Method for producing granules and granules

Abstract

To provide a method for producing a granule in which functional material is retained and that is excellent in fluidity.SOLUTION: A method for producing granule comprises:a step of obtaining a mixed suspension that contains at least one selected from a group consisting of crystalline sugar and crystalline sugar alcohol and a functional material and in which a part of the sugar and / or sugar alcohol is contained in a crystalline state, and a step of spraying-drying the mixed suspension under a low temperature condition.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing granules and the granules.

Background Art

[0002] Enzymes, yeasts, flavors, etc. are low-stability functional materials that are easily affected by environmental changes such as heat and acids. When using such components in food and pharmaceutical applications, it is important to maintain stability assuming environmental changes such as temperature and humidity. For example, Patent Document 1 describes a method for obtaining a dry-stabilized composition of a bioactive material by mixing a bioactive material such as a protein or an enzyme with other components in an aqueous solvent to form a viscous slurry, instantaneously freezing this slurry in liquid nitrogen, and further drying this under vacuum.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] The composition in the dry state as described in Patent Document 1 may be used in a powdery or granular form. When using a powdery material in food and pharmaceuticals, excellent fluidity is required from the viewpoints of preventing lumping and preventing clogging in the line.

[0005] One aspect of the present invention aims to provide a method for producing granules having excellent fluidity in which a functional material is retained.

Means for Solving the Problems

[0006] The inventors of the present invention have discovered that by using a suspension of sugars in which some crystalline sugars and / or sugar alcohols exist in a crystalline state, and spray-drying it together with a functional material under low-temperature conditions, granules containing the functional material exhibit excellent fluidity, thereby completing the present invention.

[0007] In one aspect, the present invention provides a method for producing granules comprising the steps of: obtaining a mixed suspension containing at least one selected from the group consisting of crystalline sugars and crystalline sugar alcohols, and a functional material, wherein a portion of the sugar and / or sugar alcohol is contained in a crystalline state; and spray-drying the mixed suspension under low-temperature conditions. Preferably, the spray-drying is carried out under conditions where the inlet air temperature is 0 to 60°C.

[0008] Another aspect of the present invention provides granules containing at least one selected from the group consisting of crystalline sugars and crystalline sugar alcohols, and a functional material, wherein the sugar and / or sugar alcohol are partially in a crystalline state and partially in an amorphous state.

[0009] In the granules, preferably, amorphous sugars and / or sugar alcohols and functional materials are held in the gaps formed between crystalline sugars and / or sugar alcohols.

[0010] In the above-described granules or method for producing the same, the sugars and sugar alcohols are preferably monosaccharides, disaccharides, trisaccharides, and their sugar alcohols. The average particle size of the crystalline sugars and / or sugar alcohols may be 1 to 80 μm. The functional material may be an enzyme, a microorganism, or a fragrance. [Effects of the Invention]

[0011] According to one aspect of the present invention, it is possible to provide a method for producing granules with excellent fluidity in which functional materials are retained. [Brief explanation of the drawing]

[0012] [Figure 1] These are the results of observing sugar suspension A and sugar suspension B using a digital microscope. [Figure 2]These are the results of scanning electron microscopy (SEM) observations of the granular particles relating to Examples 1 to 3. [Figure 3] This is the result of observing sugar suspension D using a digital microscope. [Figure 4] This shows the results of observation using a scanning electron microscope (SEM) of the granular particles according to Example 4. [Figure 5] These are the results of scanning electron microscopy (SEM) observations of granular particles relating to Example 5 and Comparative Examples 1-2. [Figure 6] These are the results of scanning electron microscopy (SEM) observations of the granular particles in Example 6 and Comparative Example 3. [Figure 7] This shows the results of observation using a scanning electron microscope (SEM) of the granular particles according to Example 7. [Figure 8] This shows the results of observation using a scanning electron microscope (SEM) of the granular particles according to Example 8. [Figure 9] This shows the results of observation using a scanning electron microscope (SEM) of the granular particles according to Example 9. [Modes for carrying out the invention]

[0013] Embodiments of the present invention will be described in detail below. However, the present invention is not limited to the following embodiments.

[0014] <Method for producing granules> One embodiment of the present invention is a method for producing granules, comprising the steps of: obtaining a mixed suspension containing at least one selected from the group consisting of crystalline sugars and crystalline sugar alcohols, and a functional material, wherein a portion of the sugar and / or sugar alcohol is contained in a crystalline state (mixing step); and spray-drying the mixed suspension under low temperature conditions (spray-drying step).

[0015] First, the mixing process will be described. In the mixing process, in one embodiment, it includes a step of crystallizing a solution containing at least one selected from the group consisting of crystalline sugar and crystalline sugar alcohol (crystallization step), and a step of adding a functional material (addition step).

[0016] In the crystallization step, first, a solution (sugar solution) containing crystalline sugar and / or crystalline sugar alcohol is prepared. The solution may contain at least one selected from the group consisting of crystalline sugar and crystalline sugar alcohol and a solvent. The solvent is, for example, an organic solvent such as ethanol, methanol, acetone, isopropanol, or water.

[0017] From the perspective of enhancing the operability in the mixing process, the crystalline sugar and crystalline sugar alcohol are preferably monosaccharides, disaccharides, trisaccharides, and their sugar alcohols.

[0018] Examples of monosaccharides include glucose, galactose, mannose, fructose, allose, alulose, etc. Examples of disaccharides include isomaltulose, sucrose, lactulose, lactose, maltose, trehalose, cellobiose, etc. Examples of trisaccharides include nigero triose, maltotriose, raffinose, etc. Note that isomaltulose is a disaccharide trademarked by Mitsui Sugar Co., Ltd. as "palatinose".

[0019] Examples of sugar alcohols include sorbitol, erythritol, xylitol, maltitol, lactitol, mannitol, α - glucopyranosyl - 1,1 - mannitol, α - glucopyranosyl - 1,6 - sorbitol, etc.

[0020] The above - mentioned crystalline sugar and sugar alcohol may be used alone or in combination of two or more.

[0021] The content of sugars and / or sugar alcohols in the sugar solution is not particularly limited as long as it is at a concentration at which crystals are formed in the crystallization step described later. From the viewpoint of efficiently crystallizing in the crystallization step, the content of crystalline sugars and / or sugar alcohols in the sugar solution is preferably 40% by mass or more, more preferably 45% by mass or more, and even more preferably 50% by mass or more, based on the total amount of the sugar solution. From the viewpoint of maintaining good operability in the mixing step and the spray drying step, the content of crystalline sugars and / or sugar alcohols is preferably 90% by mass or less, more preferably 80% by mass or less, and even more preferably 70% by mass or less, based on the total amount of the sugar solution. The content of sugars and / or sugar alcohols may be at a concentration above the saturation solubility. That is, the sugar solution may be a supersaturated solution.

