Method and apparatus for producing solid amino acid mixture

Abstract

To provide a simple and economical granule production process for improving the production efficiency of an amino acid-mixed solid.SOLUTION: A first step of preparing an amino acid mixture solution containing an amino acid, a second step of stirring the amino acid mixture solution to form a thin film and drying and pulverizing the formed thin film to prepare wet granules, and a third step of drying the wet granules to prepare an amino acid mixture solid in a granular formulation, wherein in the second step, the amino acid mixture solution is dried so that a solid concentration in the wet granules is within a range of a granule-forming concentration.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present application relates to a method for producing an amino acid mixed solid and an apparatus for producing an amino acid mixed solid. [Background technology]

[0002] L-amino acids are the basic building blocks of proteins and are used as important raw materials in pharmaceuticals, food additives, animal feed, nutrients, insecticides, fungicides, etc. The target L-amino acids are mainly produced by fermentation using microorganisms or their artificial mutant strains developed by artificial mutation or genetic engineering.

[0003] However, since fermentation produces not only the target L-amino acid but also by-products and waste products, a separation and purification step is necessary after the fermentation process to obtain a specific L-amino acid with high purity. However, since other products contained in the fermented product also contain nutritionally valuable components, there is an increasing demand for products containing the entire fermented product, and there is a particular demand for granular products that are convenient for storage, portability, and intake.

[0004] To granulate a fermented product, the water content in the fermented product is evaporated before the granules are produced, but drying the fermented product requires a large amount of energy. This required energy reduces the efficiency of the granulation process. Furthermore, when granulating a fermented product using a fluidized bed granulator or a mixing granulator according to conventional techniques (such as Patent Document 1), there is a limit to how much the fermented product can be concentrated to increase the solid content, which reduces the efficiency of the process.

[0005] Against this technical background, the inventors have developed a simple and economical granule manufacturing process that improves the production efficiency of amino acid mixed solids by utilizing a thin film drying device in the granulation process, and have completed the present application. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] US Patent Application Publication No. 2015 / 0283527 Summary of the Invention [Problem to be solved by the invention]

[0007] The present application aims to provide a method and apparatus for highly efficiently producing a granular dosage form of an amino acid mixture solid by concentrating the solid concentration in the amino acid mixture solution so that it falls within the range of granule formation concentrations and using the concentrated amino acid mixture solution. [Means for solving the problem]

[0008] These will be described in detail below. Note that each description and embodiment disclosed in this application also applies to other descriptions and embodiments. In other words, all combinations of various elements disclosed in this application are included in this application. Furthermore, this application is not limited to the following specific descriptions.

[0009] FIG. 1 is a flowchart showing a method for producing a solid amino acid mixture according to one embodiment of the present application.

[0010] According to one aspect of the present application, there is provided a method for producing an amino acid mixed solid, comprising a first step S100 of preparing an amino acid mixed solution containing amino acids, a second step S200 of stirring the amino acid mixed solution to form a thin film, and drying and pulverizing the formed thin film to produce wet granules, and a third step S300 of drying the wet granules to produce an amino acid mixed solid in granule dosage form, wherein in the second step S200, the amino acid mixed solution is dried so that the solid concentration in the wet granules is within the range of the granule formation concentration.

[0011] When the above-mentioned method for producing a solid amino acid mixture is used, the amino acid mixture solution can be dried so that the solid concentration falls within the range of the concentration for forming granules, and then produced into a granule dosage form.

[0012] Each step of the method for producing the amino acid mixture solid of the present application will be described below.

[0013] First, a first step S100 is performed in which an amino acid mixed solution containing amino acids is prepared.

[0014] In the first step S100, the amino acids may be L-amino acids or may be prepared by extraction, synthesis, fermentation, enzymatic methods, or the like. In some cases, the amino acids may be obtained from a fermentation product prepared by fermentation using microorganisms. Here, the term "fermentation product" in this application refers to the result of enzymatic or metabolic synthesis or decomposition of organic substances using microorganisms. Examples include a culture containing microorganisms obtained by culturing microorganisms in a culture medium, and a concentrate, dried product, or lyophilized product of the culture obtained by removing the microorganisms from the culture. The amino acid mixture solution here may contain L-amino acids and the entire fermentation product, or may be a fermentation product from which impurities have been removed.

[0015] The fermentation product prepared in the first step S100 to obtain amino acids may be a product obtained by culturing microorganisms that produce L-amino acids. Here, the term "microorganisms that produce L-amino acids" as used herein includes both wild-type microorganisms and naturally or artificially genetically modified microorganisms, and refers to microorganisms that have been genetically modified to produce a desired protein or product, such as microorganisms in which a specific mechanism has been weakened or strengthened by inserting an exogenous gene or by strengthening or inactivating the activity of an endogenous gene.

[0016] The microorganism used in the first step S100 may be at least one selected from microorganisms of the genus Brevibacterium, Corynebacterium, Escherichia, Serratia, Erwinia, Enterobacteria, Streptomyces, Pseudomonas, etc., or artificial mutants thereof. Therefore, the first step S100 may further include a step of preparing an amino acid mixture solution using at least one of the microorganisms described above.

[0017] Among the microorganisms described above in the present application that are used in the first step S100, the "microorganisms of the genus Corynebacterium" include all microorganisms of the genus Corynebacterium. Specifically, Corynebacterium glutamicum, Corynebacterium crudilactis, Corynebacterium deserti, Corynebacterium efficiens, Corynebacterium callunae, Corynebacterium stationis, Corynebacterium singulare, Corynebacterium halotolerans, Corynebacterium striatum, Corynebacterium ammoniagenes, Corynebacterium ammoniagenes, Corynebacterium pollutisoli, Corynebacterium imitans, Corynebacterium testudinoris or Corynebacterium flavescens, and more specifically, Corynebacterium glutamicum, but is not limited to these.

[0018] Microorganisms of the genus Corynebacterium, particularly Corynebacterium glutamicum, are Gram-positive microorganisms that are widely used for the production of L-amino acids and other useful substances. To produce these L-amino acids and other useful substances, various research efforts have been conducted to develop highly efficient production microorganisms and fermentation process technologies. For example, target-specific approaches such as increasing the expression of genes encoding enzymes involved in the biosynthesis of L-tryptophan, L-valine, L-threonine, L-isoleucine, and L-leucine, and deleting genes unnecessary for biosynthesis, have been primarily used.

[0019] In the first step S100, after producing a fermented product containing L-amino acids using the microorganisms described above, a step of separating and purifying the fermented product to recover a mixed amino acid solution may be further carried out. The mixed amino acid solution may be collected using a suitable method known in the art, depending on the culture method of the microorganisms of the present application, such as batch, continuous, or fed-batch culture. For this purpose, the mixed amino acid solution containing the target L-amino acids may be collected using a suitable method known in the art, such as centrifugation, filtration, crystallization, treatment with a protein precipitant (salting out), extraction, ultrasonic disruption, ultrafiltration, dialysis, various types of chromatography such as molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, and affinity chromatography, HPLC, or a combination thereof. The mixed amino acid solution of interest can be recovered from the medium or the microorganisms using a suitable method known in the art.

[0020] In the first step S100, recovering a mixed amino acid solution from the fermented product does not necessarily mean separating and recovering only the L-amino acids contained in the fermentation liquid. Depending on the need, it may mean recovering the entire fermented product, or it may mean recovering a mixed amino acid solution containing L-amino acids from which only some impurities have been removed, or the microorganisms used for the culture.

[0021] The mixed amino acid solution obtained in the first step S100 may further contain any suitable excipient commonly used in compositions for amino acid production, including, but not limited to, preservatives, wetting agents, dispersing agents, suspending agents, buffers, stabilizers, and isotonicity agents.

[0022] After the first step S100 and before the second step S200, a step of concentrating the amino acid mixture solution may be performed. Any concentrating device may be used for the concentrating step. For example, a forced circulation concentrator, a paddle dryer, a slurry dryer, or the like may be used for the concentrating step, but is not limited to these.

[0023] Next, in the second step S200, the amino acid mixed solution is stirred using a thin film dryer to form a thin film, and the formed thin film is dried and pulverized to produce wet granules. The thin film dryer is a device that dries a fluid while stirring it, and may operate in a manner that stirs the fluid that has flowed into a chamber to form a thin film made of the fluid on the wall of the chamber, and then dries the formed thin film. The dried thin film may also be pulverized again into granules and discharged outside the thin film dryer. The thin film dryer may be of any type, including a horizontal type in which the chamber is parallel to the ground, or a vertical type in which the chamber is perpendicular to the ground.

