Lactic acid adsorbent

Abstract

Provided is at least one of a lactic acid adsorbent that easily adsorbs lactic acid even when subjected to regeneration treatment after lactic acid adsorption, a method for recycling a culture medium using the same, and a method for producing a culture medium using the same.　Provided is a lactic acid adsorbent containing a zeolite that: is an MSE-type, an MFI-type, or has a beta skeletal structure; has an alkali metal content of at most 1.6 mass%; and also has a proton-type cation type.

Description

Lactic acid absorbent

[0001] The present disclosure relates to a lactic acid adsorbent containing zeolite, a method for recycling a culture medium using the same, and a method for producing a culture medium using the same.

[0002] Various cell culture methods using culture media are being investigated in fields such as pharmaceutical manufacturing, regenerative medicine, and cultured meat production. When cells are cultured using culture media, lactic acid is produced as a by-product of cell metabolism and accumulates in the culture media. Because lactic acid inhibits cell culture, culture media with accumulated lactic acid are currently discarded.

[0003] However, cell culture media are expensive, and large amounts of media are required for industrial-scale cell culture, making the cost of media an urgent issue in the industrialization of cell culture.

[0004] One solution to this problem is to use dialysis to remove lactic acid from the culture medium in which lactic acid has accumulated, and then reuse (recycle) the culture medium. However, dialysis requires large-scale equipment and is expensive to process. For this reason, for example, Patent Document 1 discloses a method other than dialysis, in which layered double hydroxides are used as a lactic acid adsorbent to remove lactic acid from the culture medium.

[0005] Japanese Patent Application Laid-Open No. 2021-74697

[0006] Lactic acid adsorbents tend to adsorb less lactic acid as the amount of lactic acid adsorbed increases. For this reason, it is expected that lactic acid adsorbents used for lactic acid adsorption will be discarded. However, if lactic acid adsorbents used for lactic acid adsorption are discarded, a large amount of lactic acid adsorbent will be required depending on the amount of culture medium to be reused, which increases the cost of reusing the culture medium. Therefore, there is a need for lactic acid adsorbents that can be repeatedly used for lactic acid adsorption by undergoing a process to remove the lactic acid adsorbed by the lactic acid adsorbent (hereinafter also referred to as a "regeneration process"). A lactic acid adsorbent that can be repeatedly used for lactic acid adsorption is required to easily adsorb lactic acid even after regeneration.

[0007] The present disclosure aims to provide at least one of a lactic acid adsorbent that can easily adsorb lactic acid even when regenerated after lactic acid adsorption, a method for recycling a culture medium using the same, a method for producing a culture medium using the same, and a lactic acid adsorption device using the same.

[0008] The present inventors discovered that, among zeolites having a specific skeletal structure, zeolites having a specific composition are more likely to adsorb lactic acid even after being regenerated after lactic acid adsorption, and thus completed the present invention.

[0009] That is, the present invention is as described in the claims, and the gist of the present disclosure is as follows: [1] A lactic acid adsorbent comprising a zeolite having an MSE type, MFI type, or beta framework structure, an alkali metal content of 1.6 mass% or less, and a proton type cation type. [2] The lactic acid adsorbent according to [1], wherein the molar ratio of alkali metal element to aluminum in the zeolite is 0.40 or less. [3] The SiO of the zeolite ２ / Al ２ O ３The lactic acid adsorbent according to [1] or [2], having a molar ratio of 10 or more and 45 or less. [4] A method for recycling a culture medium, comprising contacting the lactic acid adsorbent according to any one of [1] to [3] with a culture medium in which lactic acid has been produced by culturing cells, tissues, or microorganisms. [5] A method for producing a culture medium using the recycling method according to [4]. [6] A lactic acid adsorption device comprising an adsorption column filled with the lactic acid adsorbent according to any one of [1] to [3], a first supply pipe for supplying a culture medium containing lactic acid to the adsorption column, and a first discharge pipe for discharging the culture medium that has passed through the adsorption column. [7] The lactic acid adsorption device according to [6], further comprising a culture medium supply tank for storing the culture medium containing lactic acid to be supplied to the adsorption column, and the adsorption column is connected to the culture medium supply tank via the first supply pipe. [8] The lactic acid adsorption device according to [6] or [7], wherein the lactic acid supplying device further includes a regenerated medium tank for accommodating the medium discharged from the adsorption column, and the adsorption column is connected to the regenerated medium tank via the first discharge pipe. [9] The lactic acid supplying device further includes a second supply pipe for supplying a regenerated liquid to the adsorption column to remove lactic acid adsorbed by the lactic acid adsorbent, a regenerated liquid tank for accommodating the regenerated liquid to be supplied to the adsorption column, a second discharge pipe for discharging the regenerated liquid that has passed through the adsorption column, and a waste liquid tank for accommodating the regenerated liquid discharged from the adsorption column, and the adsorption column is connected to the regenerated liquid tank via the second supply pipe and to the waste liquid tank via the second discharge pipe.