[0022] The Brix value (Bx) of the sugar solution is preferably 50 or higher, more preferably 55 or higher, and even more preferably 65 or higher, from the viewpoint of efficient crystallization in the crystallization process, and preferably 85 or lower, more preferably 80 or lower, and even more preferably 75 or lower, from the viewpoint of maintaining good operability in the mixing and spray drying processes. In this specification, the Brix value (Bx) refers to the ref-Brix value calculated from the refractive index of the sugar solution, and can be measured by a Brix meter (for example, a digital refractometer (RX-5000), manufactured by Atago Co., Ltd.).

[0023] When preparing a sugar solution, the solvent may be heated before adding and dissolving the crystalline sugar and / or sugar alcohol. In this case, the temperature of the solvent is not particularly limited, but for example, it is 70°C or higher. The temperature of the solvent may also be 100°C or lower.

[0024] The sugar solution may contain components other than crystalline sugars and / or sugar alcohols. For example, the sugar solution may contain amorphous sugars and amorphous sugar alcohols. Preferably, the sugar solution contains only crystalline sugars and / or sugar alcohols.

[0025] In the crystallization process, for example, a portion of the crystalline sugar and / or sugar alcohol may be crystallized by cooling the sugar solution (cooling crystallization method), or by reaction crystallization. This makes it possible to obtain a suspension (sugar suspension) containing crystalline sugar and / or sugar alcohol and amorphous sugar and / or sugar alcohol. In the present invention, "crystalline sugar and / or sugar alcohol" means solid sugar and / or sugar alcohol in which the constituent atoms consist of regularly repeating structures in three dimensions, and "amorphous sugar and / or sugar alcohol" means solid or liquid sugar and / or sugar alcohol that does not have such regularly repeating structures.

[0026] When crystallization is performed by the cooling crystallization method, the temperature of the sugar solution due to cooling (cooling temperature) may be set according to the type of crystalline sugar and / or sugar alcohol, for example, 60°C or lower, 50°C or lower, or 45°C or lower. The cooling temperature may also be 5°C or higher, 10°C or higher, 15°C or higher, or 20°C or higher.

[0027] In the crystallization process, means may be used to control crystal growth in order to adjust the average particle size of the crystals. This means may be carried out by a so-called build-up method, for example, by crystallizing while performing ultrasonic irradiation. That is, the crystallization process may further include a step of performing ultrasonic irradiation (ultrasonic irradiation step). Ultrasonic irradiation can be performed, for example, in the crystallization operation by cooling the sugar solution described above, on the sugar suspension obtained using an ultrasonic irradiation device (for example, ULTRA SONIC HOMOGENIZER UH-500 manufactured by SMT Corporation). The ultrasonic irradiation conditions (frequency of ultrasonic irradiation, temperature of the sugar suspension, ultrasonic irradiation time) may be adjusted as appropriate according to the average particle size of the target crystals. When the ultrasonic irradiation step is performed, the liquid after ultrasonic irradiation can be used as the sugar suspension.

[0028] The crystallization rate in the crystallization process is preferably 10% by mass or more, more preferably 20% by mass or more, and even more preferably 30% by mass or more, from the viewpoint of easily obtaining granules with excellent fluidity. The crystallization rate is preferably 80% by mass or less, more preferably 60% by mass or less, and even more preferably 40% by mass or less, from the viewpoint of maintaining good operability in the spray drying process. The crystallization rate in this specification is calculated by placing 1 g of the sugar suspension in a 1.5 ml Eppendorf tube, centrifuging it at 16,000 rpm for 1 minute using a centrifuge (for example, an M150IV manufactured by Sakuma Seisakusho Co., Ltd.), discarding the supernatant, and dividing the remaining amount of crystals by the mass of the sugar suspension.

[0029] The crystallization rate can be adjusted by physically or chemically adding or removing crystals, such as by filter filtration, centrifugation, gravity sedimentation, dissolution by adding water / heating, or adjusting the consumption of crystalline components due to chemical reactions. Alternatively, it can be adjusted by operations that increase the amount of crystals, such as crystallization operations (cooling crystallization, evaporation crystallization, non-solvent crystallization, reaction crystallization, salting-out), or by adding and mixing crystalline components.

[0030] The sugar suspension only needs to contain crystal nuclei, and the size of the crystal nuclei is not particularly limited as long as they are large enough to exist stably in the sugar suspension. For example, the size of the crystal nuclei may be larger than the critical crystal nucleus.

[0031] The average particle size of the crystalline sugar and / or sugar alcohol obtained by the crystallization process is preferably 1 μm or more, more preferably 5 μm or more, even more preferably 10 μm or more, and particularly preferably 20 μm or more, from the viewpoint of maintaining the fluidity of the granules, and preferably 80 μm or less, more preferably 70 μm or less, and even more preferably 60 μm or less, from the viewpoint of preventing the collapse of the granules. In other words, the average particle size of the crystalline sugar and sugar alcohol may be 1 to 80 μm, or 5 to 80 μm. The average particle size of the crystals can be adjusted by adding or removing solvent or solute, changing the solvent temperature, dissolution time, stirring time, crushing with a stirrer or pulverizer, fractionation by filtration, crystallization by hydrolysis of sugar, etc.

[0032] In this specification, the average particle size can be measured using a digital microscope. For measurement, for example, the SKM-S31B-PC manufactured by Saito Optical Co., Ltd. can be used. Using a digital microscope, the major axes of 10 or more crystalline sugars and / or sugar alcohols constituting any 10 or more granules or crystallized grains are measured, and the average value of the measured major axes is calculated and referred to as the "average particle size."

[0033] The crystallization process may further include a step of shearing the crystallized crystals (shearing step) in order to adjust the average particle size of the crystals. The shearing step may be carried out by a so-called breakdown method, in which the average particle size is adjusted by physically impacting the crystals contained in the sugar solution to crush them. In this case, the shearing step can be carried out, for example, after the crystallization by cooling the sugar solution as described above, using a high-pressure homogenizer (for example, HV-0A1-1.5S manufactured by Izumi Food Machinery Co., Ltd.) on the resulting sugar suspension. The shearing conditions (temperature of the sugar suspension, load pressure of the homogenizer, and homogenization conditions) may be adjusted as appropriate according to the average particle size of the crystals. When a shearing step is performed, the liquid after shearing can be used as the sugar suspension.

