyrate, sodium riboflavin 5′-phosphate, and the like.
Specific examples of the raw material for vitamin B ₆ include pyridoxine, pyridoxal, pyridoxamine, pyridoxine hydrochloride, pyridoxal phosphate, and the like.
Specific examples of the vitamin B ₁₂ raw material include cobalamin, hydroxocobalamin, adenosylcobalamin, methylcobalamin, cyanocobalamin, sulfitocobalamin and the like.
Specific examples of the raw material of the niacin (sometimes referred to as “vitamin B ₃ ”) include nicotinic acid and nicotinic acid amide.
Specific examples of the raw material of pantothenic acid (sometimes referred to as “vitamin B ₅ ”) include pantothenic acid, calcium pantothenate, sodium pantothenate and the like.
Specific examples of the raw material of the folic acid (sometimes referred to as “vitamin B ₉ ”) include folic acid, calcium folate, calcium 5-methyltetrahydrofolate, 5-methyltetrahydrofolic acid, and the like.
Specific examples of the raw material of the biotin (sometimes referred to as “vitamin B ₇ ”) include biotin.
Specific examples of the raw material for vitamin D include ergocalciferol and cholecalciferol.
Specific examples of the raw material for vitamin E include α-tocopherol, dl-α-tocopherol acetate, d-α-tocopherol acetate, l-α-tocopherol acetate, tocopherol acetate, and the like.
The said vitamins may be used individually by 1 type, and may use 2 or more types together.
There is no restriction | limiting in particular as content of the vitamins in the said granule, According to the quantity contained when it is set as a tablet, it can select suitably.

-Mineral-
There is no restriction | limiting in particular as said mineral, According to the objective, it can select suitably, For example, calcium, magnesium, zinc, iron, manganese, copper, selenium, chromium, molybdenum etc. are mentioned.
Specific examples of the calcium raw material include shell calcium, coral calcium, dolomite and the like.
Specific examples of the magnesium raw material include magnesium oxide and dolomite.
Specific examples of the zinc raw material include zinc-containing yeast and zinc gluconate.
Specific examples of the raw material for iron include ferric ammonium citrate, ferric chloride, ferric citrate, ferric phosphate, ferrous pyrophosphate, ferric pyrophosphate, ferric sulfate , Ferrous ascorbate, ferrous carboxylate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric hydroxide, ferric oxide Iron etc. are mentioned.
Specific examples of the manganese raw material include manganese-containing yeast.
Specific examples of the copper raw material include copper-containing yeast and copper gluconate.
Specific examples of the selenium raw material include selenium-containing yeast.
Specific examples of the chromium raw material include chromium-containing yeast.
Specific examples of the molybdenum raw material include molybdenum-containing yeast.
The said mineral may be used individually by 1 type, and may use 2 or more types together.
There is no restriction | limiting in particular as content of the mineral in the said granule, According to the quantity contained when it is set as a tablet, it can select suitably.

The functional component, various polyphenols, lubricants, disintegrants, excipients, binders, fixing agents, colorants, pH adjusters, buffers, and antioxidants are not particularly limited, It can be appropriately selected depending on the case. These may be used individually by 1 type and may use 2 or more types together.
The contents of the functional component, various polyphenols, lubricants, disintegrants, excipients, binders, binders, colorants, pH adjusters, buffers, and antioxidants are as follows. As long as the effect is not impaired, there is no particular limitation, and it can be selected appropriately according to the purpose.
Specific examples of the functional component include coenzyme Q10, α-lipoic acid, L-carnitine, collagen, hyaluronic acid, elastin, turmeric, glucosamine, chondroitin and the like.
Specific examples of the lubricant include stearic acid, calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, talc, fine silicon dioxide, light anhydrous silicic acid, hydrous silicon dioxide, vegetable oil and fat, hydrogenated oil Etc.
Specific examples of the excipient include starch such as lactose, brewer's yeast, dextrin and corn starch.
Specific examples of the binder include dextrin; natural polysaccharide; crystalline cellulose; crystalline cellulose / light anhydrous silicic acid (crystalline cellulose having light anhydrous silicic acid attached); cellulose such as hydroxypropylcellulose and hydroxypropylmethylcellulose Derivatives; reduced maltose starch syrup; sugar alcohols such as xylitol, sorbitol, mannitol, maltitol; trehalose; disaccharides such as palatinose and isomalt; soy polysaccharides;
Specific examples of the colorant include titanium oxide and iron oxide.
Specific examples of the pH adjusting agent and the buffering agent include sodium citrate, sodium acetate, sodium phosphate and the like.

(Tablets and production method thereof)
The tablet of this invention contains at least 1 sort (s) selected from a water absorbing amino acid or its salt, and yeast extract, and a water absorption inhibitor, and also contains another component as needed.
There is no restriction | limiting in particular as a manufacturing method of the tablet of this invention, Although it can select suitably according to the objective, The manufacturing method of the tablet of this invention is preferable.
Hereinafter, the tablet of the present invention will be described together with the description of the method for producing the tablet of the present invention.

<Tablet production method>
The tablet production method of the present invention includes at least a mixing step, a granulation step, and a tableting step, and further includes other steps as necessary.

<< Mixing process >>
The mixing step is a step of mixing at least one selected from a water-absorbing amino acid or a salt thereof and yeast extract and a water absorption inhibitor, and if necessary, further mixing other components. Good. The mixing step in the tablet production method can be performed in the same manner as the mixing step in the granule production method of the present invention described above.

<< Granulation process >>
The granulation step is a step of granulating the mixture obtained in the mixing step, and can be performed in the same manner as the granulation step in the above-described granule production method of the present invention.

<< Tabletting process >>
The tableting step is a step of tableting the granule obtained in the granulation step. That is, it is a step of tableting the granule of the present invention.
As the pressure of the filling pressurization in the tableting step (tableting pressure) is not particularly limited, as appropriate may be ^{selected, 6kg / cm 2 ~20kg / cm} 2 are preferred according to the purpose, 12 kg / cm ^{2 to} 16 kg / cm ² is more preferable. If the pressure is less than 6 kg / cm ² , sufficient hardness may not be obtained and tablets may become brittle or sticking may occur. If the pressure exceeds 20 kg / cm ² , capping may occur. . On the other hand, when the pressure is in the more preferable range, it is advantageous in that a tablet with sufficient hardness can be obtained and tableting troubles can be suppressed, for example, occurrence of sticking and capping can be suppressed.