[10] Use of a zeolite for adsorbing lactic acid, wherein the zeolite has an MSE, MFI, or beta framework structure, an alkali metal content of 1.6 mass% or less, and a proton-type cation type.

[11] The use according to

[10] , wherein the molar ratio of alkali metal element to aluminum in the zeolite is 0.40 or less.

[12] The SiO ２ / Al ２ O ３The use according to

[10] or

[11] , wherein the molar ratio of alkali metal element to aluminum in the zeolite is 10 or more and 45 or less.

[13] Use of a zeolite for producing a lactic acid adsorbent, wherein the zeolite has an MSE type, MFI type, or beta framework structure, an alkali metal content of 1.6 mass% or less, and the cation type is a proton type.

[14] The use according to

[13] , wherein the molar ratio of alkali metal element to aluminum in the zeolite is 0.40 or less.

[15] The SiO ２ / Al ２ O ３ The use according to

[13] or

[14] , wherein the molar ratio is 10 or more and 45 or less.

[0010] According to the present disclosure, it is possible to provide at least one of a lactic acid adsorbent that easily adsorbs lactic acid even when regenerated after lactic acid adsorption, a method for recycling a culture medium using the same, a method for producing a culture medium using the same, and a lactic acid adsorption device using the same.

[0011] FIG. 1 is a diagram showing the configuration of a lactic acid adsorption device 100 using a lactic acid adsorbent. FIG. 2 is a diagram showing the configuration of a lactic acid adsorption device 200 using a lactic acid adsorbent. FIG. 3 is a diagram showing the configuration of a lactic acid adsorption device 300 using a lactic acid adsorbent. FIG. 400 is a diagram showing the configuration of a lactic acid adsorption device 500 using a lactic acid adsorbent.

[0012] First, the meaning of each term in this specification will be explained.

[0013] In this specification, "zeolite" refers to a compound having a regular structure in which skeleton atoms (hereinafter also referred to as "T atoms") are arranged via oxygen (O), and the T atoms are composed of at least either metal atoms or metalloid atoms. Examples of metal atoms include one or more atoms selected from the group consisting of aluminum (Al), titanium (Ti), iron (Fe), zinc (Zn), gallium (Ga), and tin (Sn), with aluminum being preferred. Examples of metalloid atoms include at least one atom selected from the group consisting of boron (B), silicon (Si), germanium (Ge), arsenic (As), antimony (Sb), and tellurium (Te), with silicon being preferred.

[0014] A "zeolite-like substance" is a compound having a regular structure in which T atoms are oxygen-mediated, and the T atoms contain at least one atom other than a metal or a metalloid. Examples of zeolite-like substances include complex phosphorus compounds containing phosphorus (P) as the T atom, such as aluminophosphate (AlPO) and silicoaluminophosphate (SAPO). "Zeolite-like substances" are distinguished from "zeolites," in which the T atoms are composed solely of at least one of metal atoms and metalloid atoms.

[0015] The "regular structure in which T atoms are connected via oxygen (hereinafter also referred to as "skeletal structure")" in zeolites and zeolite-like substances refers to a skeletal structure identified by a skeletal code (hereinafter also referred to simply as a "skeletal code") established by the Structure Commission of the International Zeolite Association, and a skeletal structure having an intergrowth structure described on the International Zeolite Association's website, "http: / / www.iza-structure.org / databases / ." For example, an "MFI-type" skeletal structure is a skeletal structure identified as the skeletal code "MFI." Furthermore, for example, a "beta" skeletal structure is an intergrowth structure composed of multiple single phases intergrowth-wise, and is an intergrowth structure composed of polymorphs Beta_A and Beta_B. In a zeolite having a "beta" framework structure (hereinafter also referred to as "zeolite beta"), the ratio of polymorph Beta_A to polymorph Beta_B (intergrowth ratio) is not particularly limited, but the zeolite beta used as a reference material has an intergrowth structure consisting of approximately 60% polymorph Beta_A and approximately 40% polymorph Beta_B. The zeolite beta used as a reference material is described on the International Zeolite Society website at "https: / / asia.iza-structure.org / IZA-SC / DO_structures / DO_material_rm.php?IFN=Beta." The zeolite framework structure (intergrowth structure) can be identified by comparing it with the XRD pattern of each structure (hereinafter also referred to as "reference pattern") described in the "Zeolite Framework Types" homepage of the International Zeolite Society's Structure Commission at http: / / www.iza-structure.org / databases / . In this embodiment, the terms framework structure (intergrowth structure), crystalline structure, and crystalline phase are used interchangeably.

[0016] An "aluminosilicate" is a composite oxide having a structure consisting of a repeating network of aluminum (Al) and silicon (Si) via oxygen (O). In this embodiment, aluminosilicate also includes a structure consisting of a repeating network of aluminum (Al) and silicon (Si) via oxygen (O), in which a portion of the aluminum (e.g., 30% or less of the aluminum as T atoms) is substituted with other metal atoms. Among aluminosilicates, those having a crystalline XRD peak in their powder X-ray diffraction (hereinafter also referred to as "XRD") pattern are "crystalline aluminosilicates," and those not having a crystalline XRD peak are "amorphous aluminosilicates." Note that zeolites whose T atoms are substantially composed of aluminum (Al) and silicon (Si) fall under the category of "crystalline aluminosilicates." Here, the expression "T atoms substantially consisting of aluminum (Al) and silicon (Si)" does not only mean that the T atoms consist only of aluminum (Al) and silicon (Si), but also means that the T atoms may contain T atoms other than aluminum (Al) and silicon (Si) as long as the effects of the present invention are achieved.