[0024] In the second step S200, at least a portion of the water contained in the mixed amino acid solution may be evaporated and removed. When the mixed amino acid solution is dried in this manner, the solids concentration in the mixed amino acid solution increases, and wet granules are obtained.

[0025] The term "granules" in the wet granules prepared in the second step S200 refers to macroscopic particles that are relatively large permanent aggregates formed by the aggregation of small particles such as powder, and are distinct from the smaller particles that make up the aggregates. When the powder aggregates, it forms particles 30 to 150 times larger than its original size, which can be granulated by re-drying. The particles formed by the granulation process have a porous structure, which makes them wettable and allows for a high dispersion and sedimentation rate in water. In the present application, the term "granulation" refers to, but is not limited to, the process of granulating the fermented product by drying it. The term "wet granules" refers to the state in which moisture remains despite the granular form described above.

[0026] In the second step S200, the water is removed so that the solid content of the mixed amino acid solution falls within a granulation concentration range, which means a solid content range that allows the mixed amino acid solution to be prepared in the form of a granule in the subsequent third step S300.

[0027] In the second step S200, the aforementioned range of granule formation concentration may be varied depending on the type of amino acid. Specifically, the amino acid includes at least one selected from the group consisting of L-threonine, L-tryptophan, L-valine, L-isoleucine, and L-leucine. The range of granule formation concentration may be varied depending on the type and composition of the amino acids contained in the amino acid mixture solution. More specifically, when the amino acid is L-tryptophan, the range of granule formation concentration may be approximately 80% to approximately 92% by weight. When the amino acid is L-valine, the range of granule formation concentration may be approximately 80% to approximately 94% by weight. When the amino acid is L-threonine, the range of granule formation concentration may be approximately 85% to approximately 96% by weight. When the amino acid is L-isoleucine, the range of granule formation concentration may be approximately 82% to approximately 94% by weight. When the amino acid is L-leucine, the range of granule formation concentration may be approximately 82% to approximately 93% by weight. When a plurality of types of amino acids are mixed in the amino acid solution, the range of the granule-forming concentration may be adjusted taking into consideration the types of amino acids mixed and the content of each amino acid.

[0028] Therefore, when performing the second step S200, the range of the granule formation concentration may be controlled based on information about the type and composition of amino acids contained in the amino acid mixture solution obtained in the first step S100. In the second step S200, the drying process may be performed within the determined range of the granule formation concentration.

[0029] In the second step S200, moisture-removed wet granules are obtained, thereby reducing the amount of steam used in the third step S300. To granulate a fermented product, all moisture in the fermented product must be evaporated before granulation. However, in conventional techniques, a portion of the moisture contained in the fermented product is removed by a concentration step before the granulation step. Specifically, in conventional granule production methods, the solids content of the slurry must be adjusted to approximately 40-55% for highly soluble amino acids, and to approximately 18-22% for less soluble amino acids. In the present application, the amino acid mixture solution is dried to a concentration within the granule-forming concentration range in the second step S200. This reduces the amount of steam used in the subsequent third step S300, significantly improving the overall productivity and efficiency of the production process.

[0030] In the second step S200, the linear velocity at which the amino acid mixed solution is stirred may be about 4 m / s to about 17 m / s, about 4 m / s to about 16 m / s, about 4 m / s to about 15 m / s, about 4 m / s to about 14 m / s, about 5 m / s to about 17 m / s, about 5 m / s to about 16 m / s, about 5 m / s to about 15 m / s, or about 5 m / s to about 14 m / s. When the linear velocity at which the amino acid mixed solution is stirred is less than the above range, the thin film formation rate obtained from the amino acid mixed solution in the thin film drying apparatus where the second step S200 is performed is improved, and drying and stirring can be performed without placing a load on the mixer during drying. Furthermore, since the amino acid mixed solution can be dried to an appropriate level without over-drying, a particle size that will not be lost in a bag filter can be obtained, thereby improving the granule recovery rate.

[0031] The second step S200 may be performed at a pressure of about 0.05 to about 0.6 atmospheres, about 0.05 to about 0.5 atmospheres, or about 0.05 to about 0.4 atmospheres. As described above, the second step S200 is performed under a relatively low pressure, which reduces the vapor pressure of the water contained in the amino acid mixture solution and evaporates the water at temperatures below 100°C. Therefore, high temperatures are not required to remove the water in the second step S200, and substances contained in the amino acid mixture solution, such as L-amino acids and microorganisms, are not likely to be denatured during the heating process for drying the water. However, if the pressure for performing the second step S200 is lower than the above range, dust may get into the bag filter of the thin-film drying device, resulting in a reduced yield. Furthermore, if the pressure for performing the second step S200 is higher than the above range, high temperatures are required to dry the water, which may cause browning of the granules due to the high temperature. Furthermore, the drying process requires relatively little heat, resulting in low energy consumption. Therefore, by maintaining the pressure for the second step S200 within the above range, granules can be produced in high yield without denaturing the L-amino acids or the microorganisms.

[0032] The distance between the inner wall surface and the stirring section may be about 5 mm to about 15 mm. Within this range, granule formation is carried out efficiently.

[0033] The particle size of the wet granular particles obtained in the second step S200 is, but is not limited to, 5.0% or less, specifically 3.0% or less, more specifically 1.0% or less of particles 2000 μm or larger, and 20.0% or less, specifically 15.0% or less, more specifically 5.0% or less of particles 75 μm or smaller.

[0034] Next, a third step S300 may be performed in which the wet granules produced in the second step S200 are dried to produce a granular dosage form of an amino acid mixture solid. The third step S300 may be performed using a fluidized bed granulator / dryer. The wet granules may be fed into the fluidized bed granulator / dryer and dried by air flow to produce a granular dosage form of an amino acid mixture solid. However, the third step S300 does not necessarily require the use of only a fluidized bed granulator / dryer.

[0035] The third step S300 may further include a step of sieving the dried granular amino acid mixture solid. Here, the granular amino acid mixture solid may be sieved based on a desired particle size. The particle size used as the basis for sieving is appropriately selected by those skilled in the art. For example, the particle size used as the basis for sieving is about 50 μm to about 3000 μm, specifically about 75 μm to about 2000 μm, and more specifically about 100 μm to about 2000 μm, but is not limited thereto.

[0036] After the third step S300, a process of crushing and / or recycling granule particles not having the desired particle size may be further performed in order to reuse the particles remaining after sieving, as described above. For example, the particles remaining after sieving may have a particle size of 2000 μm or more of 1.0% or less of the total particles, and may have a particle size of 75 μm or less of 1.5% or less of the total particles, but this is not necessarily limited to this.

[0037] The method for pulverizing and / or circulating the granular particles is not particularly limited, and any method known in the art can be used.

[0038] FIG. 2 is a flowchart showing a method for producing a solid amino acid mixture according to the present application.

[0039] As shown in FIG. 2, a step S250 of preparing granules using a mixing-type granulator may be further carried out between the second step S200 and the third step S300.

[0040] In step S250 using a mixing-type granulator, at least a portion of the wet granules prepared in the second step S200 may be used as seeds for preparing granules in the mixing-type granulator. In the mixing-type granulator, the amino acid mixed solution prepared in the first step S100 may be sprayed onto the wet granules prepared by pulverization in the second step S200. This allows granules of appropriate size to be prepared. The granules prepared in the mixing-type granulator may be dried in the third step S300. This produces a granular dosage form of an amino acid mixed solid.

[0041] The method for producing an amino acid mixture solid according to the present invention has been described above. The production apparatus according to the present invention used in the above-described method for producing an amino acid mixture solid will now be described in more detail.

[0042] FIG. 3 is a diagram showing a thin film drying apparatus according to the present application.

[0043] As shown in FIG. 3, the apparatus for producing an amino acid mixed solid includes a fermenter that produces an amino acid mixed solution by a fermentation process, a thin film dryer that dries and pulverizes the amino acid mixed solution supplied from the fermenter to produce wet granules, and a granule dryer that dries the wet granules to produce an amino acid mixed solid in granular dosage form.

[0044] First, a fermenter is a component for obtaining a fermented product containing amino acids by a fermentation method using microorganisms. In the explanation of the fermenter, the microorganisms, the fermentation method, the amino acids, and the fermented product are as described above.

