Method for producing granular composition containing glutathione

Abstract

This method is for producing a granular composition containing glutathione, and suppresses deterioration in productivity caused by a significant increase in bonding strength between solid raw materials during granulation.　At least one embodiment of the present invention pertains to a method for producing a granular composition containing glutathione, the method comprising granulating a raw material mixture which contains glutathione and a water-soluble nitrogen-containing fertilizer component having a solubility of 10% or less with respect to water at 20°C, and in which the contained amount, of a mineral carrier, based on a dried product thereof is 1 mass% or less.

Description

Method for producing a granular composition containing glutathione

[0001] The present invention relates to a method for producing a granular composition containing glutathione.

[0002] Glutathione is a peptide composed of three amino acids: L-cysteine, L-glutamic acid, and glycine. It is present not only in the human body but also in many other living organisms, including other animals, plants, and microorganisms. It is an important compound for the body, with functions such as scavenging active oxygen, detoxification, and amino acid metabolism.

[0003] Glutathione exists in the body in one of two forms: reduced glutathione (N-(N-γ-L-glutamyl-L-cysteinyl)glycine, hereinafter sometimes referred to as "GSH"), in which the thiol group of the L-cysteine ​​residue is reduced to form SH, and oxidized glutathione (hereinafter sometimes referred to as "GSSG"), in which the thiol group of the L-cysteine ​​residue of two molecules of GSH is oxidized to form a disulfide bond between the two glutathione molecules. Glutathione is known to be useful in fields such as fertilizers, pharmaceuticals, and cosmetics.

[0004] On the other hand, allantoin (5-ureidohydantoin) is an intermediate product produced in the decomposition process of nucleic acid bases (purine bases). In plants, allantoin is produced from 5-hydroxyisouric acid by allantoin synthase (AS) and is decomposed into allantoic acid by allantoinase (ALN). Non-Patent Document 1 discloses that an aln-1 mutant strain in Arabidopsis thaliana, which has been mutated by disrupting the ALN gene so that allantoin accumulates in the plant body, has higher drought stress tolerance than a wild-type strain.

[0005] Patent Document 1 describes that when a material (solid component) containing glutathione is granulated while adding a liquid binder such as water, the binding strength (stickiness) of the material significantly increases, causing the material to adhere to the device during granulation, and the particle size of the granulated product increases, making it impossible to obtain granulated products of the desired particle size. Patent Document 1 discloses, as a means of solving this problem, a method for producing a granular composition containing glutathione, in which a liquid binder is added to a solid component containing crystalline glutathione and the granulation is carried out.

[0006] Patent Document 2 discloses a fertilizer composition for application to plant leaves, characterized by containing oxidized glutathione and a fertilizer component. Patent Document 2 describes that the fertilizer composition may be a granular water-soluble preparation. Patent Document 2 further describes that the fertilizer component may be a nitrogen-containing fertilizer such as ammonium sulfate, ammonium nitrate, ammonium chloride, urea, or lime nitrogen.

[0007] Patent Document 3 discloses a high temperature stress tolerance improver containing allantoin as an active ingredient for improving high temperature stress tolerance in plants. Patent Document 3 also describes that the high temperature stress tolerance improver can further contain known fertilizer components.

[0008] Patent Document 4 discloses a glutathione-containing granular fertilizer that has enhanced storage stability of glutathione and sufficient strength, the granular fertilizer containing glutathione and / or a salt thereof, a mineral, and starch, the starch content of which is 12 mass% or more of the total amount of the granular fertilizer. Patent Document 4 also describes that the granular fertilizer can further contain elements useful as fertilizers, such as potassium, nitrogen, and phosphorus.

[0009] Patent Document 5 discloses that in a method for cultivating a licorice plant, which includes a step of cultivating the licorice plant in the presence of glutathione or a derivative thereof, glutathione or a derivative thereof in the form of a granule can be used, and that glutathione or a derivative thereof, or a composition containing the same, may be mixed with a conventionally known agent such as a fertilizer or a plant hormone and then applied to the plant.