[0017] The XRD pattern was measured using CuKα radiation as the radiation source, and the measurement conditions were as follows: Acceleration current and voltage: 40 mA and 40 kV Radiation source: CuKα radiation (λ=1.5405 Å) Measurement mode: Continuous scan Scan conditions: 40° / min Measurement range: 2θ=3° to 43° Divergence vertical limiting slit: 10 mm Divergence / entrance slit: 1° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0018] The XRD pattern can be measured using a general powder X-ray diffractometer (for example, Ultima IV Protectus, manufactured by Rigaku Corporation). The measured XRD pattern can be analyzed using general analysis software (for example, IGOR Pro 8, manufactured by WaveMetrics). The analysis conditions include the following: A crystalline XRD peak is a peak detected by identifying the 2θ of the peak top in the analysis of the XRD pattern. Fitting conditions: automatic, background refinement, dispersed pseudo-Voigt function (peak shape) Background removal method: fitting method Kα2 removal method: Kα1 / Kα2 ratio = 0.497 Smoothing method: B-Spline curve Smoothing conditions: second-order differential method, σ cut value = 3, χ threshold = 1.5

[0019] The molar ratio of silica to alumina (hereinafter referred to as "SiO ２ / Al ２ O ３ The composition in this embodiment, such as the alkali metal content (also referred to as the "molar ratio") and the alkali metal content, can be determined by X-ray fluorescence analysis (XRF) using a general X-ray fluorescence device (for example, RIX2100, manufactured by Rigaku Corporation). Note that the measurement sample used for XRF is a molded sample obtained by heat-treating the sample in air at 110°C for 30 minutes and then molding 3 g of the sample into a disk sample with a diameter of 50 mm.

[0020] The "zeolite slurry" is a liquid that contains zeolite and a dispersion medium and has fluidity.

[0021] The "solids concentration" of a zeolite slurry refers to the mass proportion of zeolite in the zeolite slurry, and is a concentration calculated by the following formula (1): Solids concentration (mass %) = (mass of zeolite (g) / mass of zeolite slurry (g)) × 100 (1) The mass of the zeolite slurry in the above formula (1) is the mass obtained by measuring the mass of the zeolite slurry, and the mass of zeolite is the mass of the zeolite slurry obtained by removing the dispersant from the zeolite slurry, which is obtained by treating the solids obtained by drying the zeolite slurry after measuring the mass of the zeolite slurry at 600°C in air.

[0022] Next, the lactic acid adsorbent of this embodiment will be described.

[0023] The lactic acid adsorbent of this embodiment contains zeolite (hereinafter also referred to as "the zeolite of this embodiment"). The zeolite of this embodiment has an MSE type, MFI type, or beta framework structure, an alkali metal content of 1.6 mass% or less, and a proton type cation type.

[0024] One of the reasons why the zeolite skeletal structure according to this embodiment is an MSE type, an MFI type, or a beta type is that the MSE type, MFI type, and beta skeletal structures have pores with 10 or more oxygen atoms (hereinafter also referred to as "pores") formed by the T atoms and oxygen atoms that constitute the skeletal structure, and the dimensionality of the pores with 10 or more oxygen rings is 2 or more (two or three dimensions). Pores with 10 or more oxygen rings can adsorb more lactic acid than pores with 9 or less oxygen rings. Furthermore, pores with a dimensionality of 2 or more extend in two or more directions perpendicular to each other, and therefore can diffuse more lactic acid throughout the zeolite than pores with a dimensionality of 1 (pores extending in one direction). Therefore, the zeolite according to the present embodiment, which has an MSE, MFI, or beta skeletal structure, can adsorb more lactic acid than a zeolite having a skeletal structure that does not have pores with 10 or more oxygen rings and a dimensionality of 2 or more.

[0025] Another reason why the zeolite according to the present embodiment has an MSE, MFI, or beta skeletal structure is that the MSE, MFI, or beta skeletal structure has pores with five oxygen atoms (hereinafter also referred to as "5-membered oxygen ring pores") formed in the skeletal structure. Zeolites having 5-membered oxygen ring pores have excellent structural stability and tend to maintain their crystallinity even when subjected to physical and / or chemical treatments (aluminum is less likely to be removed from the skeletal structure). In particular, zeolites having 5-membered oxygen ring pores have excellent acid resistance and tend to maintain their crystallinity even when exposed to acid. For this reason, zeolites according to the present embodiment having an MSE, MFI, or beta skeletal structure tend to maintain their lactic acid adsorption capacity even when subjected to a treatment for removing lactic acid (regeneration treatment) compared to zeolites having a skeletal structure that does not have 5-membered oxygen ring pores.