[0045] The fermenter may include a container in which fermentation takes place, an input section for inputting raw materials, a discharge section for discharging the fermented product to the outside after fermentation is completed, a stirring means for stirring the raw materials inside the container, and a heating means for applying heat to cause a fermentation reaction.

[0046] The fermenter may further be provided with a component inside or outside the vessel for collecting an amino acid mixture solution containing L-amino acids from the fermented product. For example, the fermenter may be provided with a component inside or outside the vessel for performing centrifugation, filtration, crystallization, treatment with a protein precipitant (salting out), extraction, ultrasonic disruption, ultrafiltration, dialysis, various types of chromatography such as molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, and affinity chromatography, and HPLC.

[0047] The amino acid mixture solution recovered from the fermented product produced in the fermenter is transferred to a thin-film dryer. Before transferring the fermented product from the fermenter to the thin-film dryer, the amino acid mixture solution may be concentrated using a concentrator. Any concentrator may be used. For example, a forced circulation concentrator may be used, or a paddle dryer, a slurry dryer, or the like may be used in the concentration step, but is not limited thereto.

[0048] The amino acid mixed solution supplied from the fermenter may be dried and pulverized in a thin film dryer to produce wet granules. The thin film dryer simultaneously injects the amino acid mixed solution in a liquid or slurry state into the interior of the device and stirs it, so that a thin film of the amino acid mixed solution is formed on the inner wall of the device. The inner wall is heated to dry the thin film formed on the inner wall. The dried thin film is pulverized to produce wet granules.

[0049] The thin film drying apparatus may be installed horizontally, i.e., parallel to the ground, or vertically, i.e., perpendicular to the ground. The drawings show a horizontal thin film drying apparatus parallel to the ground, but a vertical thin film drying apparatus may also be used if necessary. The aspect ratio of the thin film drying apparatus may also vary depending on the type of thin film drying apparatus used. For example, when the thin film drying apparatus is installed horizontally, i.e., parallel to the ground, the horizontal length (parallel to the ground) may be greater than the vertical length (perpendicular to the ground). Conversely, when the thin film drying apparatus is installed vertically, i.e., perpendicular to the ground, the horizontal length may be smaller than the vertical length. The configuration of such a thin film drying apparatus may vary depending on the type of thin film drying apparatus used and its intended use.

[0050] The thin film drying apparatus includes a thin film drying apparatus stirring section and a heating section.

[0051] The agitation unit of the thin film drying device agitates the amino acid mixed solution that has flowed into the thin film drying device. The amino acid mixed solution agitated by the agitation unit of the thin film drying device is applied to the inner wall of the thin film drying device by centrifugal force and forms a thin film on the inner wall.

[0052] The thin film formed by stirring in the stirring section of the thin film drying device is dried on the inner wall. Specifically, the thin film may be dried on the inner wall by a heating section that transfers heat to the inner wall.

[0053] The thin film dryer agitator may further include a plurality of thin film dryer agitator blades.

[0054] The agitator blade of the thin film dryer may be configured to press the amino acid mixed solution that has flowed into the thin film dryer against the inner wall to form a thin film, and to separate or pulverize the dried thin film from the inner wall. Specifically, the agitator blade of the thin film dryer located adjacent to the inlet (area where the amino acid mixed solution is supplied) of the thin film dryer may be used to press the amino acid mixed solution against the inner wall to form a thin film, and the agitator blade of the thin film dryer located adjacent to the outlet (area where the wet granules are discharged) of the thin film dryer may be used to separate and pulverize the dried thin film from the inner wall to form wet granules.

[0055] The thin film drying device agitator (thin film drying device agitator blade) may be provided at a distance of 5 mm to 15 mm from the inner wall of the thin film drying device. By separating the agitator blade from the inner wall of the thin film drying device within this range, the efficiency of heat transfer to the amino acid mixture solution can be improved and the load on the motor due to agitation can be reduced.

[0056] The heating unit may take any form. The heating unit may be an electric heating element in contact with the inner wall, or may be provided in the form of a tube in contact with the inner wall, and heat may be transferred to the inner wall by supplying steam to the tube. The heating unit may be provided over the entire inner wall of the thin film drying device. In this way, the amino acid mixed solution or thin film can be dried simultaneously over a wide area, improving drying efficiency.

[0057] Next, the wet granules produced in the thin film dryer are supplied to a granule dryer. In the granule dryer, the wet granules are dried to a desired humidity level to produce a granular dosage form of an amino acid mixture solid. The granule dryer may, for example, supply dry hot air to dry the wet granules. However, the provision and operation of the granule dryer are not limited to the above example.

[0058] 4 and 5 are simplified block diagrams showing an apparatus for producing an amino acid mixed solid according to one embodiment of the present application.

[0059] As shown in Figure 4, the apparatus for producing an amino acid mixed solid according to the present application may include the above-mentioned fermenter, a thin film dryer, and a granule dryer. Specifically, the apparatus for producing an amino acid mixed solid according to one embodiment of the present application includes a fermenter that produces an amino acid mixed solution by a fermentation process, a thin film dryer that dries and pulverizes the amino acid mixed solution supplied from the fermenter to prepare wet granules, and a granule dryer that dries the wet granules to produce an amino acid mixed solid in granule dosage form. The thin film dryer may include a thin film dryer stirring unit that stirs the amino acid mixed solution to form a thin film obtained from the amino acid mixed solution on the inner wall of the thin film dryer, and a heating unit that heats the inner wall of the thin film dryer to dry the thin film.

[0060] As shown in Figure 5, the apparatus for producing an amino acid mixed solid further includes a mixing-type granulator. By using the mixing-type granulator, granules can be produced using at least a portion of the wet granules produced in the thin film drying apparatus as seeds. [Effects of the Invention]

[0061] According to the present invention, the amino acid mixture solution is dried to a granule-forming concentration range and then granules are formed, which overcomes the problem of dosage form due to moisture in the conventional tableting method, and can increase production volume and improve process efficiency, thereby significantly contributing to cost reduction in the production of amino acid granules. [Brief explanation of the drawings]

[0062] [Figure 1] 1 is a flowchart showing a method for producing an amino acid mixture solid product according to the present application. [Figure 2] 1 is a flowchart showing a method for producing an amino acid mixture solid product according to the present application. [Figure 3] 1 is a simplified cross-sectional view of a thin film drying apparatus according to the present application. [Figure 4] 1 is a simplified block diagram showing a method and apparatus for producing an amino acid mixture solid according to one embodiment of the present application. [Figure 5]1 is a simplified block diagram showing a method and apparatus for producing an amino acid mixture solid according to one embodiment of the present application. DETAILED DESCRIPTION OF THE INVENTION

[0063] The present application will be described in more detail below with reference to examples. However, these examples are merely preferred embodiments illustrating the present application, and the present application is not limited thereto. Note that technical matters not described in this specification are well understood and easily implemented by skilled artisans in the technical field of the present application or a similar technical field.

[0064] "Example 1A" Production of a solid mixture of amino acids containing L-tryptophan To produce a solid amino acid mixture containing L-tryptophan by the method of the present invention, the L-tryptophan fermentation broth was first collected from the fermenter.

[0065] The recovered L-tryptophan fermentation broth had an L-tryptophan concentration of 57 g / L, a purity of 67%, and a solids content of 8.4%. The recovered L-tryptophan fermentation broth was placed in a pilot concentration tube (forced circulation, Manmin Machinery, Korea) and concentrated. The total 750 L of fermentation broth used for concentration was concentrated five times, with 150 L per concentration depending on the capacity of the concentration tube. The concentration conditions were a pressure of 0.1 atm and a steam pressure of 3 atm, and the broth was concentrated until the solids concentration reached 25.5%. Because gelation and loss of fluidity occurred above 25.5%, concentration was terminated when the solids concentration reached 25.5%. The recovered concentrate had a concentration of 178.9 g / L, a purity of 67%, a solids concentration of 25.5%, and a volume of 239 L. 19.1 L of the recovered concentrate was fed to a thin-film dryer.

[0066] Drying and formulation processes were carried out using a thin film dryer (double jacket, horizontal type, manufactured by Changwoo Machinery Co., Ltd., Korea) to prepare wet granules. In Example 1A, the operating conditions of the thin film dryer were set as follows: internal pressure 0.2 atmospheres, steam pressure 3 atmospheres, knife linear velocity 8 m / s, and gap between the stirring blade and the inner wall of the thin film dryer 5 mm.