[0034] In the addition step, in one embodiment, a functional material is added to the sugar suspension. By stirring and mixing the sugar suspension and the functional material, a mixed suspension containing crystalline sugar and / or sugar alcohol, amorphous sugar and / or sugar alcohol, and the functional material can be obtained.

[0035] Functional materials are any material or component that exhibits some function in a composition (e.g., food, pharmaceuticals, etc.) obtained by combining them with other materials. Functional materials may be materials that are affected by the surrounding environment, such as moisture, heat, light, acid, oxygen, molecular motion, ultraviolet light, electrical interactions, and physical stimuli, and may also be materials that lose their function when heated. More specifically, functional materials include amino acids, peptides (including hormones), proteins (including enzymes and antibodies), fatty acids, vitamins, minerals, microorganisms (e.g., bacteria such as lactic acid bacteria, butyric acid bacteria, natto bacteria, bifidobacteria and actinomycetes, molds and yeasts), hormones other than peptides, fragrances, phages, antibiotics other than peptides, etc.

[0036] The amount of functional material added may be 0.01 parts by mass or more, 0.05 parts by mass or more, or 0.1 parts by mass or more, and may be 5 parts by mass or less, 3 parts by mass or less, or 1 part by mass or less, per 100 parts by mass of the sugar suspension described above. The amount of functional material added can be appropriately adjusted depending on the type of functional material.

[0037] In other embodiments, the mixing step described above may be a step in which a mixed suspension is obtained by first preparing a solution containing crystalline sugars and / or sugar alcohols and a functional material, and then carrying out the crystallization step described above. Alternatively, in other embodiments, the mixing step may be a step in which a mixed suspension is prepared containing crystalline sugars and / or sugar alcohols, amorphous sugars and / or sugar alcohols and a functional material.

[0038] Next, the spray drying process will be explained. The spray drying process is a process in which the mixed suspension described above is spray-dried under low temperature conditions.

[0039] In one embodiment, spray drying can be performed using a spray dryer. For example, the OC-16 manufactured by Okawara Chemical Machinery Co., Ltd. can be used as a spray dryer.

[0040] Low-temperature conditions refer to conditions lower than those used in conventional spray drying (e.g., above 60°C), specifically below 60°C. Low-temperature conditions may also be temperature conditions that do not cause loss of the functional material's properties. When spray drying is performed using a sugar solution as the spray liquid, it is necessary to spray dry at high temperatures as in conventional methods to obtain granules. However, in this embodiment, a portion of the sugar solution is crystallized, and a mixed suspension to which the functional material is added is used as the spray liquid. Therefore, suitable granules can be obtained even when spray drying is performed at lower temperatures than conventional methods. For example, if the functional material is an enzyme, enzyme deactivation due to spray drying at high temperatures is suppressed. Also, if the functional material is a fragrance, the volatilization of the fragrance due to spray drying at high temperatures is suppressed. Low-temperature spray drying means that the inlet air temperature (inlet temperature) of the spray dryer is at the temperature conditions described above.

[0041] In one embodiment, the inlet air temperature in the spray drying process is preferably 60°C or lower, 55°C or lower, 50°C or lower, 40°C or lower, 35°C or lower, 30°C or lower, 25°C or lower, 20°C or lower, or 15°C or lower. The inlet air temperature may also be, for example, 0°C or higher, 5°C or higher, or 10°C or higher. That is, the inlet air temperature in the spray drying process may be 0 to 60°C or 0 to 50°C.

[0042] The outlet air temperature (exhaust air temperature) in a spray dryer may be, for example, 50°C or lower, 40°C or lower, 35°C or lower, 30°C or lower, 25°C or lower, 20°C or lower, or 15°C or lower, and may be 0°C or higher, 5°C or higher, or 10°C or higher.

[0043] The liquid temperature of the mixed suspension in the spray drying process may be, for example, 60°C or lower, 50°C or lower, or 45°C or lower, and may be 10°C or higher, 15°C or higher, or 20°C or higher.

[0044] In spray drying, other conditions such as the supply rate of the mixed suspension, ambient temperature, and ambient humidity may be adjusted as appropriate.

[0045] For example, the atomizer rotation speed in spray drying may be 3000 rpm or more, 5000 rpm or more, or 10000 rpm or more, and may be 25000 rpm or less, 20000 rpm or less, or 18000 rpm or less.

[0046] The spray drying process may include a further post-drying step, for example, to adjust the moisture content of the granules. The post-drying step may involve, for example, blowing air onto the granules adhering to the walls of the spray dryer for a predetermined time to further volatilize the moisture from the granules. Alternatively, the granules obtained by spray drying may be stored in a desiccator containing silica gel for a predetermined time.

[0047] <Granules> One embodiment of the present invention contains at least one selected from the group consisting of crystalline sugars and crystalline sugar alcohols, and a functional material, wherein the crystalline sugar and / or sugar alcohol are granules, with a portion being in a crystalline state and the other portion in an amorphous state. The detailed embodiments of the crystalline sugar, crystalline sugar alcohol, and functional material are the same as those described above and are therefore omitted from the description. In this invention, "granules" are aggregates of particles, and the particles constituting the granules (granular particles) contain at least one selected from the group consisting of crystalline sugars and sugar alcohols, and a functional material.

[0048] In one embodiment, the granules consist of granular particles in which a portion of the crystalline sugar and / or sugar alcohol is in a crystalline state, and these crystalline sugars and / or sugar alcohols are aggregated together. In this case, it is preferable that the other portion (other part) of the crystalline sugar and / or sugar alcohol is in an amorphous state and is held in the gaps formed between the aggregated crystalline sugars and / or sugar alcohols. It is also preferable that the functional material is held in the gaps formed between the crystalline sugars and / or sugar alcohols.

[0049] The aggregation of crystalline sugars and / or sugar alcohols can be confirmed by morphological observation of the appearance of granular particles or the fracture surface of granular particles using a scanning electron microscope (SEM) or digital microscope. Furthermore, the retention of amorphous sugars and / or sugar alcohols, as well as functional materials, in the above-mentioned gaps can be confirmed by the following method. (1) Morphological observation of granules during heating is performed using a differential scanning calorimeter (DSC, for example, a RealView DSC (TA7000) manufactured by Hitachi High-Tech Science Corporation). This allows visual confirmation that amorphous sugars and sugar alcohols undergo a glass transition upon heating. (2) Visualize the difference in polarization between the crystalline and amorphous states using a polarizing microscope (for example, a polarizing microscope (MT9200L) manufactured by Meiji Techno Co., Ltd.).