[0026] In the zeolite according to this embodiment, the alkali metal content is 1.6% by mass or less. In other words, in the zeolite according to this embodiment, the alkali metal content is 0% by mass or more and 1.6% by mass or less. An alkali metal content of 0% by mass means that no alkali metal element is contained. In this specification, not containing a specific component means that the component is not detected (below the lower detection limit). In other words, the zeolite according to this embodiment may or may not contain an alkali metal element, but if it contains an alkali metal element, the alkali metal content is 1.6% by mass or less.

[0027] In the zeolite according to this embodiment, the alkali metal content may be 1.6% by mass or less (0% by mass or more and 1.6% by mass or less), but from the viewpoint of further improving the lactic acid adsorption capacity, it is preferably 1.2% by mass or less (i.e., 0% by mass or more and 1.2% by mass or less), more preferably 0.8% by mass or less (i.e., 0% by mass or more and 0.8% by mass or less), even more preferably 0.7% by mass or less (i.e., 0% by mass or more and 0.7% by mass or less), and particularly preferably 0.4% by mass or less (i.e., 0% by mass or more and 0.4% by mass or less).

[0028] The alkali metal content in this embodiment can be determined by dividing the mass of the alkali metal elements contained in the zeolite according to this embodiment by the mass of the zeolite according to this embodiment and expressing the result as a percentage. When the zeolite according to this embodiment contains two or more alkali metal elements, the alkali metal content refers to the ratio of the total content of these two or more alkali metal elements to the mass of the zeolite according to this embodiment. Here, the mass of the zeolite used to determine the alkali metal content can be the sum of the oxide-equivalent masses of the components contained in the zeolite (total mass), and the mass of the alkali metal elements used to determine the alkali metal content can be the oxide-equivalent mass of the alkali metal elements contained in the zeolite (total mass).

[0029] The alkali metal element that can be contained in the zeolite according to this embodiment can be one or more selected from the group consisting of lithium, sodium, potassium, rubidium, and cesium. From the viewpoint of further improving the lactic acid adsorption capacity, the alkali metal element is preferably at least one of sodium and potassium, and more preferably sodium.

[0030] In the zeolite according to the present embodiment, the state of the alkali metal element is not particularly limited, and may be, for example, a compound (e.g., oxide), a metal (element), an ion, an alloy, or two or more of these. From the viewpoint of further improving the lactate adsorption capacity, the alkali metal element is preferably in the form of an ion.

[0031] In the zeolite according to this embodiment, the alkali metal element is preferably supported on the zeolite, and more preferably supported as a counter ion (hereinafter simply referred to as a "counter ion") for compensating for the charge of the zeolite framework. In this embodiment, "containing a specific element" means that the specific element is contained in the zeolite, and the specific element may be contained in any state and at any site. On the other hand, "supporting a specific element" means that the specific element is contained in the zeolite as a component other than T atoms. Examples of the supported form of the specific element include a form in which the specific element is supported on at least one of the outer surface of the zeolite (the surface of the zeolite excluding the inner surfaces of the pores) and the inner surfaces of the pores.

[0032] The cation type of the zeolite according to this embodiment is the proton type. In this embodiment, as an example, when 2 g of zeolite is dispersed in 18 g of pure water at 25° C. (i.e., the solid content concentration is 10 mass %), the pH of the zeolite slurry (hereinafter also referred to as “slurry pH”) is less than 7, and the cation type of the zeolite can be considered to be the proton type.

[0033] Here, the cation type is a proton type when the counter ion is a proton (H ＋ ), but it does not necessarily mean that all of the counter ions are protons, and it is acceptable for a trace amount of alkali metal ions to be contained as counter ions in addition to protons. In this embodiment, the trace amount of alkali metal ions refers to an amount of alkali metal ions such that the alkali metal content is 1.6 mass % or less. In other words, zeolites whose cation type is proton type include zeolites whose counter ions are all protons and zeolites whose counter ions are protons (H ＋ ) and a zeolite containing alkali metal ions in an amount such that the alkali metal content is 1.6 mass % or less. Note that zeolites whose cation type is proton type contain protons (H ＋ ) and alkali metal ions.＋ ) and counter ions other than alkali metal ions are not included. ＋ ) and alkali metal ions, but it also means that inevitable impurities may be contained as counter ions to the extent that they do not affect the effects of the present invention. In this embodiment, proton is synonymous with hydrogen ion, and proton ions ( １ H ＋ ) is not limited to a particular isotope.

[0034] SiO of the zeolite according to this embodiment ２ / Al ２ O ３ From the viewpoint of further improving the lactic acid adsorption capacity, the molar ratio is preferably 10 or more, more preferably 15 or more, and even more preferably 18 or more. ２ / Al ２ O ３ From the viewpoint of further improving the lactate adsorption capacity, the molar ratio is preferably 45 or less, more preferably 40 or less, and even more preferably 35 or less. ２ / Al ２ O ３ The upper and lower limit values ​​of the molar ratio may be any combination of the upper and lower limit values ​​described above, but from the viewpoint of further improving the lactate adsorption capacity, it is preferably 10 or more and 45 or less, more preferably 15 or more and 40 or less, and even more preferably 18 or more and 35 or less.