  As an apparatus used for the tableting, for example, a tableting machine (for example, HT-APSS type, HT-AP-MS type, HT-X-SS type, HT-X-MS type (above, Hata Iron Works Co., Ltd.). VIRGO, AQUAARIUS, LIBRA (manufactured by Kikusui Seisakusho Co., Ltd.)) and the like.

<< Other processes >>
There is no restriction | limiting in particular as said other process, unless the effect of this invention is impaired, According to the objective, it can select suitably, For example, a granulation process, a tablet coating | coated process, etc. are mentioned.

-Sizing process-
The granulation step is a step of regulating the granules after the granulation step to obtain a uniform particle size. This is advantageous in that the handleability is improved in the tableting step.
The method for adjusting the particle size is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a method using a sieve having a desired opening.

-Tablet coating process-
The tablet coating step is a step of coating the tablet obtained in the tableting step with a coating agent.
There is no restriction | limiting in particular as said coating agent, According to the objective, it can select suitably, For example, shellac, zein, cellulose derivatives (hydroxypropylcellulose, hydroxypropylmethylcellulose, etc.) etc. are mentioned.
There is no restriction | limiting in particular as the said coating method, A well-known method can be selected suitably. There is no restriction | limiting in particular as an apparatus used for the said coating | cover, According to the objective, it can select suitably, For example, a high coater, a high coater FZ, an aqua coater (above, Freund Sangyo Co., Ltd. product), a POWREC coater, a powder. REC COATER EVO, Doria Coater (manufactured by POWREC Co., Ltd.)

<Tablets>
The tablet of the present invention can be suitably produced by the above-described method for producing a tablet of the present invention.
Since the tablet of the present invention is produced using the granule of the present invention, the occurrence of sticking in the tableting process is suppressed and can be easily obtained in a short time.

  There is no restriction | limiting in particular as the mass of 1 tablet of the said tablet, Although it can select suitably according to the number etc. of the component to mix | blend, 150 mg-500 mg are preferable, and 200 mg-460 mg are more preferable. If the mass is less than 150 mg, the target number of grains per day may increase, and the dosage may be inferior or the handling of the tablet may be inferior. If the mass exceeds 500 mg, the tablet is too large to be ingested. Sometimes.

-Content of at least one selected from water-absorbing amino acids or salts thereof and yeast extracts-
There is no restriction | limiting in particular as content of the at least 1 sort (s) selected from the water-absorbing amino acid or its salt, and yeast extract in the said tablet, Although it can select suitably according to the objective, 0 per tablet. It is preferably contained in an amount of 01% by mass to 50% by mass, more preferably 0.05% by mass to 40% by mass, and particularly preferably 0.1% by mass to 30% by mass.

-Silicate content-
There is no restriction | limiting in particular as content of the silicate in the said tablet, Although it can select suitably according to the objective, It is preferable that 0.01 mass%-10 mass% are contained per tablet, and 0. More preferably, the content is from 05% by mass to 5.0% by mass, and particularly preferably from 0.1% by mass to 2.0% by mass.

-Mass ratio of at least one selected from water-absorbing amino acids or salts thereof and yeast extracts and silicate-
There is no restriction | limiting in particular as an amount of the silicate with respect to at least 1 sort (s) selected from the said water absorbing amino acid or its salt, and yeast extract, Although it can select suitably according to the objective, Mass ratio (silicic acid) Salt / water-absorbing amino acid or a salt thereof, and at least one selected from yeast extracts), preferably 0.01 to 10.0, more preferably 0.1 to 5.0, and 0.2 to 2. 0 is particularly preferred.

There is no restriction | limiting in particular as a shape of the said tablet, Although it can select suitably according to the objective, A round tablet, a triangular tablet, other irregular shaped tablets, etc. are mentioned.
There is no restriction | limiting in particular as an average diameter of the said tablet, Although it can select suitably according to the objective, 6 mm-18 mm are preferable and 7 mm-10 mm are more preferable at the point of the ease of taking.
There is no restriction | limiting in particular as thickness of the said tablet, Although it can select suitably according to the objective, 2 mm-7 mm are preferable at the point of the ease of taking, and 3 mm-6 mm are more preferable.

In the tablet, the granule may be coated or uncoated, but it is preferable that the granule is not coated in that the tablet can be produced easily and in a short time.
The tablet may or may not be sugar-coated on the tablet, but is preferably not sugar-coated in that it can be produced easily and in a short time. .

<< Other ingredients >>
The other components in the tablet are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. Other components similar to the other components of the granule of the present invention described above. Can be included.
The tablet of the present invention comprises, in addition to at least one selected from the water-absorbing amino acids or salts thereof, and yeast extracts, and at least one amino acid other than at least one water-absorbing amino acid or salts thereof, or salts thereof. Preferably it contains seed vitamins and at least one mineral.
There is no restriction | limiting in particular as content of the amino acid or its salt other than the water absorbing amino acid or its salt in the said tablet, Although it can select suitably according to the objective, 0.01 mass%-50 mass per tablet %, Preferably 0.05% to 40% by weight, more preferably 0.1% to 30% by weight.
There is no restriction | limiting in particular as content of vitamins in the said tablet, Although it can select suitably according to the objective, It is preferable that 0.01 mass%-50 mass% are contained per tablet, 0.05 More preferably, it is contained by mass% to 45 mass%, particularly preferably 0.1 mass% to 40 mass%.
There is no restriction | limiting in particular as content of the mineral in the said tablet, Although it can select suitably according to the objective, It is preferable that 0.01 mass%-50 mass% are contained per tablet, 0.05 mass % To 45% by mass is more preferable, and 0.1% to 40% by mass is particularly preferable.

  EXAMPLES The present invention will be specifically described below with reference to examples of the present invention, but the present invention is not limited to these examples.