[0050] The number of crystalline sugars and / or sugar alcohols contained in the granular particles (number of crystals) is, for example, 10 or more, but may be 50 or more, or 100 or more. The number of crystals may be 1000 or less. The number of crystals can be measured visually by observation with a scanning electron microscope.

[0051] The median diameter of the granular particles is preferably 30 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more, from the viewpoint of maintaining the fluidity of the granules, and preferably 500 μm or less, more preferably 400 μm or less, and even more preferably 200 μm or less, from the viewpoint of preventing the collapse of the granules. The median diameter of the granular particles can be measured using a laser diffraction particle size distribution analyzer (for example, a SALD-2000J manufactured by Shimadzu Corporation).

[0052] The granular particles may be approximately spherical in shape from the viewpoint of superior fluidity. The granular particles may also have irregularities on their surface from the viewpoint of superior fluidity.

[0053] The granules according to this embodiment can be obtained, for example, by the manufacturing method described above.

[0054] The granules according to the above embodiment exhibit excellent fluidity. As a result, these granules are highly maneuverable. The reason for this is not entirely clear, but the inventors believe that one contributing factor is that the granule particles of this embodiment contain crystalline sugars and / or sugar alcohols, which creates irregularities on the surface of the granule particles, reducing the contact surface between the granule particles. It is also thought that crystalline sugars and / or sugar alcohols are more stable and have lower hygroscopicity and tackiness than amorphous sugars and / or sugar alcohols, thus suppressing adhesion between granule particles. Furthermore, since the granules of this embodiment are obtained by spray drying under low-temperature conditions, the sugars and / or sugar alcohols are more easily maintained in a crystalline state, resulting in granules with excellent fluidity even after spray drying.

[0055] Furthermore, because the granules according to the above embodiment contain crystalline sugars and / or sugar alcohols, the granule particles are less susceptible to deterioration or damage due to physical or mechanical stimuli, and they also exhibit excellent particle structure stability and storage properties.

[0056] Furthermore, the granules according to the above embodiment have interstitial spaces. That is, interstitial spaces are formed within the particles that make up the granules. Because these interstitial spaces allow the solvent to easily penetrate into the interior of the granules, the granules of the present invention also exhibit excellent immediate solubility and immediate disintegration properties.

[0057] Furthermore, since these granules are obtained by spray drying under low-temperature conditions, the functionality of the included functional materials is less likely to be lost due to heat. In other words, the functionality of the functional materials is well retained even after the drying process. Normally, when obtaining granules by spray drying, it is difficult to obtain suitable granules unless spray drying is performed under higher temperature conditions. However, in this embodiment, since a mixed suspension containing crystalline sugars and / or sugar alcohols is used as the spray solution for spray drying, suitable granules can be easily obtained even under low-temperature conditions.

[0058] Furthermore, the granule manufacturing method according to the above embodiment eliminates the need for the step of drying by vacuum freezing or the step of heating the mixed suspension before spray drying, making it possible to manufacture granules containing functional materials in a simpler manner than conventional methods.

[0059] The granules according to the above embodiment can be used, for example, as a material to be added to food, food additives, pharmaceuticals, cosmetics, quasi-drugs, or other pharmaceuticals, animal feed, fertilizers, fragrances, antibiotics, soil conditioners, etc. [Examples]

[0060] The present invention will be described more specifically below with reference to examples. However, the present invention is not limited to the following examples.

[0061] <Example 1> Isomaltulose enzyme reaction solution (manufactured by Mitsui Sugar Co., Ltd.) was added to water and dissolved while being heated to 80°C in a water bath to obtain 5 kg of isomaltulose solution (sugar solution) with a total volume of 65% by mass. This 5 kg of isomaltulose solution was placed in a metal container and rapidly cooled to 30°C. Then, it was treated with a high-pressure homogenizer (manufactured by Izumi Food Machinery Co., Ltd., "HV-0A1-1.5S") at a pressure of 20 MPa and 60 Hz for 2 hours. The treated solution (also called sugar suspension A) was observed with a digital microscope (manufactured by Saito Optical Co., Ltd., "SKM-S31B-PC", magnification: 500x) and it was found that isomaltulose crystals with a particle size of 20 to 80 μm were contained in sugar suspension A. The results of the digital microscope observation of sugar suspension A are shown in Figure 1(a). The crystallization rate of sugar suspension A was 40%.

[0062] A mixed suspension (also called mixed suspension A) was obtained by adding alcohol dehydrogenase (ADH) (manufactured by Oriental Yeast Co., Ltd., "Yeast-derived Alcohol Dehydrogenase", yeast-derived, molecular weight: 141-151 kDa) and bovine serum albumin (BSA) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., "Bovine Serum Albumin") to sugar suspension A in an amount equal to 0.1% by mass on a solid content basis. At this time, the mass ratio of ADH to BSA was set to ADH:BSA = 1:2.

[0063] <Example 2> Isomaltulose (manufactured by Mitsui Sugar Co., Ltd.) was added to water and dissolved while being heated to 80°C in a water bath to obtain 5 kg of isomaltulose solution (sugar solution) with a concentration of 57.5% by mass based on the total volume of the solution. This 5 kg of isomaltulose solution was placed in a metal container and rapidly cooled until the sugar solution reached 30°C. While maintaining a temperature of 35°C or lower, it was processed using a high-pressure homogenizer under the same conditions as in Example 1. When the processed solution (also called sugar suspension B) was observed with a digital microscope (magnification: 500x), isomaltulose crystals of 20-80 μm were found to be contained in sugar suspension B. The results of the digital microscope observation of sugar suspension B are shown in Figure 1(b). The crystallization rate of sugar suspension B was 40%.

[0064] To sugar suspension B, trehalose (Hayashibara Co., Ltd., "Crystalline Trehalose") was added in an amount equal to 5% by mass based on the total amount of solids and trehalose in sugar suspension B, and dissolved. Furthermore, ADH and BSA were added in the same amounts as in Example 1 to obtain a mixed suspension (also called mixed suspension B).

[0065] <Example 3> A mixed suspension (also called mixed suspension C) was obtained in the same manner as in Example 2, except that the amount of trehalose added was changed to an amount equal to 10% by mass.