[0035] In the zeolite according to this embodiment, the molar ratio of alkali metal elements to aluminum (hereinafter also referred to as the "M / Al molar ratio") is not particularly limited as long as the alkali metal content is 1.6% by mass or less. However, from the viewpoint of further improving the lactic acid adsorption capacity, it is preferably 0.40 or less (i.e., 0 to 0.40), more preferably 0.35 or less (i.e., 0 to 0.35), even more preferably 0.30 or less (i.e., 0 to 0.30), and particularly preferably 0.10 or less (i.e., 0 to 0.10). When the zeolite according to this embodiment contains two or more alkali metal elements, the M / Al molar ratio refers to the ratio of the total molar amount of these two or more alkali metal elements to the number of moles of aluminum. Furthermore, an M / Al molar ratio of 0 means that no alkali metal elements are contained.

[0036] The T atoms (T atoms constituting the framework structure) of the zeolite according to this embodiment may be at least either metal atoms or metalloid atoms, and are not particularly limited, but from the viewpoint of further improving the lactate adsorption capacity, they are preferably substantially composed of aluminum (Al) and silicon (Si). In other words, the zeolite according to this embodiment is preferably a crystalline aluminosilicate.

[0037] The zeolite according to this embodiment can be produced by adjusting at least one of the alkali metal content and the cation type of the zeolite used as a raw material (hereinafter also referred to as "raw material zeolite"). Zeolite having an MSE, MFI, or beta skeletal structure is used as the raw material zeolite. Note that when a zeolite having an alkali metal content of 1.6 mass% or less and a proton cation type is used as the raw material zeolite (zeolite having an MSE, MFI, or beta skeletal structure), adjustment of the alkali metal content and the cation type is not necessary.

[0038] First, a method for adjusting the alkali metal content of the raw material zeolite will be described. To adjust the alkali metal content of the raw material zeolite, at least one of an acid treatment and an ammonium treatment can be used.

[0039] The acid treatment for adjusting the alkali metal content is a treatment in which the raw material zeolite is brought into contact with an acid. By subjecting the raw material zeolite to the acid treatment, the alkali metal content of the raw material zeolite can be reduced compared to that before the acid treatment.

[0040] The method for contacting the raw zeolite with the acid is not particularly limited, but may include, for example, a method in which the raw zeolite and the acid are mixed together.

[0041] In the acid treatment, hydrochloric acid can be used as the acid to be brought into contact with the raw zeolite. The concentration of hydrochloric acid is optional, but can be, for example, 0.5 mol / L or more and 4 mol / L or less. In the acid treatment, the raw zeolite may be brought into contact with the acid in the presence of a solvent. Examples of the solvent include at least one of water and an alcohol, and water is preferred.

[0042] The conditions for the acid treatment are not particularly limited as long as the alkali metal content of the raw zeolite is 1.6% by mass or less. However, the alkali metal content of the raw zeolite decreases as the mass ratio of acid to raw zeolite (hereinafter also referred to as the "acid / zeolite mass ratio") increases, the alkali metal content of the raw zeolite decreases as the contact time between the raw zeolite and the acid (hereinafter also referred to as the "acid contact time") increases, and the alkali metal content of the raw zeolite decreases as the contact temperature between the raw zeolite and the acid (hereinafter also referred to as the "acid contact temperature") increases. Therefore, it is preferable to appropriately adjust the acid / zeolite mass ratio, acid contact time, and acid contact temperature in consideration of the above-mentioned characteristics so that the alkali metal content of the raw zeolite is 1.6% by mass or less. The acid / zeolite mass ratio can be, for example, 0.1 to 5.0 or 0.5 to 3.0. The acid contact time can be, for example, 0.1 to 10 hours or 0.3 to 2 hours. The acid contact temperature is, for example, 20°C or higher and 100°C or lower, or 40°C or higher and 70°C or lower.

[0043] The acid-treated raw zeolite may be further subjected to at least one of a washing treatment and a drying treatment. The washing treatment is a treatment for washing the zeolite. For example, the washing treatment may be performed by washing the raw zeolite with pure water. The drying treatment is a treatment for removing moisture adsorbed on the raw zeolite. The drying conditions are arbitrary as long as moisture can be removed from the raw zeolite. One example of the drying conditions is drying the raw zeolite in an air atmosphere at a temperature of 50°C to 200°C for 1 hour to 24 hours.

[0044] The ammonium treatment for adjusting the alkali metal content is a treatment in which a raw material zeolite is brought into contact with a solution containing ammonium cations (hereinafter also referred to as an "ammonium solution"). By subjecting the raw material zeolite to the ammonium treatment, the alkali metal content of the raw material zeolite can be reduced compared to that before the ammonium treatment.

[0045] The method for contacting the raw zeolite with the ammonium solution is not particularly limited, but for example, a method in which the raw zeolite is mixed with the ammonium solution can be mentioned.