[0010] JP 2018-168103 A International Publication No. WO2017 / 006869 JP 2017-137281 A International Publication No. WO2018 / 135612 JP 2017-104102 A

[0011] Watanabe, S. etc. al. , Plant Cell Environ. 37:1022-1036 (2014)

[0012] In a method for producing a granular composition by granulating solid raw materials containing glutathione, as described in Patent Document 1, there is a problem that the bonding strength between the solid raw materials increases significantly during granulation, causing the material to adhere to the equipment during granulation and the granulated material to become coarse, resulting in reduced productivity.

[0013] Therefore, this specification discloses a means for solving the problem of coarsening of granulated products in a method for producing a granular composition containing glutathione by granulation.

[0014] The present inventors have discovered that the above-mentioned problems can be solved by granulating a raw material mixture containing glutathione and a water-soluble nitrogen-containing fertilizer component, such as allantoin, whose solubility in water at 20°C is 10% or less, and in which the mineral carrier content is 1% by mass or less on a dry matter basis, in a method for producing a granular composition containing glutathione. Specifically, this specification discloses the following as a means for solving the above-mentioned problems.

[0015] (1) A method for producing a granular composition containing glutathione, comprising granulating a raw material mixture containing glutathione and a water-soluble nitrogen-containing fertilizer component having a solubility in water at 20°C of 10% or less, the ... water-soluble nitrogen-containing fertilizer component having a content of 1% by mass or less on a dry matter basis of a mineral carrier. (2) The method according to (1), wherein the nitrogen-containing fertilizer component is at least one component selected from allantoin, histidine, and isoleucine. (3) The method according to (1), wherein the nitrogen-containing fertilizer component is allantoin. (4) The method according to any one of (1) to (3), wherein the glutathione is oxidized glutathione. (5) The method according to any one of (1) to (4), wherein the raw material mixture contains 40 parts by mass or more of the nitrogen-containing fertilizer component per 100 parts by mass of the glutathione. (6) The method according to any one of (1) to (5), wherein the raw material mixture further contains one or more inorganic salts selected from a nitrogen-containing inorganic salt, a phosphorus-containing inorganic salt, and a potassium-containing inorganic salt, and the raw material mixture contains the glutathione, the nitrogen-containing fertilizer component, and the inorganic salts in a total amount of 70% by mass or more on a dry matter basis. This specification incorporates the disclosure of Japanese Patent Application No. 2022-034075, from which the present application claims priority.

[0016] According to the method for producing a granular composition containing glutathione disclosed in the present specification, it is possible to suppress a decrease in productivity caused by a significant increase in the bonding strength between solid raw materials during granulation.

[0017] <Glutathione> Glutathione may be reduced glutathione (GSH, N-(N-γ-L-glutamyl-L-cysteinyl)glycine), oxidized glutathione (GSSG) formed by two GSH molecules bound via a disulfide bond, or a mixture of GSH and GSSG. The glutathione is preferably GSSG.

[0018] Glutathione (GSSG or GSH) can include various forms of glutathione, such as a free form that is not bound to other substances and is not ionized, a salt, a hydrate, or a mixture of two or more of these.

[0019] When GSSG is used as glutathione, a mixture of GSSG and GSH may be used, but the content of GSSG is preferably relatively higher than the content of GSH. More preferably, the total weight of GSSG (weight converted into free form) relative to the total weight of GSSG and GSH (weight converted into free form) is 70% by mass or more, more preferably 80% by mass or more, more preferably 90% by mass or more, even more preferably 95% by mass or more, even more preferably 98% by mass or more, and most preferably 100% by mass.

[0020] The salt of GSSG is not particularly limited as long as it is one or more salts acceptable as a fertilizer, such as ammonium salt, calcium salt, magnesium salt, sodium salt, and lithium salt, but is preferably one or more salts selected from ammonium salt, calcium salt, and magnesium salt. Examples of GSSG salts include monoammonium salt of GSSG, 0.5 calcium salt or monocalcium salt of GSSG, and 0.5 magnesium salt or monomagnesium salt of GSSG.