[0067] 5.48 kg of wet granules were recovered from the thin film dryer. The recovered wet granules had a purity of 67%, a solid content of 92%, and an average particle size of 400-700 μm. These were placed in a fluidized bed granulator / dryer (GR Engineering Co., Ltd.) and dried. 5.04 kg of mixed amino acid solids were recovered from the fluidized bed granulator / dryer, with a recovery rate of 97.7%, a purity of 67%, and a solid content of 99%.

[0068] Experimental Example 1-1. Comparison of the results of amino acid mixed solid production depending on the solid content in the wet granules recovered from the thin film dryer In order to compare the results of amino acid mixed solid product production depending on the solid content in the wet granules recovered from the thin film dryer, amino acid mixed solid products were produced with varying degrees of moisture drying.

[0069] In the examples and comparative examples used in Experimental Example 1-1, 19.1 L of the same material as the concentrated L-tryptophan fermentation broth in Example 1A was used and supplied to a thin film dryer. The operating conditions of the thin film dryer were the same as in Example 1A, and the feeding rate was adjusted. Next, the wet granules collected in the examples and comparative examples were fed into a fluidized bed granulator / dryer and dried.

[0070] Table 1 shows the experimental results under each condition in the examples and comparative examples.

[0071] [Table 1]

[0072] Experimental results showed that granules could not be formed if the solids content of the wet granules recovered from the thin film dryer was less than 80%, for example, 75% or less. Furthermore, the higher the solids content in the wet granules, the more difficult it became to form granules, requiring an additional formulation process. It was also found that granules could not be formed if the solids content in the wet granules was more than 92%, for example, 96% or more.

[0073] Experimental Example 1-2. Comparison of the results of amino acid mixed solid production depending on the linear stirring speed of the thin film dryer In the Examples and Comparative Examples used in Experimental Examples 1-2, 19.1 L of the same material as the concentrated L-tryptophan fermentation broth in Example 1A was used and supplied to a thin film dryer (Changwoo Machinery, Horizontal type TFD). The stirring speed (linear velocity) in the thin film dryer was adjusted, and the operating conditions of the thin film dryer, except for the stirring speed, were the same as in Example 1A. Next, the wet granules collected in the Examples and Comparative Examples were placed in a fluidized bed granulator / dryer and dried.

[0074] Table 2 shows the experimental results under each condition in the examples and comparative examples.

[0075] [Table 2]

[0076] Experimental results confirmed that the higher the agitation speed (linear velocity) in the thin-film dryer, the greater the heat received by the solids in the amino acid mixture solution, resulting in a higher drying rate. However, when the linear velocity exceeded 17 m / s, the amino acid mixture solution was overdried, reducing the average particle size of the wet granules. This resulted in increased fine powder loss through the bag filters of the thin-film dryer and fluidized bed granulator / dryer, resulting in a lower recovery rate. On the other hand, when the linear velocity was less than 4 m / s, the thin-film formation rate inside the thin-film dryer decreased, and the load on the agitator of the thin-film dryer during drying increased, preventing agitation.

[0077] Experimental Example 1-3. Comparison of the results of amino acid mixed solid production depending on the gap between the agitator and the inner wall of the thin film dryer In the Examples and Comparative Examples used in Experimental Examples 1-3, 19.1 L of the same material as the concentrated L-tryptophan fermentation broth in Example 1A was used and supplied to the thin film dryer. The distance between the agitator blade and the inner wall of the thin film dryer was adjusted, and the other operating conditions of the thin film dryer were the same as in Example 1A. Next, the wet granules collected in the Examples and Comparative Examples were placed in a fluidized bed granulator / dryer and dried.

[0078] Table 3 shows the experimental results under each condition in the examples and comparative examples.

[0079] [Table 3]

[0080] The experimental results showed that the wider the gap between the inner wall of the thin film dryer and the agitator blade of the thin film dryer, the larger the amount of material to be dried, and the slower the heat transfer, resulting in a corresponding decrease in the drying rate. Furthermore, when the gap exceeded approximately 15 mm, as in Comparative Example 1E, the load on the agitator motor of the thin film dryer increased due to the material to be dried, making operation impossible.

[0081] Experimental Example 1-4. Comparison of amino acid mixed solid production results depending on pressure conditions in the thin film dryer In the Examples and Comparative Examples used in Experimental Examples 1-4, 19.1 L of the same material as the concentrated L-tryptophan fermentation broth in Example 1A was used and supplied to the thin film dryer. The internal pressure of the thin film dryer was adjusted, and the operating conditions of the thin film dryer, excluding the internal pressure, were the same as in Example 1A. Next, the wet granules collected in the Examples and Comparative Examples were loaded into a fluidized bed granulator / dryer and dried.

[0082] Table 4 shows the experimental results under each condition in the examples and comparative examples.

[0083] [Table 4]

[0084] The experimental results showed that as the pressure inside the thin film dryer decreased, dust got into the bag filter, reducing the process yield, whereas when the pressure inside the thin film dryer was high, the moisture drying was carried out at a relatively high temperature, causing browning due to the high temperature. Specifically, when the pressure inside the thin film dryer exceeded approximately 0.05 atmospheres (Comparative Example 1F), browning was observed in the produced amino acid mixture solid. Furthermore, when the pressure inside the thin film dryer was less than approximately 0.6 atmospheres (Comparative Example 1G), dust got into the bag filter of the thin film dryer, reducing the process yield to approximately 91.6%.

[0085] Experimental Example 1-5. Preparation of granules using a thin film dryer and a mixer-type granulator Granules were formed using the L-tryptophan concentrate recovered in Example 1A using a thin film dryer and a mixer-type granulator.

[0086] In Example 1J, 18.5 L of the 19.1 L of L-tryptophan concentrate recovered in Example 1A was loaded into a thin-film dryer (Changwoo Machinery, Horizontal type TFD) and dried. The operating conditions of the thin-film dryer were the same as in Example 1A, except that the concentrate loading rate was slower. The discharged dried material was 5.03 kg, had a purity of 67%, a solids content of 96%, and an average particle size of 200-300 μm. The discharged dried material was loaded into a mixer granulator (Lodige, Mix-Granulator) as seeds, and the remaining 0.6 L of L-tryptophan concentrate was loaded into the mixer granulator using a metering pump (EYELA, RP-2100). The wet granules produced in the mixer granulator were 5.68 kg, had a purity of 67%, and a solids content of 88%. The granules were then loaded into a laboratory fluidized-bed granulator / dryer and dried. The recovery rate was 96.6%, with 4.98 kg recovered. The purity was 67% and the solid content was 99%.

[0087] Next, in Comparative Example 1H, 1.6 L of the L-tryptophan concentrate recovered in Example 1A and 9.5 kg of seeds (purity 65%, solids content 99%, average particle size 200-300 μm) were directly charged into a mixer-type granulator (Lodige, Mix-Granulator) rather than a thin-film dryer to prepare wet granules. The L-tryptophan concentrate was charged into the mixer-type granulator using a metering pump (EYELA, RP-2100). The resulting wet granules were 11.15 kg, with a purity of 65.1% and a solids content of 88%. The prepared wet granules were then charged into a laboratory fluidized-bed granulator / dryer and dried. 9.79 kg was recovered at a recovery rate of 98.8%. The purity was 65.1% and the solids content was 99%.

[0088] Example 1J confirmed that a concentrated solution with a high moisture content can be made into fine granules using a thin film dryer and can be used as seeds for a mixing type granulator.

[0089] "Example 2A" Manufacturing of a solid mixture of amino acids containing L-valine To produce a solid amino acid mixture containing L-valine by the method of the present invention, the L-valine fermentation broth was first recovered from the fermenter.

[0090] The recovered L-valine fermentation broth had an L-valine concentration of 80 g / L, a purity of 80%, and a solids content of 9.8%. The recovered L-valine fermentation broth was placed in a pilot concentration tube (forced circulation, Manmin Machinery Co., Ltd., Korea) and concentrated. The total 900 L of fermentation broth used for concentration was concentrated six times, with 150 L per concentration depending on the capacity of the concentration tube. The concentration conditions were a pressure of 0.1 atm and a steam pressure of 3 atm, and the broth was concentrated until the solids concentration reached 28%. Because gelation and loss of fluidity occurred above 28%, concentration was terminated when the solids concentration reached 28%. The recovered concentrate had a concentration of 237.3 g / L, a purity of 80%, a solids concentration of 28%, and a volume of 303.4 L. 20.2 L of the recovered concentrate was fed to a thin-film dryer.