(Test Example 1: Production of granules and tablets)
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used, and the mixture was mixed under the following mixing conditions so that the following composition and blending amount (per mixture) were obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ Histidine 8.67% by mass
(L-histidine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Arginine-glutamate 22.61% by mass
(L-arginine L-glutamate, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Sodium aspartate 7.84% by mass
(L-sodium aspartate, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Alanine 19.06 mass%
(DL-alanine, Ajinomoto Healthy Supply Co., Ltd.)
・ Cystine 1.55% by mass
(L-cystine (CF-3), manufactured by Nippon Rika Chemical Co., Ltd.)
・ Proline 5.05 mass%
(L-proline, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tyrosine 0.54% by mass
(L-tyrosine, manufactured by Nippon Rika Chemical Co., Ltd.)
・ Glycine 16.37 mass%
(Glycine P, Organic Synthetic Chemical Industry Co., Ltd.)
・ Serine 3.37% by mass
(L-serine, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Reduced palatinose 14.94% by mass
(Powder reduced palatinose PNP, Mitsui Sugar Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
The mixture is put in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.) and granulated while uniformly spraying the granulating spray solution under the following granulation conditions. Granules were prepared. The median diameter (d50) of the granules was measured by a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and was 250 μm.
In the granulation step, since the water-absorbing amino acid was contained in the mixture, it was confirmed that blocking occurred midway (see FIG. 1).
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ Histidine 8.54% by mass
-Arginine-glutamate 22.27% by mass
・ Sodium aspartate 7.72% by mass
・ Alanine 18.77 mass%
・ Cystine 1.53 mass%
・ Proline 4.98% by mass
・ Tyrosine 0.53 mass%
・ Glycine 16.12% by mass
・ Serine 3.32 mass%
・ Reduced palatinose 14.72% by mass
・ Pullulan 1.50% by mass
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature Round tablets with a radius (R) of 7.5 mm and 440 mg / tablet were obtained. In the tableting process, sticking occurred in the middle (see FIG. 2), and the production efficiency was low. In FIG. 2, left and right indicate a state where sticking is strongly generated, and a center indicates a state where sticking occurs and the heel surface is cloudy.
[Composition of tableting powder]
・ The granulated granules 22.61% by mass
・ Lysine hydrochloride 3.46% by mass
(L-lysine hydrochloride, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Leucine 3.30% by mass
(L-leucine, Ajinomoto Healthy Supply Co., Ltd.)
・ Phenylalanine 3.26% by mass
(L-phenylalanine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Methionine 3.24% by mass
(L-methionine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Valine 2.36% by mass
(L-Valine, Ajinomoto Healthy Supply Co., Ltd.)
・ Isoleucine 2.33% by mass
(L-isoleucine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Threonine 1.63 mass%
(L-threonine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tryptophan 0.94 mass%
(L-tryptophan, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Vitamin A 0.47% by mass
(Dry vitamin A acetate 326,000 IU / g, manufactured by BASF Japan Ltd.)
・ Vitamin C 6.31% by mass
(Vitamin C granule-97, manufactured by BASF Japan Ltd.)
・ Vitamin B ₂ 0.90% by mass
(Vitamin B ₂ (riboflavin FP), manufactured by BASF Japan Ltd.)
・ Vitamin B ₁₂ 0.26% by mass
_(VB 12 · 1000 triturated, manufactured by Organo Co., Ltd.)
・ Calcium pantothenate 0.56% by mass
(Calcium pantothenate, manufactured by Daiichi Fine Chemical Co., Ltd.)
・ Vitamin D 0.08% by mass
(Dry vitamin D3, manufactured by Mitsubishi Chemical Foods Corporation)
・ Vitamin E acetate 1.33% by mass
(Tocopherol acetate 50% powder, manufactured by BASF Japan Ltd.)
・ Shellfish calcium 19.94 mass%
(Uncalcined calcium (scallop powder), manufactured by NC Corporation)
・ Dextrin 3.99% by mass
(Paindex (registered trademark) # 100, manufactured by Matsutani Chemical Co., Ltd.)
・ Magnesium oxide 6.58 mass%
(Magnesium oxide heavy (fine grain) STS, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Zinc gluconate 4.26 mass%
(Zinc gluconate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Iron pyrophosphate 0.96% by mass
(Zinc gluconate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Cellulose 10.23 mass%
(Theolas UF-F711, manufactured by Asahi Kasei Chemicals Corporation)
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Test Example 1 are as follows.
[Blending amount (blending rate)]
-Histidine 8.49 mg (1.93 mass%)
Arginine-glutamate 22.18 mg (5.04% by mass)
・ Sodium aspartate 7.70 mg (1.75 mass%)
・ Alanine 18.70 mg (4.25 mass%)
-Cystine 1.50 mg (0.34% by mass)
・ Proline 4.97mg (1.13 mass%)
・ Tyrosine 0.53mg (0.12% by mass)
・ Glycine 16.06mg (3.65% by mass)
・ Serine 3.30mg (0.75 mass%)
・ Lysine hydrochloride 15.22mg (3.46% by mass)
・ Leucine 14.52mg (3.30% by mass)
・ Phenylalanine 14.34 mg (3.26% by mass)
・ Methionine 14.26 mg (3.24 mass%)
・ Valine 10.38mg (2.36% by mass)
・ Isoleucine 10.25mg (2.33 mass%)
・ Threonine 7.17mg (1.63 mass%)
・ Tryptophan 4.14mg (0.94% by mass)
・ Vitamin A 2.07mg (0.47% by mass)
・ Vitamin C 27.76mg (6.31% by mass)
・ Vitamin B ₂ 3.96mg (0.90 mass%)
・ Vitamin B ₁₂ 1.14mg (0.26% by mass)
・ Calcium pantothenate 2.46mg (0.56% by mass)
・ Vitamin D 0.35mg (0.08 mass%)
・ Vitamin E acetate 5.85mg (1.33 mass%)
・ Shellfish calcium 87.74mg (19.94% by mass)
・ Dextrin 17.56 mg (3.98 mass%)
・ Magnesium oxide 28.95mg (6.58% by mass)
・ Zinc gluconate 18.74mg (4.26% by mass)
・ Iron pyrophosphate 4.22mg (0.96% by mass)
・ Pullulan 1.50mg (0.34 mass%)
-Reduced palatinose 14.60 mg (3.32% by mass)
・ Cellulose 44.99 mg (10.23 mass%)
・Calcium stearate 4.40mg (1.00% by mass)
Total 440.00mg (100.00% by mass)