[0021] <Water-Soluble Nitrogen-Containing Fertilizer Component> In one or more embodiments of the method of the present invention, a raw material mixture containing glutathione and a water-soluble nitrogen-containing fertilizer component having a solubility in water of 10% or less at 20°C and a mineral carrier content of 1% by mass or less on a dry matter basis is granulated. This suppresses an increase in the bonding strength between the raw materials during granulation, and prevents adhesion of the materials to the granulation equipment and coarsening of the granulated product, compared to when a raw material mixture not containing the nitrogen-containing fertilizer component is used. Conventionally, a technique of incorporating a mineral carrier such as talc into the granulation raw materials has been known to suppress the bonding strength between the raw materials during granulation and prevent coarsening of the granulated product. However, incorporating a large amount of a water-insoluble mineral carrier into a granular composition containing glutathione can potentially limit its use. In one or more embodiments of the method of the present invention, the above-mentioned objective can be achieved by incorporating the nitrogen-containing fertilizer component into a raw material mixture containing glutathione and a mineral carrier content of 1% by mass or less on a dry matter basis.

[0022] The solubility of the nitrogen-containing fertilizer component in water at 20°C is preferably 0.1% or more, more preferably 0.3% or more, and preferably 3% or less, more preferably 1% or less. Another preferred embodiment is that the solubility of the nitrogen-containing fertilizer component in water at 20°C is 5% or less. Here, the solubility (%) is the ratio, expressed as a percentage, of the mass of the nitrogen-containing fertilizer component that can be dissolved in a predetermined amount of water at 20°C to the mass of the predetermined amount of water. Specifically, it can be expressed as the number of grams of the nitrogen-containing fertilizer component that can be dissolved in 100 ml of water at 20°C. For example, the solubility of a component that dissolves 1 g in 100 ml of water at 20°C can be expressed as 1 g / 100 ml = 1%.

[0023] The nitrogen-containing fertilizer component is, for example, at least one component selected from allantoin, histidine, and isoleucine, and is preferably allantoin. Allantoin is also called 5-ureidohydantoin, and its free form has a structure represented by the following formula:

[0024]

[0025] Allantoin has one asymmetric carbon atom (indicated by * in the formula) and exists in the form of (R)-allantoin and (S)-allantoin. The allantoin used in one or more embodiments of the present invention may be (R)-allantoin, (S)-allantoin, or a mixture thereof. Allantoin can be produced synthetically, for example, from glyoxylic acid and urea. Allantoin may also be derived from or obtained from plants or microorganisms.

[0026] Histidine and isoleucine may be in the L-form, the D-form, or a mixture of the L-form and the D-form, with the L-form being preferred. Histidine and isoleucine may be produced, for example, by organic synthesis techniques or biochemical techniques using enzymes or the like.

[0027] Allantoin may include various forms of allantoin, such as a free form that is not bound to other substances and is not ionized, a salt, a hydrate, a mixture of two or more thereof, etc. Similarly, histidine and isoleucine may include various forms of histidine and isoleucine, such as a free form that is not bound to other substances and is not ionized, a salt, a hydrate, a mixture of two or more thereof, etc.

[0028] <Granular Composition> The use of the granular composition containing glutathione produced by the method according to one or more embodiments of the present invention is not particularly limited. For example, the granular composition can be used for application to plants. The granular composition is obtained by granulating a raw material mixture containing glutathione and the nitrogen-containing fertilizer component, and the mineral carrier has a dry matter content of 1% by mass or less.

[0029] The amount of glutathione in the granular composition is not particularly limited and can be adjusted depending on the application of the granular composition, but can be, for example, 1% by mass or more, preferably 3% by mass or more, more preferably 5% by mass or more, and for example, 40% by mass or less, preferably 20% by mass or less, based on the total amount of the granular composition on a dry matter basis. This range is particularly preferred when the granular composition is used to promote plant growth.