[0066] [Spray drying] Mixed suspensions A, B, and C were spray-dried using a spray dryer (Okawara Chemical Machinery Co., Ltd., "OC-16") under the conditions shown in Table 1. After 60 minutes of spraying, granules adhering to one half of the spray dryer's canister wall were collected. Subsequently, for mixed suspensions B and C, air was blown for a further 30-40 minutes, and granules adhering to the other half of the spray dryer's canister wall were collected. Hereinafter, granules collected immediately after 60 minutes of spraying will be referred to as "primary dried granules," and granules collected after air blowing will be referred to as "secondary dried granules."

[0067] [Table 1]

[0068] [External observation] The primary dried granules prepared from each mixed suspension were observed using a scanning electron microscope (SEM). The observation results are shown in Figure 2. Figure 2(a) shows the primary dried granules obtained from mixed suspension A, Figure 2(b) shows the primary dried granules obtained from mixed suspension B, and Figure 2(c) shows the primary dried granules obtained from mixed suspension C (magnification: 250x). As shown in each image, it can be seen that the obtained granules are formed by the aggregation of crystalline sugar (isomaltulose). Furthermore, observation of the appearance and cross-section of the granule particles revealed that amorphous solid phases (clumps) of amorphous sugar and functional materials were observed in the gaps formed between the crystalline sugars.

[0069] [Moisture content of granules] The amount of free water contained in each granule was measured using a near-infrared moisture meter (NIR moisture meter KJT-230, manufactured by Kett Scientific Research Institute Co., Ltd.). Furthermore, the total water content of each granule was measured using the following method. Approximately 5g of granules was weighed using an electronic balance (METTLER TOLEDO, "ME204"), and distilled water was added until the total weight reached approximately 25g, at which point the weight was measured. After the granules were completely dissolved, the total solid content in the granule solution was calculated from the refractive index measured using a Refbrics meter (ATAGO Corporation, "RX-5000α"). The difference in weight between the initially measured granule weight and the total solid content of the granule solution was calculated as the total water content of the granules. The results are shown in Table 2.

[0070] [Table 2]

[0071] [Assessment of liquidity] The fluidity of the primary dried granules for each example was evaluated by visual inspection and manual check. The evaluation criteria were as follows. As a result, the fluidity evaluation was "○" for all granules in Examples 1 to 3. ○: Smooth and silky △: It's smooth but hardens when pressed. ×: Sticky or lumpy

[0072] Furthermore, for the primary dried granules in each example, the "flowability index" and "jet index" proposed by R.L. Carr were calculated (Carr, RL, "Evaluating flow properties of solids." Chem.Eng. (1965) 72 (163-168)). For the primary dried granules of each example, the angle of repose (°) and spatula angle (°) of the granules were determined using a multi-functional powder property measuring instrument (Seishin Corporation, "Multi-Tester MT-02"). For the primary dried granules of Example 3, the compressibility (%) and uniformity (-) were further determined, and indices corresponding to each measured value were obtained based on Carr's theory. By summing the indices of each measured value, the flowability index was obtained, and the flowability was evaluated based on Carr's evaluation criteria described in Table 3. The results are shown in Table 4.

[0073] Furthermore, the disintegration angle (°) and difference angle (°) of the primary dried granules for each example were determined using the above apparatus. For the primary dried granules of Example 3, the degree of dispersion (%) was further determined, and the jet-like fluidity index was obtained by adding the index corresponding to each measured value obtained based on Carr's theory with the index based on the fluidity index. The jet-like fluidity of the primary dried granules of Example 3 was evaluated based on Carr's evaluation criteria described in Table 3. The results are shown in Table 4.

[0074] [Table 3]

[0075] [Table 4]

[0076] [Evaluation of enzyme activity (1)] Before performing spray drying, we confirmed the extent to which ADH in the mixed suspension was deactivated over time. The mixed suspension was sampled and diluted with distilled water to an ADH concentration of 0.25 U / mL. After dilution, the ADH was reacted with a substrate under a 25°C atmosphere, and the absorbance of the resulting solution at 340 nm was measured using a spectrophotometer (Shimadzu Corporation, "UVmini-1240"). The absorbance of the ADH reagent adjusted to 0.25 U / mL was set as 100%, and the ratio of absorbance at each elapsed time was defined as the activity retention rate. Table 5 shows the changes in activity retention rate for each mixed suspension.

[0077] [Table 5]

[0078] Table 5 confirms that the enzyme activity was sufficiently maintained during spray drying of the mixed suspensions prepared by the methods described in Examples 1 to 3.

[0079] [Evaluation of enzyme activity (2)] The granules obtained in Examples 1-3 were used to measure the retention rate of ADH activity using the same method as in [Evaluation of Enzyme Activity (1)]. The results are shown in Table 6.

[0080] [Table 6]

[0081] [Evaluation of enzyme activity (3)] The changes in enzyme activity during low-temperature storage were confirmed for the primary dried granules according to Example 1, and for the primary dried granules and secondary dried granules according to Example 2. Each granule was placed in a resealable aluminum bag (manufactured by Seisan Nipponsha Co., Ltd., Lamizip AL-J) and stored for a predetermined number of days at -20°C and 4°C. The change in the retention rate of activity in each granule during the low-temperature storage period was measured using the same method as described above. The results are shown in Table 7.

[0082] [Table 7]

[0083] <Example 4> Trehalose (Hayashibara Co., Ltd., "Crystalline Trehalose") was added to water and dissolved while being heated to 80°C in a water bath to obtain 5 kg of trehalose solution (sugar solution) with a Brix value (Bx) of 62. This 5 kg of trehalose solution was placed in a metal container and rapidly cooled until the sugar solution reached 30°C. While maintaining a temperature below 30°C, it was treated for 15 minutes at POWER MONITER level 5 using an ultrasonic oscillator (SMT Co., Ltd., "ULTRA SONIC HOMOGENIZER UH-500"). When the treated solution (also called sugar suspension D) was observed with a digital microscope (magnification: 500x), trehalose crystals of 20-80 μm were found to be present in sugar suspension D. The results of the digital microscope observation of sugar suspension D are shown in Figure 3.

[0084] 260 g of sucrose aqueous solution with a Bx of 50 was added to 4 kg of sugar suspension D. Furthermore, ADH and BSA were added in the same amounts as in Example 1 to obtain a mixed suspension (also called mixed suspension D).