[0046] In the ammonium treatment, the ammonium solution that comes into contact with the raw zeolite contains at least ammonium cations and a solvent. The ammonium cations contained in the ammonium solution can be generated, for example, by mixing an ammonium cation source with a solvent. The ammonium cation source may be any source that generates ammonium cations when mixed with a solvent, and is not particularly limited, but examples include at least one of ammonia and an ammonium salt. Examples of ammonium salts include one or more selected from the group consisting of ammonium nitrate, ammonium chloride, ammonium acetate, ammonium carbonate, ammonium bicarbonate, ammonium bromide, ammonium iodide, ammonium vanadate, ammonium carbamate, ammonium succinate, and diammonium adipate. The solvent contained in the ammonium solution can be, for example, at least one of water and alcohol, with water being preferred.

[0047] The conditions for the ammonium treatment are not particularly limited as long as the alkali metal content is 1.6% by mass or less. However, the alkali metal content of the raw zeolite decreases as the mass ratio of the ammonium cation source to the raw zeolite (hereinafter also referred to as the "ammonium cation source / zeolite mass ratio") increases, and the alkali metal content of the raw zeolite decreases as the contact time between the raw zeolite and the ammonium solution (hereinafter also referred to as the "ammonium contact time") increases. Therefore, it is preferable to appropriately adjust the ammonium cation source / zeolite mass ratio and the ammonium contact time, taking these characteristics into consideration, so that the alkali metal content of the raw zeolite is 1.6% by mass or less. The ammonium cation source / zeolite mass ratio can be, for example, from 1 to 10, or from 2 to 5. The ammonium contact time can be, for example, from 0.1 to 24 hours, or from 0.2 to 4 hours.

[0048] The ammonium-treated raw zeolite may be further subjected to at least one of a washing treatment and a drying treatment. The washing treatment and drying treatment that can be performed on the ammonium-treated raw zeolite are the same as the washing treatment and drying treatment that can be performed on the acid-treated raw zeolite, respectively, and therefore detailed explanations will be omitted. Furthermore, the ammonium treatment (and at least one of the optional washing treatment and drying treatment) may be performed multiple times so that the alkali metal content of the raw zeolite becomes 1.6 mass% or less.

[0049] Next, a method for adjusting the cation type of the raw material zeolite will be described. To adjust the cation type of the raw material zeolite, at least one of a calcination treatment and a steam treatment can be used.

[0050] The calcination treatment for adjusting the cation type is a treatment in which the raw zeolite is calcined. The calcination treatment is a treatment in which the raw zeolite is calcined in a dry gas having a moisture content of less than 2% by volume, and is distinguished from the steam treatment described below. The dry gas may be one or more gases having a moisture content of less than 2% by volume selected from the group consisting of air, nitrogen, oxygen, helium, and argon, and is preferably air having a moisture content of less than 2% by volume.

[0051] By subjecting a raw material zeolite whose cation type is ammonium to a calcination treatment, the cation type of the raw material zeolite can be changed to proton type. Note that even if a raw material zeolite whose cation type is other than ammonium type is subjected to a calcination treatment, the cation type is not adjusted (changed). Here, the cation type being ammonium type means that the counter ion is an ammonium ion (NH ４ ＋ ), but all of the counter ions contained in the zeolite are ammonium ions (NH ４ ＋ ), but also means that it is an ammonium ion (NH ４ ＋ ) and a trace amount of alkali metal ions may be contained as counter ions.

[0052] The conditions for the calcination treatment are not particularly limited as long as the cation type of the raw zeolite becomes the proton type. However, the longer the calcination time of the raw zeolite (hereinafter also simply referred to as the "calcination time"), the more likely the cation type of the raw zeolite becomes the proton type, and the higher the calcination temperature of the raw zeolite (hereinafter also simply referred to as the "calcination temperature"), the more likely the cation type of the raw zeolite becomes the proton type. Therefore, it is preferable to appropriately adjust the calcination time and calcination temperature in consideration of the above-mentioned characteristics so that the cation type of the raw zeolite becomes the proton type. The calcination time can be, for example, from 0.5 hours to 5 hours, or from 1 hour to 3 hours. The calcination temperature can be, for example, from 400°C to 900°C, or from 500°C to 800°C.

[0053] In the calcination treatment for adjusting the cation type, if the cation type of the raw zeolite to be calcined is not ammonium, the raw zeolite can be subjected to ammonium treatment prior to the calcination treatment. By performing the ammonium treatment on the raw zeolite, the counter ions of the raw zeolite are ion-exchanged with ammonium cations, thereby changing the cation type to ammonium. The ammonium treatment for changing the cation type to ammonium is the same treatment as the ammonium treatment for adjusting the alkali metal content. In other words, by performing the ammonium treatment on the raw zeolite, not only can the alkali metal content of the raw zeolite be adjusted, but the cation type can also be changed to ammonium. Since the ammonium treatment for changing the cation type to ammonium is the same treatment as the ammonium treatment for adjusting the alkali metal content, a detailed description thereof will be omitted.