[0030] The shape of the granular composition is not particularly limited as long as it is granular, and granules are an example. The granular shape referred to here may be any shape formed by bonding primary particles of the material together through a granulation operation. The size of the granular composition is not limited, and is, for example, a granule with a maximum diameter of 0.20 mm or more and 2.0 mm or less.

[0031] The granular composition preferably contains no more than 1% by mass of a mineral carrier on a dry basis (including the case where no mineral carrier is contained), more preferably no more than 0.5% by mass, even more preferably no more than 0.2% by mass, and particularly preferably no mineral carrier. Examples of mineral carriers include talc, mica, bentonite, montmorillonite, smectite, clay, kaolin, activated clay, zeolite, diatomaceous earth, perlite, ziegelite, sericite, pumice, silica, white carbon, vermiculite, calcium carbonate, etc., and the total content of these is preferably within the above range.

[0032] In one or more embodiments of the method of the present invention, a raw material mixture containing glutathione and the nitrogen-containing fertilizer component is granulated, the raw material mixture having a mineral carrier content of 1% by mass or less on a dry matter basis. The raw material mixture refers to a mixture of solid raw materials excluding a liquid binder, which will be described later.

[0033] In a more preferred embodiment, the raw material mixture contains preferably 40 parts by mass or more, more preferably 50 parts by mass or more, and more preferably 100 parts by mass or more of the nitrogen-containing fertilizer component per 100 parts by mass of the glutathione. In this case, coarsening of the granular composition during granulation is particularly likely to be suppressed.

[0034] In a more preferred embodiment, the raw material mixture contains preferably 2000 parts by mass or less, more preferably 1800 parts by mass or less, more preferably 1600 parts by mass or less, and particularly preferably 1000 parts by mass or less of the nitrogen-containing fertilizer component per 100 parts by mass of the glutathione. In this case, generation of fine powder during granulation of the granular composition is likely to be suppressed.

[0035] The raw material mixture has a mineral carrier content of 1% by mass or less on a dry basis (including the case where the mineral carrier is not included), more preferably 0.5% by mass or less, even more preferably 0.2% by mass or less, and particularly preferably does not contain a mineral carrier. Examples of the mineral carrier are as described above.

[0036] The raw material mixture may contain inorganic salts, binders, etc. in addition to glutathione and the nitrogen-containing fertilizer components.

[0037] As the inorganic salt, inorganic salts containing elements useful as fertilizers, such as potassium, nitrogen, phosphorus, calcium, and magnesium, are preferred, and one or more inorganic salts selected from nitrogen-containing inorganic salts, phosphorus-containing inorganic salts, and potassium-containing inorganic salts are particularly preferred.

[0038] Specific examples of nitrogen-containing inorganic salts include ammonium sulfate and ammonium dihydrogen phosphate. Specific examples of phosphorus-containing inorganic salts include ammonium dihydrogen phosphate. Specific examples of potassium-containing inorganic salts include potassium sulfate.

[0039] In an embodiment in which the raw material mixture contains glutathione, the nitrogen-containing fertilizer component, and one or more inorganic salts selected from a nitrogen-containing inorganic salt, a phosphorus-containing inorganic salt, and a potassium-containing inorganic salt, the raw material mixture contains, on a dry matter basis, preferably 70% by mass or more, more preferably 80% by mass or more, more preferably 90% by mass or more, and even more preferably 95% by mass or more of the glutathione, the nitrogen-containing fertilizer component, and the inorganic salt in total. According to this embodiment, a granular composition having high water solubility and suitable for application to plants can be obtained. In this embodiment, the raw material mixture contains, on a dry matter basis, preferably 100% by mass or less, more preferably 99% by mass or less of the glutathione, the nitrogen-containing fertilizer component, and the inorganic salt in total.