[0091] Drying and formulation processes were carried out using a thin film dryer (double jacket, horizontal type, manufactured by Changwoo Machinery Co., Ltd., Korea) to prepare wet granules. The operating conditions of the thin film dryer were set to the same as those in Example 1A.

[0092] 6.58 kg of wet granules were recovered from the thin film dryer. The recovered wet granules had a purity of 80%, a solid content of 90%, and an average particle size of 400-700 μm. These were placed in a fluidized bed granulator / dryer (GR Engineering Co., Ltd.) and dried. 5.92 kg of amino acid mixture solids were recovered from the fluidized bed granulator / dryer, with a recovery rate of 97.7%, a purity of 80%, and a solid content of 99%.

[0093] Experimental Example 2-1. Comparison of the results of amino acid mixed solid production depending on the solid content of the wet granules recovered from the thin film dryer In order to compare the results of amino acid mixed solid product production depending on the solid content in the wet granules recovered from the thin film dryer, amino acid mixed solid products were produced with varying degrees of moisture drying.

[0094] In the examples and comparative examples used in Experimental Example 2-1, 20.2 L of the same material as the concentrated L-valine fermentation broth in Example 2A was used and supplied to the thin film dryer. The operating conditions of the thin film dryer were the same as in Example 2A, and the feeding rate was adjusted. Next, the wet granules collected in the examples and comparative examples were fed into a fluidized bed granulator / dryer and dried.

[0095] Table 5 shows the experimental results under each condition in the examples and comparative examples.

[0096] [Table 5]

[0097] As a result of the experiment, it was confirmed that granules were not formed when the solid content of the wet granules recovered from the thin film dryer was less than 80% (Comparative Example 2A). Furthermore, as the solid content of the wet granules increased, granule formation became more difficult, requiring an additional formulation step. When the solid content of the wet granules exceeded 94% (Comparative Example 2B), granules were not formed.

[0098] Experimental Example 2-2. Comparison of the results of amino acid mixed solid production depending on the linear stirring speed of the thin film dryer In the examples and comparative examples used in Experimental Example 2-2, 20.2 L of the same material as the concentrated L-valine fermentation broth in Example 2A was used and supplied to a thin film dryer (Changwoo Machinery, Horizontal type TFD). The stirring speed (linear velocity) in the thin film dryer was adjusted, and the operating conditions of the thin film dryer, except for the stirring speed, were the same as in Example 2A. Next, the wet granules collected in the examples and comparative examples were placed in a fluidized bed granulator / dryer and dried.

[0099] Table 6 shows the experimental results under each condition in the examples and comparative examples.

[0100] [Table 6]

[0101] Experimental results confirmed that the higher the agitation speed (linear velocity) in the thin-film dryer, the greater the heat received by the solids in the amino acid mixture solution, resulting in a higher drying rate. However, when the linear velocity exceeded 17 m / s, the amino acid mixture solution was overdried, reducing the average particle size of the wet granules. This resulted in increased fine powder loss through the bag filters of the thin-film dryer and fluidized bed granulator / dryer, resulting in a lower recovery rate. On the other hand, when the linear velocity was less than 4 m / s, the thin-film formation rate inside the thin-film dryer decreased, and the load on the agitator of the thin-film dryer during drying increased, preventing agitation.

[0102] Experimental Example 2-3. Comparison of amino acid mixed solid production results depending on pressure conditions in the thin film dryer In the examples and comparative examples used in Experimental Examples 2-3, 20.2 L of the same material as the concentrated L-valine fermentation broth in Example 2A was used and supplied to the thin film dryer. The internal pressure of the thin film dryer was adjusted, and the operating conditions of the thin film dryer, excluding the internal pressure, were the same as in Example 2A. Next, the wet granules collected in the examples and comparative examples were placed in a fluidized bed granulator / dryer and dried.

[0103] Table 7 shows the experimental results under each condition in the examples and comparative examples.

[0104] [Table 7]

[0105] The experimental results showed that as the pressure inside the thin film dryer decreased, dust got into the bag filter, reducing the process yield, whereas when the pressure inside the thin film dryer was high, the moisture drying was performed at a relatively high temperature, causing browning due to the high temperature. Specifically, when the pressure inside the thin film dryer exceeded approximately 0.05 atmospheres (Comparative Example 2E), browning was observed in the produced amino acid mixture solid. Furthermore, when the pressure inside the thin film dryer was less than approximately 0.6 atmospheres (Comparative Example 2F), dust got into the bag filter of the thin film dryer, reducing the process yield to approximately 90.5%.

[0106] Experimental Example 2-4. Granule production using a thin film dryer and a mixed granulator The L-valine concentrate recovered in Example 2A was used to form granules using a thin film dryer and a mixing granulator.

[0107] In Example 2H, 19.4 L of the 20.2 L of L-valine concentrate recovered in Example 2A was loaded into a thin-film dryer (Changwoo Machinery, Horizontal type TFD) and dried. The operating conditions of the thin-film dryer were the same as in Example 2A, except that the concentrate loading rate was slower. The discharged dried material was 5.93 kg, had a purity of 80%, a solids content of 95%, and an average particle size of 200-300 μm. The discharged dried material was loaded into a mixer-type granulator (Lodige, Mix-Granulator) as seeds, and the remaining 0.9 L of L-valine concentrate was loaded into the mixer-type granulator using a metering pump (EYELA, RP-2100). The wet granules produced in the mixer-type granulator were 6.85 kg, had a purity of 80%, and a solids content of 86%. The granules were then loaded into a laboratory fluidized-bed granulator / dryer and dried. The recovery rate was 96.7%, with 5.86 kg recovered. The purity was 80% and the solid content was 99%.

[0108] Next, in Comparative Example 2G, 1.7 L of the L-valine concentrate recovered in Example 2A and 8.0 kg of seeds (78% purity, 99% solids, average particle size 200-300 μm) were directly charged into a mixer-type granulator (Lodige, Mix-Granulator) rather than a thin-film dryer to prepare wet granules. The L-valine concentrate was fed into the mixer-type granulator using a metering pump (EYELA, RP-2100). The resulting wet granules were 9.75 kg, with a purity of 78.1% and a solids content of 86%. The resulting wet granules were then charged into a laboratory fluidized-bed granulator / dryer and dried. 8.34 kg were recovered at a recovery rate of 98.4%. The purity was 78.1% and the solids content was 99%.

[0109] Example 2H confirmed that a concentrated solution with a high moisture content can be made into fine granules using a thin film dryer and can be used as seeds for a mixing type granulator.

[0110] "Example 3A" Manufacturing of a solid amino acid mixture containing L-threonine To produce a solid amino acid mixture containing L-threonine by the method of the present invention, the L-threonine fermentation broth was first recovered from the fermenter.

[0111] The recovered L-threonine fermentation broth had an L-threonine concentration of 155 g / L, a purity of 85%, and a solids content of 17.7%. The recovered L-threonine fermentation broth was placed in a pilot concentration tube (forced circulation, Manmin Machinery Co., Ltd., Korea) and concentrated. The total 900 L of fermentation broth used for concentration was concentrated six times, with 150 L per concentration depending on the capacity of the concentration tube. The concentration conditions were a pressure of 0.1 atmosphere and a steam pressure of 3 atmospheres, and the broth was concentrated until the solids concentration reached 60%. Because gelation and loss of fluidity occurred at solids concentrations above 60%, concentration was terminated when the solids concentration reached 60%. The recovered concentrate had a concentration of 237.3 g / L, a purity of 85%, a solids concentration of 60%, and a volume of 246.5 L. 16.4 L of the recovered concentrate was fed to a thin-film dryer.

[0112] Drying and formulation processes were carried out using a thin film dryer (double jacket, horizontal type, manufactured by Changwoo Machinery Co., Ltd., Korea) to prepare wet granules. The operating conditions of the thin film dryer were set to the same as those in Example 1A.

[0113] 11.78 kg of wet granules were recovered from the thin film dryer. The recovered wet granules had a purity of 85%, a solid content of 92%, and an average particle size of 300-600 μm. These were placed in a fluidized bed granulator / dryer (GR Engineering Co., Ltd.) and dried. 10.82 kg of mixed amino acid solids were recovered from the fluidized bed granulator / dryer at a recovery rate of 97.9%, with a purity of 85% and a solid content of 99%.