[0054] The conditions for the ammonium treatment to convert the cation type to the ammonium type are not particularly limited as long as the cation type of the raw material zeolite is ammonium type, but the higher the ammonium content, the more likely the cation type is to be ammonium type, and the longer the ammonium contact time, the more likely the cation type is to be ammonium type. Therefore, it is preferable to appropriately adjust the ammonium content and ammonia contact time in consideration of these characteristics so that the cation type of the raw material zeolite is ammonium type.

[0055] Steam treatment for adjusting the cation type involves heating raw zeolite in one or more gases (hereinafter also referred to as "steam") containing water vapor (vaporized water) and selected from the group consisting of air, nitrogen, oxygen, helium, and argon. The steam used in the steam treatment is a gas with a water vapor content (hereinafter also referred to as "moisture content") of 2% by volume or more. The moisture content (volume % of steam) is a calculated value assuming that the gas contained in the steam is an ideal gas, and can be determined from equation (2). If steam treatment is performed on raw zeolite whose cation type is ammonium, the cation type of the raw zeolite can be changed to proton type. Note that even if steam treatment is performed on raw zeolite whose cation type is other than ammonium type, the cation type is not adjusted (changed). Moisture content [volume %] = n ｖ / n ｓ × 100 (2) In the above formula (2), n ｖ represents the number of moles of water vapor contained in the steam [mol], and n ｓ represents the total number of moles [mol] of all components contained in the steam.

[0056] In this embodiment, the steam used in the steam treatment is preferably air having a moisture content of 2% by volume or more.

[0057] The method of steam treatment is not particularly limited, but may be, for example, by placing the raw zeolite in steam and heating it, or by blowing heated steam onto the raw zeolite.

[0058] The conditions for the steam treatment are not particularly limited as long as they result in the proton type cation. However, the higher the moisture content of the steam, the more likely the raw zeolite is to be converted to the proton type; the longer the heating time of the raw zeolite in steam (hereinafter also referred to as the "steam heating time"), the more likely the raw zeolite is to be converted to the proton type; and the higher the heating temperature of the raw zeolite in steam (hereinafter also referred to as the "steam heating temperature"), the more likely the raw zeolite is to be converted to the proton type. Therefore, it is preferable to appropriately adjust the moisture content of the steam, the steam heating time, and the steam heating temperature, taking into account the above-mentioned characteristics, so that the raw zeolite is converted to the proton type cation. The moisture content of the steam is, for example, 3% by volume to 50% by volume, or 5% by volume to 30% by volume. The steam heating time is, for example, 30 minutes to 5 hours, or 1 hour to 3 hours. The steam heating temperature is, for example, 400°C to 800°C, or 500°C to 700°C.

[0059] Here, in the steam treatment for adjusting the cation type, if the cation type of the raw material zeolite is not ammonium, the raw material zeolite can be subjected to ammonium treatment prior to the steam treatment. By performing the ammonium treatment, the counter ions of the raw material zeolite are ion-exchanged with ammonium cations, thereby changing the cation type to ammonium. The ammonium treatment for changing the cation type to ammonium has been described above, so a detailed description thereof will be omitted.

[0060] Next, a method for producing the raw material zeolite will be described. The raw material zeolite can be produced by a conventionally known method and is not particularly limited. For example, the raw material zeolite can be produced by a method including a crystallization step of crystallizing a composition containing an alumina source, a silica source, an alkali source, and water (hereinafter also referred to as "raw material composition"). Note that commercially available zeolites having an MSE, MFI, or beta framework structure may be used as the raw material zeolite.

[0061] The alumina source contained in the raw material composition is a compound containing aluminum (Al), and examples thereof include one or more selected from the group consisting of aluminum isopropoxide, aluminum sulfate, aluminum chloride, aluminum hydroxide, pseudoboehmite, alumina sol, and amorphous aluminosilicate. Note that substances containing aluminum (Al) and silicon (Si), such as amorphous aluminosilicate, can be used not only as an alumina source but also as a silica source, which will be described later.

[0062] The silica source contained in the raw material composition is a compound containing silicon (Si), and examples thereof include one or more selected from the group consisting of silica sol, fumed silica, colloidal silica, precipitated silica, sodium silicate, amorphous silicic acid, and amorphous aluminosilicate.

[0063] The alkali source contained in the raw material composition is a compound containing an alkali metal element, and examples thereof include compounds containing one or more alkali metal elements selected from the group consisting of sodium, potassium, cesium, and rubidium, with a compound containing at least one of sodium and potassium being preferred. The alkali source may be, for example, one or more salts selected from the group consisting of hydroxides, carbonates, chlorides, bromides, iodides, and sulfates containing alkali metal elements. Preferred alkali sources include at least one selected from the group consisting of potassium hydroxide, sodium hydroxide, sodium carbonate, sodium chloride, sodium bromide, sodium iodide, and sodium sulfate. The alkali source is not limited to the form of a salt, and may be in a form other than a salt, such as sodium silicate.

[0064] The water contained in the raw material composition may be, for example, distilled water, deionized water, pure water, or two or more of these. Note that when the raw materials other than water contained in the raw material composition contain water, such as hydrates, structural water, or solvents, the water contained in the raw materials other than water can be considered to be the water contained in the raw material composition.