[0040] Examples of binders include carboxymethyl cellulose, methyl cellulose, ethyl cellulose, polyvinylpyrrolidone, pullulan, acrylic acid polymers, polyvinyl alcohol, gelatin, agar, gum arabic, powdered gum arabic, xanthan gum, toran gum, guar gum, gellan gum, locust bean gum, pregelatinized starch, macrogol, starch, soluble starch, dextrin, tragacanth gum, β-glucan, pectin, casein, soy protein, hydroxyethyl cellulose, acetyl cellulose, lignosulfonic acid, carboxymethyl starch, hydroxyethyl starch, polyvinyl methyl ether, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, shellac, rosin, tall oil, ester gum, polyvinyl Examples of the surfactant include acetate, polylactic acid, polyvinyl chloride, polyester, polyurea, polyamide, coumarone resin, biodegradable polymer, paraffin wax, microcrystalline wax, petrolatum, montan wax, carnauba wax, cotton wax, beeswax, wool wax, polymeric nonionic surfactants, polymeric anionic surfactants, polymeric cationic surfactants, polymeric amphoteric surfactants, alginic acid (all of which are polymeric compounds), sodium silicate, glycerin, animal and vegetable oils, fats and oils, liquid paraffin, heavy oil, glucose, sucrose, mannitol, sorbitol, non-polymeric nonionic surfactants, non-polymeric anionic surfactants, non-polymeric cationic surfactants, non-polymeric amphoteric surfactants (all of which are non-polymeric compounds), and salts thereof, and at least one selected from these groups can be used.

[0041] Particularly preferred binders are polymeric binders, and particularly preferred are at least one selected from carboxymethylcellulose and its salts, polyvinyl alcohol, starch, gum arabic, hydroxyethyl cellulose, lignosulfonic acid and its salts, and polyethylene glycol. Examples of carboxymethylcellulose salts include alkali metal salts such as sodium, potassium, and lithium, and alkaline earth metal salts such as magnesium and calcium. Carboxymethylcellulose and its salts are also thought to contribute to improving the storage stability of glutathione in the composition. The use of these binders may enable sustained release of glutathione when the granular composition is applied to plants. When at least one binder selected from carboxymethylcellulose and its salts, polyvinyl alcohol, starch, gum arabic, hydroxyethyl cellulose, lignosulfonic acid and its salts, and polyethylene glycol is used as the binder, the total content of the granular composition and the raw material mixture on a dry matter basis is preferably 0.5 to 5% by mass, more preferably 1 to 3% by mass.

[0042] Another example of a preferred binder is a non-polymeric anionic surfactant, particularly a linear alkylbenzene sulfonic acid or a salt thereof. When a non-polymeric anionic surfactant is used as a binder, the total content of the non-polymeric anionic surfactant relative to the total amount of the granular composition and the raw material mixture on a dry matter basis is preferably 0.3 to 3 mass%, more preferably 0.5 to 2 mass%.

[0043] The raw material mixture may further contain an organic carrier, an excipient, and the like.

[0044] Examples of organic carriers include dried plant materials such as rice husks, sawdust, soybean flour, corn stalks, and plant fibers, as well as organic porous carriers such as pulp flock and activated carbon.

[0045] Examples of excipients include lactose, trehalose, cellulose, and the like.

[0046] <Method for producing granular composition> A method for producing a granular composition containing glutathione according to one or more embodiments of the present invention is characterized by comprising granulating a raw material mixture containing glutathione and the nitrogen-containing fertilizer component, the raw material mixture containing 1% by mass or less of the mineral carrier on a dry matter basis.

[0047] According to the method of this embodiment, the increase in the bonding strength between the raw materials during granulation can be suppressed, and the adhesion of the materials to the equipment during granulation and the coarsening of the granulated material can be suppressed, thereby resulting in high productivity of the granular composition.

[0048] The granulation method is not particularly limited, and granulation methods such as stirring granulation and extrusion granulation can be used.

[0049] The raw material mixture to be subjected to granulation is a powdered solid raw material mixture having an average particle size of preferably 55 to 210 μm, more preferably 60 to 200 μm, and even more preferably 71 to 200 μm. The powdered solid raw material mixture having an average particle size in the above range preferably contains 70% by mass or more, and more preferably 80% by mass or more, of particles having a particle size in the range of 20 to 500 μm.