(Test Example 2: Production of granules and tablets)
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used, and the mixture was mixed under the following mixing conditions so that the following composition and blending amount (per mixture) were obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ Lysine hydrochloride 3.91% by mass
(L-lysine hydrochloride, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Leucine 3.73 mass%
(L-leucine, Ajinomoto Healthy Supply Co., Ltd.)
・ Phenylalanine 3.69 mass%
(L-phenylalanine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Methionine 3.66% by mass
(L-methionine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Valine 2.67% by mass
(L-Valine, Ajinomoto Healthy Supply Co., Ltd.)
・ Isoleucine 2.63 mass%
(L-isoleucine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Threonine 1.84% by mass
(L-threonine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tryptophan 1.06% by mass
(L-tryptophan, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Histidine 2.18% by mass
(L-histidine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
Arginine-glutamate 5.69% by mass
(L-arginine L-glutamate, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Sodium aspartate 1.97 mass%
(L-sodium aspartate, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Alanine 4.80% by mass
(DL-alanine, Ajinomoto Healthy Supply Co., Ltd.)
・ Cystine 0.39% by mass
(L-cystine (CF-3), manufactured by Nippon Rika Chemical Co., Ltd.)
・ Proline 1.27 mass%
(L-proline, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tyrosine 0.14% by mass
(L-tyrosine, manufactured by Nippon Rika Chemical Co., Ltd.)
・ Glycine 4.12% by mass
(Glycine P, Organic Synthetic Chemical Industry Co., Ltd.)
・ Serine 0.85 mass%
(L-serine, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Vitamin A 0.53 mass%
(Dry vitamin A acetate 326,000 IU / g, manufactured by BASF Japan Ltd.)
・ Vitamin C 7.14% by mass
(Vitamin C granule-97, manufactured by BASF Japan Ltd.)
・ Vitamin B ₂ 1.02% by mass
(Vitamin B ₂ (riboflavin FP), manufactured by BASF Japan Ltd.)
・ Vitamin B ₁₂ 0.29% by mass
_(VB 12 · 1000 triturated, manufactured by Organo Co., Ltd.)
・ Calcium pantothenate 0.63 mass%
(Calcium pantothenate, manufactured by Daiichi Fine Chemical Co., Ltd.)
・ Vitamin D 0.09% by mass
(Dry vitamin D3, manufactured by Mitsubishi Chemical Foods Corporation)
・ Vitamin E acetate 1.50% by mass
(Tocopherol acetate 50% powder, manufactured by BASF Japan Ltd.)
・ Shellfish calcium 22.55% by mass
(Uncalcined calcium (scallop powder), manufactured by NC Corporation)
・ Dextrin 4.51% by mass
(Paindex (registered trademark) # 100, manufactured by Matsutani Chemical Co., Ltd.)
・ Magnesium oxide 7.44% by mass
(Magnesium oxide heavy (fine grain) STS, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Zinc gluconate 4.82 mass%
(Zinc gluconate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Iron pyrophosphate 1.09 mass%
(Ferric pyrophosphate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Reduced palatinose 3.79% by mass
(Powder reduced palatinose PNP, Mitsui Sugar Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
The mixture is put in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.) and granulated while uniformly spraying the granulating spray solution under the following granulation conditions. Granules were prepared. The median diameter (d50) of the granules was measured with a laser diffraction / scattering particle diameter / particle size distribution measuring device Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and found to be 350 μm.
In the granulation step, since the water-absorbing amino acid was contained in the mixture, it was confirmed that blocking occurred in the middle as in Test Example 1.
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ Lysine hydrochloride 3.90% by mass
・ Leucine 3.72 mass%
・ Phenylalanine 3.67% by mass
・ Methionine 3.65% by mass
・ 2.66% by mass of valine
・ Isoleucine 2.62% by mass
・ Threonine 1.84% by mass
・ Tryptophan 1.06% by mass
・ Histidine 2.17% by mass
-Arginine-glutamate 5.67% by mass
・ Sodium aspartate 1.97 mass%
・ Alanine 4.78% by mass
・ Cystine 0.39% by mass
・ Proline 1.27 mass%
・ Tyrosine 0.14% by mass
・ Glycine 4.11% by mass
・ Serine 0.84 mass%
・ Vitamin A 0.53 mass%
・ Vitamin C 7.11% by mass
・ Vitamin B ₂ 1.01% by mass
・ Vitamin B ₁₂ 0.29% by mass
・ Calcium pantothenate 0.63 mass%
・ Vitamin D 0.09% by mass
・ Vitamin E acetate 1.50% by mass
・ Shellfish calcium 22.46% by mass
・ Dextrin 4.49% by mass
・ Magnesium oxide 7.41% by mass
・ Zinc gluconate 4.80 mass%
・ Iron pyrophosphate 1.08% by mass
・ Pullulan 0.38 mass%
・ Reduced palatinose 3.76% by mass
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature Round tablets with a radius (R) of 7.5 mm and 440 mg / tablet were obtained.
In the tableting step, it was confirmed that sticking occurred midway as in Test Example 1.
[Composition of tableting powder]
-The granulated granules 88.78% by mass
・ Cellulose 10.22 mass%
(Theolas UF-F711, manufactured by Asahi Kasei Chemicals Corporation)
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Test Example 2 are as follows.
[Blending amount (blending rate)]
-Histidine 8.49 mg (1.93 mass%)
Arginine-glutamate 22.18 mg (5.04% by mass)
・ Sodium aspartate 7.70 mg (1.75 mass%)
・ Alanine 18.70 mg (4.25 mass%)
-Cystine 1.50 mg (0.34% by mass)
・ Proline 4.97mg (1.13 mass%)
・ Tyrosine 0.53mg (0.12% by mass)
・ Glycine 16.06mg (3.65% by mass)
・ Serine 3.30mg (0.75 mass%)
・ Lysine hydrochloride 15.22mg (3.46% by mass)
・ Leucine 14.52mg (3.30% by mass)
・ Phenylalanine 14.34 mg (3.26% by mass)
・ Methionine 14.26 mg (3.24 mass%)
・ Valine 10.38mg (2.36% by mass)
・ Isoleucine 10.25mg (2.33 mass%)
・ Threonine 7.17mg (1.63 mass%)
・ Tryptophan 4.14mg (0.94% by mass)
・ Vitamin A 2.07mg (0.47% by mass)
・ Vitamin C 27.76mg (6.31% by mass)
・ Vitamin B ₂ 3.96mg (0.90 mass%)
・ Vitamin B ₁₂ 1.14mg (0.26% by mass)
・ Calcium pantothenate 2.46mg (0.56% by mass)
・ Vitamin D 0.35mg (0.08 mass%)
・ Vitamin E acetate 5.85mg (1.33 mass%)
・ Shellfish calcium 87.74mg (19.94% by mass)
・ Dextrin 17.56 mg (3.98 mass%)
・ Magnesium oxide 28.95mg (6.58% by mass)
・ Zinc gluconate 18.74mg (4.26% by mass)
・ Iron pyrophosphate 4.22mg (0.96% by mass)
・ Pullulan 1.50mg (0.34 mass%)
-Reduced palatinose 14.60 mg (3.32% by mass)
・ Cellulose 44.99 mg (10.23 mass%)
・ Calcium stearate 4.40mg (1.00% by mass)
Total 440.00mg (100.00% by mass)