[0085] [Spray drying] Mixed suspension D was spray-dried using a spray dryer under the following conditions. After 60 minutes of spraying, granules (primary dried granules) adhering to one half of the spray dryer's canister wall were collected. Then, air was blown for another 30-40 minutes, and granules (secondary dried granules) adhering to the other half of the spray dryer's canister wall were collected. <Spray drying conditions> Ambient temperature: 28.4~28.6℃ Ambient humidity: 33-35% Inlet air temperature: 30.2℃ Outlet air temperature: 26.1~28.6℃ Supply amount: 40~45mL / min Atomizer rotation speed: 15118~17081rpm Airflow: 60Hz Exhaust air volume: 37Hz

[0086] [External observation] The primary dried granules according to Example 4 were observed using a scanning electron microscope (SEM) to examine the appearance of the granule particles (magnification: 1000x). The observation results are shown in Figure 4. As shown in Figure 4, it can be seen that the obtained primary dried granules are formed by the aggregation of crystalline sugar (trehalose). Furthermore, when the appearance and cross-section of the granule particles were observed, amorphous solid phases (clumps) of amorphous sugar and functional materials were observed in the gaps formed between the crystalline sugars.

[0087] [Assessment of liquidity] The fluidity of the primary dried granules in Example 4 was evaluated by visual inspection and manual check based on the evaluation criteria described above. As a result, the fluidity was evaluated as "○".

[0088] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the primary dried granules according to Example 4, which are indicators of fluidity, and the disintegration angle (°) and difference angle (°), which are indicators of jet-like flowability, were determined. As a result, the angle of repose was 32.5°, the spatula angle was 34.1°, the disintegration angle was 20.5°, and the difference angle was 12.0°.

[0089] [Adjustment of water activity] Granules with different water activity were prepared from the granules according to Example 4. Granules (Granule X) were prepared by packaging the secondary dried granules according to Example 4 in aluminum foil, and granules (Granule Y) were prepared by vacuum drying the primary dried granules according to Example 4 at room temperature (24-27°C) for 20 minutes, and then placing them in a desiccator humidified to 20-30% RH with silica gel. The water activity of granules X and Y was measured using a water activity meter (Dew Point water activity Meter AquaLAb Series4TE, METER Corporation). As a result, the water activity (Aw) of granule X before the storage test shown below was 0.7561, and the water activity (Aw) of granule Y was 0.4141.

[0090] Granules X, packaged in aluminum foil, and granules Y, stored in a desiccator, were each divided into two systems: one stored at room temperature (24-27°C) and the other in a refrigerator (4-8°C). In other words, for both granules X and granules Y, a system of storage at room temperature and a system of storage in a refrigerator were established.

[0091] [Evaluation of enzyme activity (4)] The absorbance at 340 nm was measured for granules X and Y after storage at room temperature or under refrigeration, using the same method as described in "Evaluation of Enzyme Activity (2)" above. Meanwhile, mixed suspension D was diluted with distilled water to an ADH concentration of 0.25 U / mL. After dilution, the ADH was reacted with a substrate under an atmosphere of 25°C, and the absorbance at 340 nm of the resulting solution was measured using a spectrophotometer. The absorbance measured from mixed suspension D was set as 100%, and the absorbance measured from each granule was defined as the activity retention rate. The change in activity retention rate with respect to storage time is shown in Table 8.

[0092] [Table 8]

[0093] <Example 5, Comparative Examples 1-2> A sugar solution (trehalose) was added to warm water and dissolved while being heated to 90°C in a water bath to obtain a sugar solution with a Brix value of 62. This 90°C sugar solution was placed in a metal container and rapidly cooled to 30°C to obtain 4 kg of sugar suspension (also called sugar suspension E). Meanwhile, an enzyme solution was prepared containing 0.248 g of lactate dehydrogenase (LDH) (manufactured by Oriental Yeast Co., Ltd.), 0.322 g of BSA, 130 g of phosphate-buffered saline (pH 7.5), and 130 g of trehalose. This enzyme solution was added to sugar suspension E immediately after it reached 30°C to obtain a mixed suspension (also called mixed suspension E). The BSA, phosphate-buffered saline, and trehalose in the enzyme solution were added as general protective components.

[0094] The mixed suspension E was spray-dried using the spray dryer described above. The granules according to Example 5 were obtained by spray-drying under conditions of an inlet air temperature of 30.0°C and an outlet air temperature of 23.5°C. On the other hand, the granules according to Comparative Example 1 were spray-dried under conditions of an inlet air temperature of 100.0°C and an outlet air temperature of 76.7°C, and the granules according to Comparative Example 2 were obtained by spray-drying under conditions of an inlet air temperature of 165.0°C and an outlet air temperature of 121.4°C. The spray-drying conditions other than temperature were standardized to the following conditions in all examples and comparative examples. Airflow rate: 60.0Hz Exhaust air volume: 37.0Hz Static pressure inside the tower: Slightly positive pressure Atomizer rotation speed: 18,000 rpm Equipment shape: Wet type Supply amount: 42~45mL / min Temperature of the mixed suspension: 26.9~28.0℃

[0095] [External observation] The granules of Example 5 and Comparative Examples 1 and 2 were observed using a scanning electron microscope (SEM). The observation results (magnification: 500x, 1000x) are shown in Figure 5. Figure 5(a) shows the granules (granular particles) of Example 5, Figure 5(b) shows the granules of Comparative Example 1, and Figure 5(c) shows the granules of Comparative Example 2. As shown in Figure 5(a), it can be seen that the granules of Example 5 are formed by the aggregation of crystalline sugars.

[0096] [Assessment of liquidity] The fluidity of the granules in Example 5 and Comparative Examples 1 and 2 was evaluated visually and manually based on the evaluation criteria described above. As a result, the fluidity of the granules in Example 5 was evaluated as ○, but the fluidity of the granules in Comparative Examples 1 and 2 were both evaluated as ×.

[0097] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the granules in Example 5 and Comparative Example 2, which serve as indicators of fluidity, were determined. The results are shown in Table 9.

[0098] [Table 9]

[0099] [Evaluation of enzyme activity] The extent to which LDH activity in the granules was retained over time was investigated using the granules from Example 5 and Comparative Example 2. Granules stored at room temperature (25°C) for a predetermined number of days were collected and diluted with distilled water to an LDH concentration of 0.25 U / mL. After dilution, the granules were reacted with an LDH substrate under a 25°C atmosphere, and the absorbance at 340 nm of the resulting solution was measured using a spectrophotometer (Shimadzu Corporation, "UVmini-1240"). The absorbance of the LDH reagent adjusted to 0.25 U / mL was set as 100%, and the ratio of absorbance at each elapsed day was defined as the activity retention rate. The results are shown in Table 10.