[0114] Experimental Example 3-1. Comparison of the results of amino acid mixed solid production depending on the solid content in the wet granules recovered from the thin film dryer In order to compare the results of amino acid mixed solid product production depending on the solid content in the wet granules recovered from the thin film dryer, amino acid mixed solid products were produced with varying degrees of moisture drying.

[0115] In the Examples and Comparative Examples used in Experimental Example 3-1, 16.4 L of the same material as the concentrated L-threonine fermentation broth in Example 3A was used and fed to a thin film dryer. The operating conditions of the thin film dryer were the same as in Example 3A, and the feeding rate was adjusted. Next, the wet granules collected in the Examples and Comparative Examples were fed to a fluidized bed granulator / dryer and dried.

[0116] Table 8 shows the experimental results under each condition in the examples and comparative examples.

[0117] [Table 8]

[0118] As a result of the experiment, it was confirmed that granules were not formed when the solid content of the wet granules recovered from the thin film dryer was less than 85% (Comparative Example 3A). Furthermore, as the solid content of the wet granules increased, granule formation became more difficult, requiring an additional formulation step. When the solid content of the wet granules exceeded 96% (Comparative Example 3B), granules were not formed.

[0119] Experimental Example 3-2. Comparison of the results of amino acid mixed solid production depending on the linear stirring speed of the thin film dryer In the Examples and Comparative Examples used in Experimental Example 3-2, 16.4 L of the same material as the concentrated L-threonine fermentation broth in Example 3A was used and supplied to a thin film dryer (Changwoo Machinery, Horizontal type TFD). The stirring speed (linear velocity) in the thin film dryer was adjusted, and the operating conditions of the thin film dryer, except for the stirring speed, were the same as in Example 3A. Next, the wet granules collected in the Examples and Comparative Examples were loaded into a fluidized bed granulator / dryer and dried.

[0120] Table 9 shows the experimental results under each condition in the examples and comparative examples.

[0121] [Table 9]

[0122] Experimental results confirmed that the higher the agitation speed (linear velocity) in the thin-film dryer, the greater the heat received by the solids in the amino acid mixture solution, resulting in a higher drying rate. However, when the linear velocity exceeded 17 m / s, the amino acid mixture solution was overdried, reducing the average particle size of the wet granules. This resulted in increased fine powder loss through the bag filters of the thin-film dryer and fluidized bed granulator / dryer, resulting in a lower recovery rate. On the other hand, when the linear velocity was less than 4 m / s, the thin-film formation rate inside the thin-film dryer decreased, and the load on the agitator of the thin-film dryer during drying increased, preventing agitation.

[0123] Experimental Example 3-3. Comparison of amino acid mixed solid production results depending on pressure conditions in the thin film dryer In the examples and comparative examples used in Experimental Example 3-3, 16.4 L of the same material as the concentrated L-threonine fermentation broth in Example 3A was used and supplied to a thin film dryer. The internal pressure of the thin film dryer was adjusted, and the operating conditions of the thin film dryer, excluding the internal pressure, were the same as in Example 3A. Next, the wet granules collected in the examples and comparative examples were loaded into a fluidized bed granulator / dryer and dried.

[0124] Table 10 shows the experimental results under each condition for the examples and comparative examples.

[0125] [Table 10]

[0126] The experimental results showed that as the pressure inside the thin film dryer decreased, dust got into the bag filter, reducing the process yield, whereas when the pressure inside the thin film dryer was high, the moisture drying was performed at a relatively high temperature, causing browning due to the high temperature. Specifically, when the pressure inside the thin film dryer exceeded approximately 0.05 atmospheres (Comparative Example 3E), browning was observed in the produced amino acid mixture solid. Furthermore, when the pressure inside the thin film dryer was less than approximately 0.6 atmospheres (Comparative Example 3F), dust got into the bag filter of the thin film dryer, reducing the process yield to approximately 90.0%.

[0127] Experimental Example 3-4. Granule production using a thin film dryer and a mixed granulator The L-threonine concentrate recovered in Example 3A was used to form granules using a thin film dryer and a mixing granulator.

[0128] In Example 3H, 15.8 L of the 16.4 L of L-threonine concentrate recovered in Example 3A was introduced into a thin-film dryer (Changwoo Machinery, Horizontal type TFD) and dried. The operating conditions of the thin-film dryer were the same as in Example 3A, except that the concentrate introduction rate was slower. The discharged dried material was 10.51 kg, had a purity of 85%, a solids content of 96%, and an average particle size of 200-300 μm. The discharged dried material was introduced into a mixer granulator (Lodige, Mix-Granulator) as seeds, and the remaining 0.9 L of L-threonine concentrate was introduced into the mixer granulator using a metering pump (EYELA, RP-2100). The wet granules produced in the mixer granulator were 11.46 kg, had a purity of 85%, and a solids content of 93%. The resulting granules were then introduced into a laboratory fluidized-bed granulator / dryer for drying. The recovery rate was 96.3%, with 10.64 kg recovered. The purity was 85% and the solid content was 99%.

[0129] Next, in Comparative Example 3G, 1.4 L of the L-threonine concentrate recovered in Example 3A and 8.4 kg of seeds (purity 82.5%, solids content 99%, average particle size 200-300 μm) were directly charged into a mixer granulator (Lodige, Mix-Granulator) rather than a thin-film dryer to prepare wet granules. The resulting wet granules had a weight of 9.88 kg, a purity of 82.7%, and a solids content of 93%. The L-threonine concentrate was charged into the mixer granulator using a metering pump (EYELA, RP-2100). The prepared wet granules were then charged into a laboratory fluidized-bed granulator / dryer and dried. 9.15 kg was recovered at a recovery rate of 98.6%. The purity was 82.7%, and the solids content was 99%.

[0130] Example 3H confirmed that a concentrated solution with a high moisture content can be made into fine granules using a thin film dryer and can be used as seeds for a mixing type granulator.

[0131] Example 4A Manufacturing a solid amino acid mixture containing L-isoleucine To produce a solid amino acid mixture containing L-isoleucine by the method of the present invention, the L-isoleucine fermentation broth was first recovered from the fermenter.

[0132] The recovered L-isoleucine fermentation broth had an L-isoleucine concentration of 36 g / L, a purity of 58%, and a solids content of 6.1%. The recovered L-isoleucine fermentation broth was placed in a pilot concentration tube (forced circulation, Manmin Machinery, Korea) and concentrated. The total 900 L of fermentation broth used for concentration was concentrated six times, with 150 L per concentration depending on the capacity of the concentration tube. The concentration conditions were a pressure of 0.1 atmosphere and a steam pressure of 3 atmospheres, and the broth was concentrated until the solids concentration reached 31%. Because gelation and loss of fluidity occurred at solids concentrations above 31%, concentration was terminated when the solids concentration reached 31%. The recovered concentrate had a concentration of 180.2 g / L, a purity of 58%, a solids concentration of 31%, and a volume of 162.2 L. 10.8 L of the recovered concentrate was fed to a thin-film dryer.

[0133] Drying and formulation processes were carried out using a thin film dryer (double jacket, horizontal type, manufactured by Changwoo Machinery Co., Ltd., Korea) to prepare wet granules. The operating conditions of the thin film dryer were set to the same as those in Example 1A.

[0134] 4.19 kg of wet granules were recovered from the thin film dryer. The recovered wet granules had a purity of 58%, a solid content of 88%, and an average particle size of 400-600 μm. These were placed in a fluidized bed granulator / dryer (GR Engineering Co., Ltd.) and dried. 3.70 kg of mixed amino acid solids were recovered from the fluidized bed granulator / dryer with a recovery rate of 98.3%, and had a purity of 58% and a solid content of 99%.

[0135] Experimental Example 4-1. Comparison of the results of amino acid mixed solid production depending on the solid content of the wet granules recovered from the thin film dryer In order to compare the results of amino acid mixed solid product production depending on the solid content in the wet granules recovered from the thin film dryer, amino acid mixed solid products were produced with varying degrees of moisture drying.

[0136] In the Examples and Comparative Examples used in Experimental Example 4-1, 10.3 L of the same material as the concentrated L-isoleucine fermentation broth in Example 4A was used and supplied to a thin film dryer. The operating conditions of the thin film dryer were the same as in Example 4A, and the feeding rate was adjusted. Next, the wet granules collected in the Examples and Comparative Examples were fed into a fluidized bed granulator / dryer and dried.

[0137] Table 11 shows the experimental results under each condition in the examples and comparative examples.