(Test Example 3: Production of granules and tablets)
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used, and the mixture was mixed under the following mixing conditions so that the following composition and blending amount (per mixture) were obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ VB1-containing yeast extract 40.82% by mass
(Mist P5 Thiamine Asahi Food and Healthcare)
・ Peptide-containing yeast extract 20.41% by mass
(Springer HYP A Bio Springer)
・ Cysteine peptide-containing yeast extract 12.24% by mass
(Hythion extract YH-15 manufactured by Kojinsha Co., Ltd.)
・ Dextrin 26.53 mass%
(Paindex # 100 Made by Matsutani Chemical Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
After weighing the composition, it was passed through a sieve having an opening of 850 μm, and then placed in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.). Granulation was carried out while uniformly spraying under granule conditions to prepare granules. The median diameter (d50) of the granules was measured by a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and was 250 μm.
In the granulation step, it was confirmed that blocking occurred during the granulation because the mixture contained yeast extract.
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ VB1-containing yeast extract 40.40% by mass
・ Peptide-containing yeast extract 20.20%
・ Cysteine peptide-containing yeast extract 12.12% by mass
・ Dextrin 26.26 mass%
・ Pullulan 1.02% by mass
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature A round tablet with a radius (R) of 7.5 mm and 250 mg / tablet was obtained.
In the tableting process, it was confirmed that sticking occurred during tableting.
[Composition of tableting powder]
・ The granulated granule 99.00% by mass
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Test Example 3 are as follows.
[Blending amount (blending rate)]
・ VB1-containing yeast extract 100.00mg (40.00% by mass)
・ Peptide-containing yeast extract 50.00mg (20.00% by mass)
・ Cysteine peptide-containing yeast extract 30.00 mg (12.00% by mass)
・ Dextrin 64.95mg (25.98% by mass)
・ Pullulan 2.55mg (1.02% by mass)
・ Calcium stearate 2.50mg (1.00% by mass)
(Lubricant, Sakai Chemical Industry Co., Ltd.)
Total 250.00mg (100.00% by mass)

Example 1
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used to obtain a mixture having the following composition and blending amount (per mixture).
In addition, the said mixing process was performed as follows.

-Mixing (1)-
Arginine-glutamate, proline and calcium silicate were weighed, passed through a sieve having an aperture of 850 mm, and then mixed under the following mixing conditions to obtain a mixture (1).
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