[0100] [Table 10]

[0101] <Example 6, Comparative Example 3> A mixed suspension (also called mixed suspension F) was obtained by the same method as in Example 5, except that LDH was replaced with ADH.

[0102] The mixed suspension F was spray-dried using the spray dryer described above. The granules according to Example 6 were obtained by spray-drying under conditions of an inlet air temperature of 30.0°C and an outlet air temperature of 23.5°C. On the other hand, the granules according to Comparative Example 3 were spray-dried under conditions of an inlet air temperature of 100.0°C and an outlet air temperature of 76.7°C. The spray-drying conditions other than temperature were the same as those in Example 5.

[0103] [External observation] The granules from Example 6 and Comparative Example 3 were observed using a scanning electron microscope (SEM). The observation results (magnification: 500x) are shown in Figure 6. Figure 6(a) shows the granules from Example 6, and Figure 6(b) shows the granules from Comparative Example 3. As shown in Figure 6(a), it can be seen that the granules from Example 6 are formed by the aggregation of crystalline sugars.

[0104] [Assessment of liquidity] The fluidity of the granules in Example 6 and Comparative Example 3 was evaluated visually and manually based on the evaluation criteria described above. As a result, the fluidity of the granules in Example 6 was evaluated as ○, but the fluidity of the granules in Comparative Example 3 was evaluated as ×.

[0105] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the granules in Example 6 and Comparative Example 3, which serve as indicators of fluidity, were determined. The results are shown in Table 11.

[0106] [Table 11]

[0107] <Example 7> Lactic acid bacteria Lb.paracasei JCM8130 T The bacteria were purchased from the RIKEN BioResource Research Center and cultured to be used as a starter culture. The starter culture was cultured in 500 mL of MRS liquid medium at 37°C for 48 hours. The absorbance of the obtained culture solution at 660 nm was measured to confirm that the lactic acid bacteria culture solution was in a steady state. The supernatant was removed from the MRS medium after culturing, and the precipitate fraction was obtained as a concentrated pellet of lactic acid bacteria. To the obtained pellet of lactic acid bacteria, 130 g of trehalose, 26.1 g of skim milk, 2.61 g of ascorbic acid, and 130 g of phosphate-buffered saline (pH 7.5) were added as protective agents to prepare the lactic acid bacteria solution. The lactic acid bacteria solution was kept at room temperature at 25°C with stirring until it was mixed with the sugar suspension described later. Meanwhile, 4 kg of sugar suspension E was prepared in the same manner as in Example 5. The lactic acid bacteria solution was added to sugar suspension E at 30°C to obtain a mixed suspension (also called mixed suspension G).

[0108] The mixed suspension G was spray-dried using the spray dryer described above to obtain the granules according to Example 7. At this time, all spray-drying conditions were the same as those in Example 5.

[0109] [External observation] The granules according to Example 7 were observed using a scanning electron microscope (SEM). The observation results (magnification: 1000x) are shown in Figure 7. As shown in Figure 7, it can be seen that the granules according to Example 7 are formed by the aggregation of crystalline sugars.

[0110] [Assessment of liquidity] The fluidity of the granules in Example 7 was evaluated by visual inspection and manual check based on the evaluation criteria described above. As a result, the fluidity was evaluated as "○".

[0111] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the granules in Example 7, which are indicators of fluidity, and the collapse angle (°) and difference angle (°), which are indicators of jet-like flowability, were determined. As a result, the angle of repose was 32°, the spatula angle was 50.8°, the collapse angle was 21°, and the difference angle was 11°.

[0112] [Evaluation of Lactobacillus Survival Rate] The granules from Example 7 were used to investigate how well the lactic acid bacteria in the granules were retained over time. Granules stored for predetermined days at 4°C, 25°C, and 37°C were subjected to five 100-fold serial dilutions using 2.5 mM phosphate-buffered saline (pH 7.5). 1 mL of each dilution was dropped into a sterile petri dish, and then 20 mL of BCP-added Agal medium, kept warm at 50°C, was poured into the petri dish containing the dilution. After incubation in a 37°C incubator for 72 hours, the number of lactic acid bacteria colonies formed in the petri dish was counted. The number of lactic acid bacteria (CFU / g) contained in 1 g of granules was calculated from the dilution ratio. The change in the number of lactic acid bacteria (Log(CFU / g)) over the elapsed days is shown in Table 12.

[0113] [Table 12]

[0114] <Example 8> A gum arabic solution was prepared by completely dissolving 330 g of gum arabic in 500 g of warm water. The gum arabic solution was adjusted to a liquid temperature of 60°C, and 165 g of medium-chain triglyceride oil (MCT, Nisshin MCT Oil, manufactured by Nisshin Oillio Co., Ltd.) was mixed in. The mixture was then emulsified using an ultrasonic oscillator similar to that in Example 4 at POWER MONITER level 5. The emulsification process consisted of three cycles of 30 seconds of operation followed by 30 seconds of rest. This yielded an MCT emulsion. Meanwhile, 4 kg of sugar suspension E was prepared using the same method as in Example 5. The MCT emulsion was added to the sugar suspension E at 30°C to obtain a mixed suspension (also called mixed suspension H).

[0115] The mixed suspension H was spray-dried using the spray dryer described above to obtain the granules according to Example 8. At this time, all spray-drying conditions were the same as those in Example 5.

[0116] [External observation] The granules according to Example 8 were observed using a scanning electron microscope (SEM). The observation results (magnification: 1000x) are shown in Figure 8. As shown in Figure 8, it can be seen that the granules according to Example 8 are formed by the aggregation of crystalline sugars.

[0117] [Assessment of liquidity] The fluidity of the granules in Example 8 was evaluated by visual inspection and manual check based on the evaluation criteria described above. As a result, the fluidity was evaluated as "○".

[0118] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the granules in Example 8, which are indicators of fluidity, and the collapse angle (°) and difference angle (°), which are indicators of jet-like flowability, were determined. As a result, the angle of repose was 38°, the spatula angle was 49.8°, the collapse angle was 34°, and the difference angle was 4°.

[0119] <Example 9> 40 g of fragrance (vanillin) was heated to 95°C in a dry heat sterilizer to melt it, and then rapidly cooled to 30°C. Meanwhile, 4 kg of sugar suspension E was prepared by the same method as in Example 5. 40 g of vanillin melt at 30°C was mixed with sugar suspension E at 30°C to obtain a mixed suspension (also called mixed suspension I) (vanillin concentration in the solid content of mixed suspension I: 1.59% by mass).