[0138] [Table 11]

[0139] Experimental results showed that granules were not formed when the solid content of the wet granules recovered from the thin film dryer was less than 82% (Comparative Example 4A). Furthermore, as the solid content of the wet granules increased, granule formation became more difficult, requiring an additional formulation step. Granules were not formed when the solid content of the wet granules exceeded 94% (Comparative Example 4B).

[0140] Experimental Example 4-2. Comparison of the results of amino acid mixed solid production depending on the linear stirring speed of the thin film dryer In the examples and comparative examples used in Experimental Example 4-2, 10.3 L of the same material as the concentrated L-isoleucine fermentation broth in Example 4A was used and supplied to a thin film dryer (Changwoo Machinery, Horizontal type TFD). The stirring speed (linear velocity) in the thin film dryer was adjusted, and the operating conditions of the thin film dryer, except for the stirring speed, were the same as in Example 4A. Next, the wet granules collected in the examples and comparative examples were placed in a fluidized bed granulator / dryer and dried.

[0141] Table 12 shows the experimental results under each condition in the examples and comparative examples.

[0142] [Table 12]

[0143] Experimental results confirmed that the higher the agitation speed (linear velocity) in the thin-film dryer, the greater the heat received by the solids in the amino acid mixture solution, resulting in a higher drying rate. However, when the linear velocity exceeded 17 m / s, the amino acid mixture solution was overdried, reducing the average particle size of the wet granules. This resulted in increased fine powder loss through the bag filters of the thin-film dryer and fluidized bed granulator / dryer, resulting in a lower recovery rate. On the other hand, when the linear velocity was less than 4 m / s, the thin-film formation rate inside the thin-film dryer decreased, and the load on the agitator of the thin-film dryer during drying increased, preventing agitation.

[0144] Experimental Example 4-3. Comparison of amino acid mixed solid production results depending on pressure conditions in the thin film dryer In the examples and comparative examples used in Experimental Example 4-3, 10.3 L of the same material as the concentrated L-isoleucine fermentation broth in Example 4A was used and supplied to the thin film dryer. The internal pressure of the thin film dryer was adjusted, and the operating conditions of the thin film dryer, excluding the internal pressure, were the same as in Example 4A. Next, the wet granules collected in the examples and comparative examples were introduced into a fluidized bed granulator / dryer and dried.

[0145] Table 13 shows the experimental results under each condition for the examples and comparative examples.

[0146] [Table 13]

[0147] The experimental results showed that as the pressure inside the thin film dryer decreased, dust got into the bag filter, reducing the process yield, whereas when the pressure inside the thin film dryer was high, the moisture drying was performed at a relatively high temperature, causing browning due to the high temperature. Specifically, when the pressure inside the thin film dryer exceeded approximately 0.05 atmospheres (Comparative Example 4E), browning was observed in the produced amino acid mixture solid. Furthermore, when the pressure inside the thin film dryer was less than approximately 0.6 atmospheres (Comparative Example 4F), dust got into the bag filter of the thin film dryer, reducing the process yield to approximately 91.1%.

[0148] Experimental Example 4-4. Granule production using a thin film dryer and a mixed granulator The L-isoleucine concentrate recovered in Example 4A was used to form granules using a thin film dryer and a mixing granulator.

[0149] In Example 4H, 10.3 L of the 10.8 L of L-isoleucine concentrate recovered in Example 4A was loaded into a thin-film dryer (Changwoo Machinery, Horizontal type TFD) and dried. The operating conditions of the thin-film dryer were the same as in Example 4A, except that the concentrate loading rate was slower. The discharged dried material was 3.64 kg, had a purity of 58%, a solids content of 95.2%, and an average particle size of 200-300 μm. The discharged dried material was loaded into a mixer granulator (Lodige, Mix-Granulator) as seeds, and the remaining 0.5 L of L-isoleucine concentrate was loaded into the mixer granulator using a metering pump (EYELA, RP-2100). The wet granules produced in the mixer granulator were 4.17 kg, had a purity of 58%, and a solids content of 87%. The granules were then loaded into a laboratory fluidized-bed granulator / dryer for drying. The recovery rate was 96.4%, with a weight of 3.63 kg. The purity was 58% and the solid content was 99%.

[0150] Next, in Comparative Example 4G, 1.8 L of the L-isoleucine concentrate recovered in Example 4A and 13.1 kg of seeds (purity 56.5%, solids content 99%, average particle size 200-300 μm) were directly charged into a mixer-type granulator (Lodige, Mix-Granulator) rather than a thin-film dryer to prepare wet granules. The resulting wet granules had a mass of 15.13 kg, a purity of 56.6%, and a solids content of 90%. The L-isoleucine concentrate was charged into the mixer-type granulator using a metering pump (EYELA, RP-2100). The prepared wet granules were then charged into a laboratory fluidized-bed granulator / dryer and dried. 13.59 kg was recovered at a recovery rate of 98.8%. The purity was 56.6%, and the solids content was 99%.

[0151] Example 4H confirmed that a concentrated solution with a high moisture content can be made into fine granules using a thin film dryer and can be used as seeds for a mixing type granulator.

[0152] "Example 5A" Manufacturing a solid mixture of amino acids containing L-leucine To produce a solid amino acid mixture containing L-leucine by the method of the present invention, the L-leucine fermentation broth was first recovered from the fermenter.

[0153] The recovered L-leucine fermentation broth had an L-leucine concentration of 24 g / L, a purity of 46%, and a solids content of 5.6%. The recovered L-leucine fermentation broth was placed in a pilot concentration tube (forced circulation, Manmin Machinery, Korea) and concentrated. The total 900 L of fermentation broth used for concentration was concentrated six times, with 150 L per concentration depending on the capacity of the concentration tube. The concentration conditions were a pressure of 0.1 atmosphere and a steam pressure of 3 atmospheres, and the broth was concentrated until the solids concentration reached 35%. Because gelation and loss of fluidity occurred when the solids concentration reached 42% or higher, concentration was terminated when the solids concentration reached 35%. The recovered concentrate had a concentration of 151.0 g / L, a purity of 44%, a solids content of 35%, and a volume of 142.2 L. 10.5 L of the recovered concentrate was fed to a thin-film dryer.

[0154] Drying and formulation processes were carried out using a thin film dryer (double jacket, horizontal type, manufactured by Changwoo Machinery Co., Ltd., Korea) to prepare wet granules. The operating conditions of the thin film dryer were set to the same as those in Example 1A.

[0155] 4.12 kg of wet granules were recovered from the thin film dryer. The recovered wet granules had a purity of 43%, a solid content of 87%, and an average particle size of 400-600 μm. These were placed in a fluidized bed granulator / dryer (GR Engineering Co., Ltd.) and dried. 3.60 kg of mixed amino acid solids were recovered from the fluidized bed granulator / dryer with a recovery rate of 97.2%, and had a purity of 43% and a solid content of 99%.

[0156] Experimental Example 5-1. Comparison of the results of amino acid mixed solid production depending on the solid content of the wet granules recovered from the thin film dryer In order to compare the results of amino acid mixed solid product production depending on the solid content in the wet granules recovered from the thin film dryer, amino acid mixed solid products were produced with varying degrees of moisture drying.

[0157] In the examples and comparative examples used in Experimental Example 5-1, 10.0 L of the same material as the concentrated L-leucine fermentation broth in Example 5A was used and supplied to a thin film dryer. The operating conditions of the thin film dryer were the same as in Example 5A, and the feeding rate was adjusted. Next, the wet granules collected in the examples and comparative examples were fed into a fluidized bed granulator / dryer and dried.

[0158] Table 14 shows the experimental results under each condition in the examples and comparative examples.

[0159] [Table 14]

[0160] Experimental results showed that granules were not formed when the solid content of the wet granules recovered from the thin film dryer was less than 82% (Comparative Example 5A). Furthermore, as the solid content of the wet granules increased, granule formation became more difficult, requiring an additional formulation step. Granules were not formed when the solid content of the wet granules exceeded 93% (Comparative Example 2B).

[0161] Experimental Example 5-2. Comparison of the results of amino acid mixed solid production depending on the linear stirring speed of the thin film dryer In the examples and comparative examples used in Experimental Example 5-2, 10.0 L of the same material as the concentrated L-leucine fermentation broth in Example 5A was used and supplied to a thin film dryer (Changwoo Machinery, Horizontal type TFD). The stirring speed (linear velocity) in the thin film dryer was adjusted, and the operating conditions of the thin film dryer, except for the stirring speed, were the same as in Example 5A. Next, the wet granules collected in the examples and comparative examples were placed in a fluidized bed granulator / dryer and dried.