-Mixing (2)-
To the mixture (1), after weighing, sodium aspartate, serine, histidine, alanine, cystine, tyrosine, glycine, and reduced palatinose that have been sieved with an opening of 850 mm are added and mixed under the following mixing conditions. 2) was obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ Histidine 8.67% by mass
(L-histidine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Arginine-glutamate 22.61% by mass
(L-arginine L-glutamate, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Sodium aspartate 7.84% by mass
(L-sodium aspartate, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Alanine 19.06 mass%
(DL-alanine, Ajinomoto Healthy Supply Co., Ltd.)
・ Cystine 1.55% by mass
(L-cystine (CF-3), manufactured by Nippon Rika Chemical Co., Ltd.)
・ Proline 5.05 mass%
(L-proline, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tyrosine 0.54% by mass
(L-tyrosine, manufactured by Nippon Rika Chemical Co., Ltd.)
・ Glycine 16.37 mass%
(Glycine P, Organic Synthetic Chemical Industry Co., Ltd.)
・ Serine 3.37% by mass
(L-serine, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Calcium silicate 8.98% by mass
(Florite R Tomita Pharmaceutical Co., Ltd.)
・ Reduced palatinose 5.96% by mass
(Powder reduced palatinose PNP, Mitsui Sugar Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
The mixture is put in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.) and granulated while uniformly spraying the granulating spray solution under the following granulation conditions. Granules were prepared. The median diameter (d50) of the granule 1-1 was measured by a laser diffraction / scattering particle diameter / particle size distribution measuring device Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and it was 280 μm.
In Example 1, since calcium silicate was mixed with at least one water-absorbing amino acid in the mixing step as a water absorption inhibitor, the mixture was not fixed during granulation, and blocking occurred. I was able to suppress it.
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ Histidine 8.54% by mass
-Arginine-glutamate 22.27% by mass
・ Sodium aspartate 7.72% by mass
・ Alanine 18.77 mass%
・ Cystine 1.53 mass%
・ Proline 4.98% by mass
・ Tyrosine 0.53 mass%
・ Glycine 16.12% by mass
・ Serine 3.32 mass%
・ Calcium silicate 8.85 mass%
・ Reduced palatinose 5.87% by mass
・ Pullulan 1.50% by mass
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature Round tablets with a radius (R) of 7.5 mm and 440 mg / tablet were obtained.
In Example 1, since the granule was produced by mixing calcium silicate as a water absorption inhibitor with at least one water-absorbing amino acid in the mixing step, the granule draws water in the tableting step. It was possible to suppress the occurrence of sticking.
[Composition of tableting powder]
・ The granulated granules 22.61% by mass
・ Lysine hydrochloride 3.46% by mass
(L-lysine hydrochloride, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Leucine 3.30% by mass
(L-leucine, Ajinomoto Healthy Supply Co., Ltd.)
・ Phenylalanine 3.26% by mass
(L-phenylalanine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Methionine 3.24% by mass
(L-methionine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Valine 2.36% by mass
(L-Valine, Ajinomoto Healthy Supply Co., Ltd.)
・ Isoleucine 2.33% by mass
(L-isoleucine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Threonine 1.63 mass%
(L-threonine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tryptophan 0.94 mass%
(L-tryptophan, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Vitamin A 0.47% by mass
(Dry vitamin A acetate 326,000 IU / g, manufactured by BASF Japan Ltd.)
・ Vitamin C 6.31% by mass
(Vitamin C granule-97, manufactured by BASF Japan Ltd.)
・ Vitamin B ₂ 0.90% by mass
(Vitamin B ₂ (riboflavin FP), manufactured by BASF Japan Ltd.)
・ Vitamin B ₁₂ 0.26% by mass
_(VB 12 · 1000 triturated, manufactured by Organo Co., Ltd.)
・ Calcium pantothenate 0.56% by mass
(Calcium pantothenate, manufactured by Daiichi Fine Chemical Co., Ltd.)
・ Vitamin D 0.08% by mass
(Dry vitamin D3, manufactured by Mitsubishi Chemical Foods Corporation)
・ Vitamin E acetate 1.33% by mass
(Tocopherol acetate 50% powder, manufactured by BASF Japan Ltd.)
・ Shellfish calcium 19.94 mass%
(Uncalcined calcium (scallop powder), manufactured by NC Corporation)
・ Dextrin 3.99% by mass
(Paindex (registered trademark) # 100, manufactured by Matsutani Chemical Co., Ltd.)
・ Magnesium oxide 6.58 mass%
(Magnesium oxide heavy (fine grain) STS, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Zinc gluconate 4.26 mass%
(Zinc gluconate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Iron pyrophosphate 0.96% by mass
(Ferric pyrophosphate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Cellulose 10.23 mass%
(Theolas UF-F711, manufactured by Asahi Kasei Chemicals Corporation)
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Example 1 are as follows.
[Blending amount (blending rate)]
-Histidine 8.49 mg (1.93 mass%)
Arginine-glutamate 22.18 mg (5.04% by mass)
・ Sodium aspartate 7.70 mg (1.75 mass%)
・ Alanine 18.70 mg (4.25 mass%)
-Cystine 1.50 mg (0.34% by mass)
・ Proline 4.97mg (1.13 mass%)
・ Tyrosine 0.53mg (0.12% by mass)
・ Glycine 16.06mg (3.65% by mass)
・ Serine 3.30mg (0.75 mass%)
・ Lysine hydrochloride 15.22mg (3.46% by mass)
・ Leucine 14.52mg (3.30% by mass)
・ Phenylalanine 14.34 mg (3.26% by mass)
・ Methionine 14.26 mg (3.24 mass%)
・ Valine 10.38mg (2.36% by mass)
・ Isoleucine 10.25mg (2.33 mass%)
・ Threonine 7.17mg (1.63 mass%)
・ Tryptophan 4.14mg (0.94% by mass)
・ Vitamin A 2.07mg (0.47% by mass)
・ Vitamin C 27.76mg (6.31% by mass)
・ Vitamin B ₂ 3.96mg (0.90 mass%)
・ Vitamin B ₁₂ 1.14mg (0.26% by mass)
・ Calcium pantothenate 2.46mg (0.56% by mass)
・ Vitamin D 0.35mg (0.08 mass%)
・ Vitamin E acetate 5.85mg (1.33 mass%)
・ Shellfish calcium 87.74mg (19.94% by mass)
・ Dextrin 17.56 mg (3.98 mass%)
・ Magnesium oxide 28.95mg (6.58% by mass)
・ Zinc gluconate 18.74mg (4.26% by mass)
・ Iron pyrophosphate 4.22mg (0.96% by mass)
・ Pullulan 1.50mg (0.34 mass%)
-Reduced palatinose 5.81 mg (1.32% by mass)
・ Calcium silicate 8.80mg (2.00% by mass)
・ Cellulose 44.98 mg (10.23 mass%)
・ Calcium stearate 4.40mg (1.00% by mass)
Total 440.00mg (100.00% by mass)

(Example 2)
In the mixing step of Example 1, the amount of calcium silicate (FLORITE R, manufactured by Tomita Pharmaceutical Co., Ltd.) was changed from 8.98% by mass to 4.43% by mass, and the amount of reduced palatinose used was 5.96. A tablet was produced in the same manner as in Example 1 except that the content was changed from 10% by mass to 10.34% by mass.
In Example 2, as in Example 1, calcium silicate as a water absorption inhibitor was mixed with at least one water-absorbing amino acid in the mixing step, so that the mixture was fixed during granulation. In the tableting process, it was possible to prevent the granules from drawing moisture, and to suppress the occurrence of sticking.
The blending amount and blending ratio of each component per tablet of Example 2 were 4.40 mg (1.00% by mass) for calcium silicate and 10.21 mg (2.31% by mass) for reduced palatinose. Except that, it is the same as Example 1.