[0050] It is preferable to carry out a pulverization step, in which the raw material mixture is pulverized to an average particle size within the above range, before granulation. The pulverization step can be carried out using a mixer, a mill, or the like.

[0051] In this specification, the particle size of the raw material mixture refers to the spherical equivalent diameter of the particles of the raw material mixture determined by a light scattering method (calculating the particle size from the scattering state of light when a sample is irradiated with laser light). An example of an apparatus for measuring particle size by the light scattering method is the LA-960 laser diffraction / scattering particle size distribution analyzer manufactured by Horiba, Ltd. The average particle size of the raw material mixture refers to an average value calculated by weighting by volume from the particle size distribution of the raw material mixture determined by the light scattering method.

[0052] The granulation step is preferably a step of stirring the raw material mixture together with a liquid binder. Examples of the liquid binder include liquids such as water and alcohol, as well as blackstrap molasses and pulp waste liquor, which may be used alone or in combination. Alternatively, the liquid binder may be prepared by dissolving the aforementioned binding agent in a liquid such as water or alcohol. Water is particularly preferred as the liquid binder.

[0053] The granulation step can be carried out under suitable conditions so as to obtain a granular composition having a size suitable for the intended use.

[0054] The granulation step preferably further includes a drying step in which the granular composition is dried to remove volatile components derived from the raw material mixture and the liquid binder. If necessary, the granular composition having the desired particle size can be separated and recovered by sieving or the like.

[0055] Experiment 1: Extrusion Granulation A GSSG-containing granular composition was produced by extrusion granulation using a solid raw material mixture containing oxidized glutathione (GSSG) to which an anti-stickiness component had been added. The relationship between the motor load of the granulator during granulation, the proportion of large particles (>1.7 mm) in the granulated product, the proportion of fine particles (<0.25 mm), and the proportion of the anti-stickiness component added was investigated.

[0056] <Raw Materials> The components shown in the table below were used as solid raw materials. Allantoin was used as the stickiness-reducing component. As inorganic salts, a mixture of ammonium sulfate, ammonium dihydrogen phosphate, and potassium sulfate in a mass ratio of 3:4:5 was used. The solubility of allantoin in water at 20°C was 0.5 g / 100 mL (0.5%).

[0057]

[0058] Water was used as the liquid binder.

[0059] <Pulverization> A mixture of solid raw materials prepared according to the formulation shown in Table 1 was pulverized in a pulverizer to an average particle size of approximately 100 μm. Here, the average particle size is a volume-weighted average value calculated from the distribution of equivalent sphere diameters determined by a light scattering method using a laser diffraction / scattering particle size distribution analyzer LA-960 manufactured by Horiba, Ltd.

[0060] <Granulation> 500 g of the pulverized mixture of solid raw materials was weighed, and 50 g of water was added as a liquid binder and kneaded in a mixer. The kneaded mixture was extrusion granulated using an extrusion granulator (MG-55-1 model, manufactured by Dalton) through a screen with a pore size of 0.8 mm. The granules obtained by extrusion granulation were treated for 10 seconds in a sieve (QJ-230T-2 model, manufactured by Dalton) to adjust the particle size, and then dried in a fluidized bed dryer (F-LABO model, manufactured by Nagato Electric Works). The dried product was classified using a vibrating sieve with sieves having 1.7 mm and 0.25 mm openings. The fraction that passed through the 1.7 mm opening sieve but not the 0.25 mm opening sieve was collected as a GSSG-containing granular composition.

[0061] <Results> <Evaluation of Load on Granulator> The motor load on the granulator during extrusion granulation was recorded.

[0062] A motor load of 4.0 amperes or less was evaluated as "good", and a motor load of more than 4.0 amperes was evaluated as "poor".