[0120] The mixed suspension I was spray-dried using the spray dryer described above to obtain the granules according to Example 9. At this time, all spray-drying conditions were the same as those in Example 5.

[0121] [External observation] The granules according to Example 9 were observed using a scanning electron microscope (SEM). The observation results (magnification: 1000x) are shown in Figure 9. As shown in Figure 9, it can be seen that the granules according to Example 9 are formed by the aggregation of crystalline sugars.

[0122] [Assessment of liquidity] The fluidity of the granules in Example 9 was evaluated by visual inspection and manual check based on the evaluation criteria described above. As a result, the fluidity was evaluated as "○".

[0123] Furthermore, using the same method as described above, the angle of repose (°) and spatula angle (°) of the granules according to Example 9, which are indicators of fluidity, and the collapse angle (°) and difference angle (°), which are indicators of jet-like flowability, were determined. As a result, the angle of repose was 34°, the spatula angle was 44.3°, the collapse angle was 26.5°, and the difference angle was 7.5°.

[0124] [Sensory evaluation] In the granules of Example 9, the vanillin aroma was strongly retained. To evaluate the vanillin concentration in the granules, a sensory evaluation using the three-point discrimination method was performed as described below.

[0125] First, the following solutions were prepared. (1) Blank: 1240 mg of trehalose was completely dissolved in 1 L of warm water. (2) Granule solution: 1260 mg of the granules according to Example 9 was completely dissolved in 1 L of warm water (dilution ratio that results in a vanillin concentration of 0.02% if the aroma recovery rate is 100%). (3) Non-granular solution: 20 mg of vanillin and 1240 mg of trehalose were completely dissolved in 1 L of warm water (dilution ratio resulting in a vanillin concentration of 0.02%).

[0126] 10 mL of each solution from (1) to (3) was diluted in series (maximum dilution 256 times). 10 mL of each series dilution was placed in a new Falcon tube, and the dilution was dropped onto the tip of a strip of cardboard made from filter paper (manufactured by Advantec Co., Ltd.). Two panelists evaluated the aroma and performed discrimination based on the three-point discrimination method. That is, they checked whether they could distinguish between the diluted granular solution and the diluted non-granular solution for two blank points. The results are shown in Table 13. In Table 13, ○ indicates that the two panelists (Panel 1 and Panel 2) were able to distinguish the aroma of the dilution, and × indicates that they were unable to distinguish it. From the results shown in Table 13, it can be said that the vanillin aroma is sufficiently retained in the granules of Example 9 even after spray drying.

[0127] [Table 13]

[0128] <Example 1: Influence of temperature conditions during spray drying> The degree to which temperature conditions in spray drying affect the fluidity of granules was investigated. Sugars (trehalose:sucrose 95:5) were added to warm water and dissolved while being heated to 90°C in a water bath to obtain a sugar solution with a Brix value of 61. This 90°C sugar solution was placed in a metal container and rapidly cooled to 30°C. While maintaining a temperature of around 30°C, a sugar suspension was obtained by processing with an ultrasonic oscillator similar to that in Example 4 at POWER MONITER level 5 for 15 minutes.

[0129] The sugar suspension was spray-dried under the temperature conditions (inlet air temperature, outlet air temperature) shown in Table 14 below to obtain granules. The spray-drying conditions other than temperature were the same as those in Example 5.

[0130] For each granule, the fluidity was evaluated visually and manually based on the evaluation criteria described above. The results are shown in Table 14.

[0131] [Table 14]

[0132] <Example 2: Effect of Concentration in Sugar Suspensions> The degree to which the concentration (Brix value) of a sugar suspension affects the fluidity of granules was investigated. Sugars (trehalose:sucrose 95:5) were added to warm water and dissolved while being heated to 90°C in a water bath to prepare sugar solutions with Brix values ​​of 50.0, 55.0, and 61.0. Each sugar solution was placed in a metal container and rapidly cooled to 30°C to obtain sugar suspensions.

[0133] Each sugar suspension was spray-dried using the spray dryer described above to obtain granules. The spray-drying conditions were the same as those in Example 5.

[0134] For each granule, the fluidity was evaluated visually and manually based on the evaluation criteria described above. As a result, all granules obtained from sugar solutions with Brix values ​​of 50.0, 55.0, and 61.0 received a good fluidity rating.

[0135] <Reference Example 3: Effect of atomizer rotation speed during spray drying> The degree to which atomizer rotation speed affects granule fluidity during spray drying was investigated. Sugars (trehalose:sucrose = 95:5) were added to warm water and dissolved while being heated to 90°C in a water bath to obtain a sugar solution with a Brix value of 61. This 90°C sugar solution was placed in a metal container and rapidly cooled to 30°C to obtain a sugar suspension.

[0136] The sugar suspension was spray-dried under atomizer rotation speeds of 5000 rpm, 10000 rpm, and 18000 rpm, respectively, to obtain granules. The spray-drying conditions other than the atomizer rotation speed were the same as those in Example 5.

[0137] For each granule, the fluidity was evaluated visually and manually based on the evaluation criteria described above. As a result, all granules spray-dried at atomizer rotation speeds of 5000 rpm, 10000 rpm, and 18000 rpm received a good fluidity rating.

Claims

1. A step of obtaining a solution containing at least one selected from the group consisting of crystalline sugars and crystalline sugar alcohols (excluding mannitol and maltitol), A step of crystallizing a portion of the sugar and / or sugar alcohol in the solution to obtain a sugar suspension containing a portion of the sugar and / or sugar alcohol in a crystalline state, A step of adding a functional material to the sugar suspension to obtain a mixed suspension, The process comprises, in this order, spray-drying the mixed suspension under low-temperature conditions, The aforementioned spray drying is performed under conditions where the inlet air temperature is 0 to 60°C. The average particle size of the crystalline sugar and / or sugar alcohol is 1 to 80 μm. A method for producing granules, wherein the crystallization rate of the crystalline sugar and / or sugar alcohol is 10% by mass or more and 80% by mass or less, based on the total amount of the sugar suspension.

2. The manufacturing method according to claim 1, wherein the sugar and the sugar alcohol are monosaccharides, disaccharides, trisaccharides, and sugar alcohols thereof.

3. The manufacturing method according to claim 1 or 2, wherein the functional material is an enzyme or a microorganism.

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