(Example 3: Production of granules and tablets)
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used, and the mixture was mixed under the following mixing conditions so that the following composition and blending amount (per mixture) were obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ Lysine hydrochloride 3.91% by mass
(L-lysine hydrochloride, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Leucine 3.73 mass%
(L-leucine, Ajinomoto Healthy Supply Co., Ltd.)
・ Phenylalanine 3.69 mass%
(L-phenylalanine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Methionine 3.66% by mass
(L-methionine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Valine 2.67% by mass
(L-Valine, Ajinomoto Healthy Supply Co., Ltd.)
・ Isoleucine 2.63 mass%
(L-isoleucine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Threonine 1.84% by mass
(L-threonine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tryptophan 1.06% by mass
(L-tryptophan, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Histidine 2.18% by mass
(L-histidine, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
Arginine-glutamate 5.69% by mass
(L-arginine L-glutamate, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Sodium aspartate 1.97 mass%
(L-sodium aspartate, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Alanine 4.80% by mass
(DL-alanine, Ajinomoto Healthy Supply Co., Ltd.)
・ Cystine 0.39% by mass
(L-cystine (CF-3), manufactured by Nippon Rika Chemical Co., Ltd.)
・ Proline 1.27 mass%
(L-proline, manufactured by Ajinomoto Healthy Supply Co., Ltd.)
・ Tyrosine 0.14% by mass
(L-tyrosine, manufactured by Nippon Rika Chemical Co., Ltd.)
・ Glycine 4.12% by mass
(Glycine P, Organic Synthetic Chemical Industry Co., Ltd.)
・ Serine 0.85 mass%
(L-serine, manufactured by Kyowa Hakko Bio Co., Ltd.)
・ Vitamin A 0.53 mass%
(Dry vitamin A acetate 326,000 IU / g, manufactured by BASF Japan Ltd.)
・ Vitamin C 7.14% by mass
(Vitamin C granule-97, manufactured by BASF Japan Ltd.)
・ Vitamin B ₂ 1.02% by mass
(Vitamin B ₂ (riboflavin FP), manufactured by BASF Japan Ltd.)
・ Vitamin B ₁₂ 0.29% by mass
_(VB 12 · 1000 triturated, manufactured by Organo Co., Ltd.)
・ Calcium pantothenate 0.63 mass%
(Calcium pantothenate, manufactured by Daiichi Fine Chemical Co., Ltd.)
・ Vitamin D 0.09% by mass
(Dry vitamin D3, manufactured by Mitsubishi Chemical Foods Corporation)
・ Vitamin E acetate 1.50% by mass
(Tocopherol acetate 50% powder, manufactured by BASF Japan Ltd.)
・ Shellfish calcium 22.55% by mass
(Uncalcined calcium (scallop powder), manufactured by NC Corporation)
・ Dextrin 4.51% by mass
(Paindex (registered trademark) # 100, manufactured by Matsutani Chemical Co., Ltd.)
・ Magnesium oxide 7.44% by mass
(Magnesium oxide heavy (fine grain) STS, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Zinc gluconate 4.82 mass%
(Zinc gluconate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Iron pyrophosphate 1.09 mass%
(Ferric pyrophosphate, manufactured by Tomita Pharmaceutical Co., Ltd.)
・ Calcium silicate 2.25% by mass
(Florite R Tomita Pharmaceutical Co., Ltd.)
・ Reduced palatinose 1.54% by mass
(Powder reduced palatinose PNP, Mitsui Sugar Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
The mixture is put in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.) and granulated while uniformly spraying the granulating spray solution under the following granulation conditions. Granules were prepared. The median diameter (d50) of the granules was measured with a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and found to be 365 μm.
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ Lysine hydrochloride 3.90% by mass
・ Leucine 3.72 mass%
・ Phenylalanine 3.67% by mass
・ Methionine 3.65% by mass
・ 2.66% by mass of valine
・ Isoleucine 2.62% by mass
・ Threonine 1.84% by mass
・ Tryptophan 1.06% by mass
・ Histidine 2.17% by mass
-Arginine-glutamate 5.67% by mass
・ Sodium aspartate 1.97 mass%
・ Alanine 4.78% by mass
・ Cystine 0.39% by mass
・ Proline 1.27 mass%
・ Tyrosine 0.14% by mass
・ Glycine 4.11% by mass
・ Serine 0.84 mass%
・ Vitamin A 0.53 mass%
・ Vitamin C 7.11% by mass
・ Vitamin B ₂ 1.01% by mass
・ Vitamin B ₁₂ 0.29% by mass
・ Calcium pantothenate 0.63 mass%
・ Vitamin D 0.09% by mass
・ Vitamin E acetate 1.50% by mass
・ Shellfish calcium 22.45% by mass
・ Dextrin 4.49% by mass
・ Magnesium oxide 7.41% by mass
・ Zinc gluconate 4.80 mass%
・ Iron pyrophosphate 1.08% by mass
・ Pullulan 0.38 mass%
・ Calcium silicate 2.24% by mass
・ Reduced palatinose 1.53 mass%
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature Round tablets with a radius (R) of 7.5 mm and 440 mg / tablet were obtained.
In Example 3 as well, as in Example 1, calcium silicate as a water absorption inhibitor was mixed with at least one water-absorbing amino acid in the mixing step, so that the mixture was fixed during granulation. In the tableting process, it was possible to prevent the granules from drawing moisture, and to suppress the occurrence of sticking.
[Composition of tableting powder]
-The granulated granules 88.78% by mass
・ Cellulose 10.22 mass%
(Theolas UF-F711, manufactured by Asahi Kasei Chemicals Corporation)
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Example 3 are as follows.
[Blending amount (blending rate)]
・ Lysine hydrochloride 15.23mg (3.46% by mass)
-Leucine 14.53 mg (3.30 mass%)
・ Phenylalanine 14.34 mg (3.26% by mass)
・ Methionine 14.26 mg (3.24 mass%)
・ Valine 10.39mg (2.36% by mass)
・ Isoleucine 10.23 mg (2.33 mass%)
・ Threonine 7.19mg (1.63 mass%)
・ Tryptophan 4.14mg (0.94% by mass)
-Histidine 8.48 mg (1.93 mass%)
Arginine-glutamate 22.15 mg (5.03% by mass)
・ Sodium aspartate 7.70 mg (1.75 mass%)
・ Alanine 18.67 mg (4.24 mass%)
・ Cystine 1.52mg (0.35 mass%)
・ Proline 4.96 mg (1.13 mass%)
・ Tyrosine 0.55mg (0.12% by mass)
・ Glycine 16.05mg (3.65% by mass)
・ Serine 3.28 mg (0.75 mass%)
・ Vitamin A 2.07mg (0.47% by mass)
・ Vitamin C 27.77mg (6.31% by mass)
・ Vitamin B ₂ 3.95mg (0.90 mass%)
・ Vitamin B ₁₂ 1.13mg (0.26% by mass)
・ Calcium pantothenate 2.46mg (0.56% by mass)
・ Vitamin D 0.35mg (0.08 mass%)
・ Vitamin E acetate 5.86mg (1.33 mass%)
・ Shellfish calcium 87.74mg (19.94% by mass)
・ Dextrin 17.54 mg (3.98 mass%)
・ Magnesium oxide 28.95mg (6.58% by mass)
・ Zinc gluconate 18.75mg (4.26% by mass)
・ Iron pyrophosphate 4.22mg (0.96% by mass)
・ Pullulan 1.48mg (0.34 mass%)
・ Calcium silicate 8.75mg (1.99% by mass)
-Reduced palatinose 5.96 mg (1.35% by mass)
・ Cellulose 44.95mg (10.22% by mass)
・ Calcium stearate 4.40mg (1.00% by mass)
Total 440.00mg (100.00% by mass)

Example 4
<Mixing process>
As a mixing device, a Boule container mixer (manufactured by Kotobuki Industries Co., Ltd.) was used, and the mixture was mixed under the following mixing conditions so that the following composition and blending amount (per mixture) were obtained.
[Mixing conditions]
・ Temperature: 25 ℃
・ Time: 5 minutes

〔composition〕
・ VB1-containing yeast extract 40.82% by mass
(Mist P5 Thiamine Asahi Food and Healthcare)
・ Peptide-containing yeast extract 20.41% by mass
(Springer HYP A Bio Springer)
・ Cysteine peptide-containing yeast extract 12.24% by mass
(Hythion extract YH-15 manufactured by Kojinsha Co., Ltd.)
・ Dextrin 24.49 mass%
(Paindex # 100 Made by Matsutani Chemical Co., Ltd.)
・ Calcium silicate 2.04% by mass
(Florite R Tomita Pharmaceutical Co., Ltd.)
Total 100.00% by mass

<Granulation process>
-Preparation of spray solution for granulation-
An aqueous solution containing 6.0% by mass of pullulan (manufactured by Hayashibara Shoji Co., Ltd.) was prepared as a granulating spray.