[0063] The motor load of the granulator when extrusion granulation was performed using solid raw materials of formulations 1 to 6, which had different addition ratios of allantoin, an ingredient used to suppress stickiness, is shown in the table below.

[0064]

[0065] <Evaluation of productivity> The proportion of large particles was determined by calculating the proportion (mass %) of the fraction that could not pass through a sieve with 1.7 mm openings relative to the total amount of the granules after drying. A proportion of large particles of 20 mass % or less was evaluated as "Good", and a proportion of large particles exceeding 20 mass % was evaluated as "Poor".

[0066] The proportion of fine powder was calculated as the proportion (mass %) of the fraction that passed through a sieve with 0.25 mm mesh size relative to the total amount of the dried granules. A fine powder proportion of 20 mass % or less was evaluated as "Good", and a fine powder proportion exceeding 20 mass % was evaluated as "Poor".

[0067] The following table shows the evaluation results of the ratio of large particles and fine powder in extrusion granulation using solid raw materials of formulations 1 to 6, which have different addition ratios of allantoin, an ingredient for suppressing stickiness.

[0068]

[0069] <When allantoin was replaced with serine> Blend 7 was prepared by replacing 20% ​​by mass of allantoin in the solid raw material of Blend 4 with the same amount of serine. Extrusion granulation was carried out in the same manner as above using the solid raw material of Blend 7, and evaluation was carried out. The solubility of serine in water at 20°C was 25 g / 100 mL (25%).

[0070] The evaluation results of the motor load of the granulator and the proportion of large particles and fine powder when the solid raw material of Blend 7 was used for extrusion granulation are shown in the table below.

[0071]

[0072]

[0073] <When allantoin was replaced with L-histidine or L-isoleucine> The allantoin (5, 20, or 80% by mass) in the solid raw material of Blend 2, Blend 4, and Blend 6 was replaced with the same amount of L-histidine to produce Blends 9, 10, and 11, respectively. The solubility of L-histidine in water at 20°C was 4.2 g / 100 mL (4.2%).

[0074] The allantoin (5, 20, or 80% by mass) in the solid raw material of Blend 2, Blend 4, and Blend 6 was replaced with the same amount of L-isoleucine to obtain Blends 12, 13, and 14, respectively. The solubility of L-isoleucine in water at 20°C was 4.0 g / 100 mL (4.0%).

[0075] Formulations 9, 10, 11, 12, 13, and 14 are shown in the table below.

[0076]

[0077] The solid raw materials of Blends 9, 10, 11, 12, 13, and 14 were extrusion granulated in the same manner as above, and evaluation was carried out.

[0078] The evaluation results of the motor load of the granulator and the proportion of large particles and fine powder when extrusion granulation was performed using the solid raw materials of Blends 9, 10, 11, 12, 13, and 14 are shown in the table below.

[0079]

[0080]

[0081] Experiment 2: Stirring granulation A GSSG-containing granular composition was produced by stirring granulation using a solid raw material mixture containing oxidized glutathione (GSSG) to which an anti-stickiness component had been added. After stirring granulation, the relationship between the degree of adhesion of the raw material to the inner wall of the apparatus and the proportion of the anti-stickiness component added was investigated.

[0082] <Raw Materials> The solid raw materials used were the components shown in the table below. Allantoin was used as the stickiness-reducing component. As inorganic salts, a mixture of ammonium sulfate, ammonium dihydrogen phosphate, and potassium sulfate in a mass ratio of 3:4:5 was used.

[0083]

[0084] Water was used as the liquid binder.

[0085] <Pulverization> A mixture of solid raw materials prepared according to the formulation shown in Table 9 was pulverized in a pulverizer to an average particle size of approximately 100 μm. Here, the average particle size is a volume-weighted average value calculated from the distribution of equivalent sphere diameters determined by a light scattering method using a laser diffraction / scattering particle size distribution analyzer LA-960 manufactured by Horiba, Ltd.