[0162] Table 15 shows the experimental results under each condition for the examples and comparative examples.

[0163] [Table 15]

[0164] Experimental results confirmed that the higher the agitation speed (linear velocity) in the thin-film dryer, the greater the heat received by the solids in the amino acid mixture solution, resulting in a higher drying rate. However, when the linear velocity exceeded 17 m / s, the amino acid mixture solution was overdried, reducing the average particle size of the wet granules. This resulted in increased fine powder loss through the bag filters of the thin-film dryer and fluidized bed granulator / dryer, resulting in a lower recovery rate. On the other hand, when the linear velocity was less than 4 m / s, the thin-film formation rate inside the thin-film dryer decreased, and the load on the agitator of the thin-film dryer during drying increased, preventing agitation.

[0165] Experimental Example 5-3. Comparison of the results of amino acid mixed solid production depending on the pressure conditions in the thin film dryer In the examples and comparative examples used in Experimental Example 5-3, 10.0 L of the same material as the concentrated L-leucine fermentation broth in Example 5A was used and supplied to the thin film dryer. The internal pressure of the thin film dryer was adjusted, and the operating conditions of the thin film dryer, excluding the internal pressure, were the same as in Example 5A. Next, the wet granules collected in the examples and comparative examples were introduced into a fluidized bed granulator / dryer and dried.

[0166] Table 16 shows the experimental results under each condition for the examples and comparative examples.

[0167] [Table 16]

[0168] The experimental results showed that as the pressure inside the thin film dryer decreased, dust got into the bag filter, reducing the process yield, whereas when the pressure inside the thin film dryer was high, the moisture drying was carried out at a relatively high temperature, causing browning due to the high temperature. Specifically, when the pressure inside the thin film dryer exceeded approximately 0.05 atmospheres (Comparative Example 5E), browning was observed in the produced amino acid mixture solid. Furthermore, when the pressure inside the thin film dryer was less than approximately 0.6 atmospheres (Comparative Example 5F), dust got into the bag filter of the thin film dryer, reducing the process yield to approximately 93.1%.

[0169] Experimental Example 5-4. Granule production using a thin film dryer and a mixed granulator The L-leucine concentrate recovered in Example 5A was used to form granules using a thin film dryer and a mixing granulator.

[0170] In Example 5H, 10.0 L of the 10.5 L of L-leucine concentrate recovered in Example 5A was loaded into a thin-film dryer (Changwoo Machinery, Horizontal type TFD) and dried. The operating conditions of the thin-film dryer were the same as in Example 5A, except that the concentrate loading rate was slower. The discharged dried material was 3.69 kg, had a purity of 44%, a solids content of 94.5%, and an average particle size of 200-300 μm. The discharged dried material was loaded into a mixer granulator (Lodige, Mix-Granulator) as seeds, and the remaining 0.5 L of L-leucine concentrate was loaded into the mixer granulator using a metering pump (EYELA, RP-2100). The wet granules produced in the mixer granulator were 4.19 kg, had a purity of 44%, and a solids content of 86%. The granules were then loaded into a laboratory fluidized-bed granulator / dryer and dried. The recovery rate was 96.4%, with a weight of 3.63 kg. The purity was 43% and the solid content was 99%.

[0171] Next, in Comparative Example 5G, 2.0 L of the L-leucine concentrate recovered in Example 5A and 15.3 kg of seeds (purity 43%, solids content 99%, average particle size 200-300 μm) were directly charged into a mixer-type granulator (Lodige, Mix-Granulator) rather than a thin-film dryer to prepare wet granules. The L-leucine concentrate was charged into the mixer-type granulator using a metering pump (EYELA, RP-2100). The resulting wet granules were 18.10 kg, with a purity of 43% and a solids content of 88%. The prepared wet granules were then charged into a laboratory fluidized-bed granulator / dryer and dried. 16.05 kg were recovered at a recovery rate of 98.8%. The purity was 43% and the solids content was 99%.

[0172] Example 5H confirmed that a concentrated solution with a high moisture content can be made into fine granules using a thin film dryer and can be used as seeds for a mixing type granulator.

[0173] From the above description, those skilled in the art to which the present application pertains will understand that the present application can be implemented in other specific forms without changing the technical idea or essential features thereof. It should be understood that the above examples are merely illustrative and not limiting. The present application should be construed as including all modifications and variations derived from the meaning and scope of the claims, rather than the specification, and their equivalent concepts.

[0174] The present disclosure encompasses the following aspects, which correspond respectively to claims 1-13 in the international application. [Appendix 1] A method for producing an amino acid mixed solid, comprising: a first step of preparing an amino acid mixed solution containing amino acids; a second step of stirring the amino acid mixed solution to form a thin film, drying and pulverizing the formed thin film to produce wet granules; and a third step of drying the wet granules to produce an amino acid mixed solid in granule dosage form, wherein in the second step, the amino acid mixed solution is dried so that the solid concentration in the wet granules is within the range of the granule formation concentration. [Appendix 2] A method for producing an amino acid mixed solid described in Appendix 1, further comprising the step of preparing granules using a mixing-type granulator after performing the second step and before performing the third step, and using at least a portion of the wet granules prepared in the second step as seeds for preparing the granules in the mixing-type granulator. [Appendix 3] A method for producing an amino acid mixture solid according to Appendix 1, wherein the range of the granule formation concentration in the second step is controlled depending on the type of amino acid. [Appendix 4] A method for producing a solid amino acid mixture according to Appendix 1, wherein the amino acid comprises at least one selected from the group consisting of L-threonine, L-tryptophan, L-valine, L-isoleucine, and L-leucine. [Appendix 5] The method for producing an amino acid mixture solid according to Appendix 1, wherein the first step comprises producing the amino acid mixture solution by fermentation using at least one microorganism selected from the group consisting of microorganisms of the genus Brevibacterium, Corynebacterium, Escherichia, Serratia, Erwinia, Enterobacteria, Streptomyces, and Pseudomonas, or artificial mutants thereof. [Appendix 6] The method for producing an amino acid mixed solid according to Appendix 1, wherein in the second step, the linear velocity of stirring the amino acid mixed solution is 4 m / s to 17 m / s. [Appendix 7] The method for producing an amino acid mixed solid according to appendix 1, wherein the pressure in the second step is 0.05 to 0.6 atmospheres. [Appendix 8] The method for producing an amino acid mixture solid according to Appendix 1, wherein the third step includes a drying step using a fluidized bed granulator / dryer. [Appendix 9] The method for producing an amino acid mixed solid according to Appendix 1, further comprising the step of concentrating the amino acid mixed solution after carrying out the first step and before carrying out the second step. [Appendix 10] An apparatus for producing an amino acid mixed solid, comprising: a fermenter that produces an amino acid mixed solution by a fermentation process; a thin film dryer that dries and pulverizes the amino acid mixed solution supplied from the fermenter to prepare wet granules; and a granule dryer that dries the wet granules to produce an amino acid mixed solid in granular dosage form, wherein the thin film dryer comprises a thin film dryer stirring unit that stirs the amino acid mixed solution to form a thin film obtained from the amino acid mixed solution on an inner wall of the thin film dryer, and a heating unit that heats the inner wall of the thin film dryer to dry the thin film. [Appendix 11] The apparatus for producing an amino acid mixed solid according to Appendix 10, wherein the stirring section of the thin film drying device and the inner wall of the thin film drying device are spaced apart from each other by a distance of 5 mm to 15 mm. [Appendix 12] An apparatus for producing an amino acid mixed solid according to Appendix 10, wherein the thin film drying device dries the amino acid mixed solution so that the solid concentration in the wet granules is within a range of granule formation concentrations, and the range of the granule formation concentrations is controlled depending on the type of amino acid. [Appendix 13] The apparatus for producing an amino acid mixed solid according to Appendix 10, further comprising a mixing-type granulator that produces granules using at least a portion of the wet granules produced in the thin film drying device as seeds.

Claims

[Claim 1] A first step of preparing an amino acid mixture solution containing amino acids; a second step of stirring the amino acid mixture solution to form a thin film, and drying and pulverizing the formed thin film to prepare wet granules; and a third step of drying the wet granules to produce a granular dosage form of a mixed amino acid solid. In the second step, the amino acid mixture solution is dried so that the solid content concentration in the wet granules is within the range of the granule formation concentration.

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