-Granulation-
After weighing the composition, it was passed through a sieve having an opening of 850 μm, and then placed in a fluidized bed granulator (rolling fluidized coating device-MP-01, manufactured by POWREC Co., Ltd.). Granulation was carried out while uniformly spraying under granule conditions to prepare granules. The median diameter (d50) of the granules was measured by a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.), and was 250 μm.
In the granulation step, it was confirmed that blocking occurred during the granulation because the mixture contained yeast extract.
[Granulation conditions]
・ Supply air temperature: 70 ℃
・ Exhaust temperature: 35 ℃
・ Spraying speed: 5 mL / min ・ Total spraying time: 30 minutes

The composition of each component in the granule is as follows.
〔composition〕
・ VB1-containing yeast extract 40.40% by mass
・ Peptide-containing yeast extract 20.20%
・ Cysteine peptide-containing yeast extract 12.12% by mass
・ Dextrin 24.25 mass%
・ Calcium silicate 2.02% by mass
・ Pullulan 1.01% by mass
Total 100.00% by mass

<Drying process, sizing process>
The granules were dried at 90 ° C. until the water content was 2% by mass or less, and sized using a sieve having an opening of 1.00 mm.

<Tabletting process>
Using a tableting machine (HT-AP12SS-U, manufactured by Hata Iron Works Co., Ltd.), a tableting powder having the following composition was filled and pressed at a pressure of 15 kg / cm ² by a conventional method, and tableting was performed. Diameter 9 mm, curvature A round tablet with a radius (R) of 7.5 mm and 250 mg / tablet was obtained.
In Example 4, as in Example 1, calcium silicate as a water absorption inhibitor was mixed with at least one yeast extract in the mixing step. Therefore, it was possible to suppress the occurrence of blocking, and it was possible to suppress the granule from drawing moisture in the tableting process, and to suppress the occurrence of sticking.
[Composition of tableting powder]
・ The granulated granule 99.00% by mass
・ Calcium stearate (lubricant, manufactured by Sakai Chemical Industry Co., Ltd.) 1.00% by mass
Total 100.00% by mass

The blending amount and blending ratio of each component per tablet of Example 4 are as follows.
[Blending amount (blending rate)]
・ VB1-containing yeast extract 100.00mg (40.00% by mass)
・ Peptide-containing yeast extract 50.00mg (20.00% by mass)
・ Cysteine peptide-containing yeast extract 30.00 mg (12.00% by mass)
・ Dextrin 60.00mg (24.00% by mass)
・ Calcium silicate 5.00mg (2.00% by mass)
・ Pullulan 2.50mg (1.00% by mass)
・ Calcium stearate 2.50mg (1.00% by mass)
(Lubricant, Sakai Chemical Industry Co., Ltd.)
Total 250.00mg (100.00% by mass)

According to the method for producing a granule of the present invention, it is possible to suppress blocking in the granulating step despite containing at least one selected from a water-absorbing amino acid or a salt thereof, and yeast extracts. Granules can be produced easily and efficiently in a short time.
According to the method for producing a tablet of the present invention, it is possible to suppress blocking in the granulation step despite containing at least one selected from a water-absorbing amino acid or a salt thereof and yeast extract, Since sticking in the tableting process can also be suppressed, tablets can be produced easily and efficiently in a short time.
The granules and tablets of the present invention can be suitably used for dietary supplements and supplements used for supplementing water-absorbing amino acids and the like.

Claims (10)

Mixing at least one selected from water-absorbing amino acids or salts thereof and yeast extracts, and a water absorption inhibitor;
And granulating the mixture obtained in the mixing step,
The method for producing granules, wherein the water absorption inhibitor is silicate.   The amount of the silicate with respect to at least one selected from a water-absorbing amino acid or a salt thereof, and a yeast extract is a mass ratio (at least selected from a silicate / water-absorbing amino acid or a salt thereof, and a yeast extract). The method for producing granules according to claim 1, which is 0.01 to 10.0.   The method for producing granules according to any one of claims 1 to 2, wherein at least one selected from water-absorbing amino acids or salts thereof and yeast extracts contains at least one of arginine-glutamate and glutamic acid.   A granule produced by the production method according to claim 1. A water-absorbing amino acid or a salt thereof, and at least one selected from yeast extracts, and a water absorption inhibitor,
The water absorption inhibitor is a silicate;
The amount of the silicate with respect to at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). Granules characterized by being 0.01 to 10.0 at least one). Mixing at least one selected from water-absorbing amino acids or salts thereof and yeast extracts, and a water absorption inhibitor;
Granulating the mixture obtained in the mixing step;
Tableting the granules obtained in the granulation step,
The tablet production method, wherein the water absorption inhibitor is a silicate.   The amount of silicate with respect to at least one selected from water-absorbing amino acids or salts thereof and yeast extracts is a mass ratio (silicate / water-absorbing amino acids or salts thereof and at least one selected from yeast extracts). The method for producing a tablet according to claim 6, wherein the seed is 0.01 to 10.0.   The method for producing a tablet according to any one of claims 6 to 7, wherein at least one selected from water-absorbing amino acids or salts thereof and yeast extracts contains at least one of arginine-glutamate and glutamic acid.   A tablet produced by the production method according to claim 6. A water-absorbing amino acid or a salt thereof, and at least one selected from yeast extracts, and a water absorption inhibitor,
The water absorption inhibitor is a silicate;
The amount of the silicate with respect to at least one selected from the water-absorbing amino acids or salts thereof and yeast extracts is selected from a mass ratio (silicate / water-absorbing amino acids or salts thereof and yeast extracts). A tablet characterized in that it is 0.01 to 10.0.