[0086] <Granulation> 500 g of the pulverized mixture of solid raw materials was weighed, and 44 g of water was added as a liquid binder in a stirring granulator (SPGJ-2TG model manufactured by Dalton), followed by stirring granulation. The granules obtained by stirring granulation were dried in a fluidized bed dryer (F-LABO model manufactured by Nagato Electric Works, Ltd.).

[0087] <Results> <Evaluation of the load on the granulator> The motor load on the granulator during agitation granulation was recorded.

[0088] A motor load of 3.0 amperes or less was evaluated as "good", and a motor load of more than 3.0 amperes was evaluated as "poor".

[0089] The motor load of the granulator when agitating and granulating the solid raw materials of formulations 1, 8, 2, 4, and 6, which have different addition rates of allantoin, an ingredient used to suppress stickiness, is shown in the table below.

[0090]

[0091] <Evaluation of productivity> After the completion of stirring and granulation, the inside of the apparatus was cleaned with a brush, and then the degree of adhesion of the raw material to the apparatus wall surface close to the stirring blade was visually evaluated. If the adhesion occurred on less than 10% of the circumference of the wall surface, it was evaluated as "Good", if it occurred on 10% to less than 50%, it was evaluated as "Good", and if it occurred on 50% or more, it was evaluated as "Poor".

[0092]

[0093] <When allantoin was replaced with L-histidine or L-isoleucine> The formulation in which allantoin (2% by mass) in the solid raw material of Formula 8 was replaced with the same amount of L-histidine was designated Formula 15. Furthermore, the formulation in which allantoin (2% by mass) in the solid raw material of Formula 8 was replaced with the same amount of L-isoleucine was designated Formula 16.

[0094] The solid raw materials of Blends 10, 13, 15, and 16 were subjected to stirring granulation and evaluation in the same manner as above. Blends 10, 13, 15, and 16 are shown in the table below.

[0095]

[0096] The evaluation results of the motor load of the granulator and the degree of adhesion of the raw materials to the equipment walls when agitating and granulating the solid raw materials of Blends 10, 13, 15, and 16 are shown in the table below.

[0097]

[0098]

[0099] All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety.

[0100] The upper and / or lower limits of the numerical ranges described herein can be arbitrarily combined to define a preferred range. For example, the upper and lower limits of the numerical ranges can be arbitrarily combined to define a preferred range, the upper limits of the numerical ranges can be arbitrarily combined to define a preferred range, and the lower limits of the numerical ranges can be arbitrarily combined to define a preferred range. Furthermore, in this application, numerical ranges expressed using the symbol "to" include the numerical values ​​written before and after the symbol "to" as the upper and lower limits, respectively.

[0101] Throughout this specification, singular terms should be understood to include the plural concept unless otherwise stated. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise stated.

[0102] Although the present embodiment has been described in detail above, the specific configuration is not limited to this embodiment, and even if there are design changes within the scope that do not deviate from the gist of this disclosure, they are included in this disclosure.

Claims

1. A method for producing a granular composition containing glutathione, Granulating a raw material mixture containing glutathione and a water-soluble nitrogen-containing fertilizer component whose solubility in water at 20°C is 10% or less, and whose content on a dry basis of the mineral carrier is 1% by mass or less. A method that includes this.

2. The method according to claim 1, wherein the nitrogen-containing fertilizer component is at least one component selected from allantoin, histidine, and isoleucine.

3. The method according to claim 1, wherein the nitrogen-containing fertilizer component is allantoin.

4. The method according to any one of claims 1 to 3, wherein the glutathione is oxidized glutathione.

5. The method according to any one of claims 1 to 3, wherein the raw material mixture contains 40 parts by mass or more of the nitrogen-containing fertilizer component with respect to 100 parts by mass of the glutathione.

6. The raw material mixture further comprises one or more inorganic salts selected from nitrogen-containing inorganic salts, phosphorus-containing inorganic salts, and potassium-containing inorganic salts. The raw material mixture contains, on a dry basis, glutathione, nitrogen-containing fertilizer components, and inorganic salts in a total amount of 70% by mass or more. The method according to any one of claims 1 to 3.