[0065] The raw material composition may be composed only of an alumina source, a silica source, an alkali source, and water, or may contain other raw materials in addition to these. Examples of other raw materials include a structure-directing agent source.

[0066] The structure-directing agent source may be any substance capable of generating (releasing) a structure-directing agent (hereinafter also referred to as "SDA") that directs an MSE-type, MFI-type, or beta skeletal structure in the raw material composition, and any conventionally known substance may be used. For example, a compound containing an SDA may be used as the structure-directing agent source, and further, a salt containing an SDA may be used. Examples of salts containing an SDA include one or more salts selected from chlorides, bromides, iodides, and hydroxides containing an SDA.

[0067] Examples of SDAs directing an MSE-type skeletal structure include at least one selected from the group consisting of a 1,1'-(1,4-cyclohexanediyl)dipiperidinium cation, a 1,1'-(1,4-cyclohexanediyl)dipyrrolidinium cation, an N,N,N',N'-tetraethylbicyclo[2.2.2]oct-7-ene-2,3:5,6-dipyrrolidinium cation, and a dimethyldipropylammonium cation. Examples of SDAs directing an MFI-type skeletal structure include at least one selected from the group consisting of a tetrapropylammonium cation, a tetrabutylammonium cation, and cyclohexanol. Examples of substances directing a beta-type skeletal structure include at least one selected from the group consisting of a tetraethylammonium cation, a 4,4'-trimethylenebis(1-benzyl-1-methylpiperidinium) cation, and a benzyltrimethylammonium cation.

[0068] The composition of the raw material composition can be appropriately selected depending on the skeletal structure of the zeolite to be produced, and the like. As an example of a preferred composition, the following molar composition can be mentioned. Note that the ratios in the following compositions are molar (mol) ratios, and SiO ２ is silica (mol), Al ２ O ３is alumina (mol), H ２ O is water (mol), M is alkali metal element (mol), SDA is organic structure directing agent (mol), and OH is the total amount (mol) of hydroxide ions in the raw material composition. ２ A molar ratio of 0 means that no SDA is contained. ２ / Al ２ O ３ Molar ratio = 15 or more, preferably 18 or more, and 50 or less, preferably 40 or less, SDA / SiO ２ Molar ratio M / SiO = 0 or more, preferably 0.03 or more, and 1.0 or less, preferably 0.5 or less ２ Molar ratio = 0.03 or more, preferably 0.10 or more, and 0.60 or less, preferably 0.40 or less ２ O / SiO ２ Molar ratio OH / SiO = 5 or more, preferably 10 or more, and 50 or less, preferably 30 or less ２ Molar ratio = 0.05 or more, preferably 0.08 or more, and 0.60 or less, preferably 0.40 or less

[0069] In the crystallization step, the raw material composition described above is crystallized. The crystallization of the raw material composition may be carried out in the presence of seed crystals. An example of a method for crystallizing the raw material composition in the presence of seed crystals is a method of mixing the raw material composition with seed crystals and crystallizing the resulting mixture. The seed crystals may be appropriately selected depending on the skeletal structure of the zeolite to be produced. For example, when a raw material zeolite having an MSE skeletal structure is to be produced, it is preferable to use a zeolite having an MSE skeletal structure as the seed crystals. When a raw material zeolite having an MFI skeletal structure is to be produced, it is preferable to use a zeolite having an MFI skeletal structure as the seed crystals. When a raw material zeolite having a beta skeletal structure is to be produced, it is preferable to use a zeolite having a beta skeletal structure as the seed crystals.

[0070] The amount of seed crystals used for crystallization may be appropriately determined depending on the framework structure of the zeolite to be produced, and is not particularly limited. However, the amount of aluminum and silicon in the raw material composition (excluding seed crystals) may be adjusted to Al ２ O ３ and SiO ２ The aluminum and silicon in the seed crystals relative to the converted total mass are respectively Al ２ O ３ and SiO ２ The proportion of the converted total mass (hereinafter also referred to as "seed crystal content") can be, for example, 1% by mass or more and 10% by mass or less, or 2% by mass or more and 5% by mass or less.

[0071] The crystallization treatment of the raw material composition is not particularly limited as long as it can crystallize the raw material composition so as to obtain a zeolite having an MSE, MFI, or beta skeletal structure. A preferred crystallization treatment method is a method in which the raw material composition is subjected to hydrothermal treatment. The hydrothermal treatment conditions may be appropriately set depending on the skeletal structure of the raw material zeolite to be produced, and examples thereof include the following conditions: Treatment temperature: 110°C or higher, 130°C or higher, or 150°C or higher, and 210°C or lower, 200°C or lower, or 190°C or lower Treatment time: 8 hours or higher, 10 hours or higher, or 15 hours or higher, and 500 hours or lower, or 300 hours or lower Treatment pressure: autogenous pressure

[0072] The method for producing the raw zeolite may include, in addition to the crystallization step described above, one or more steps selected from the group consisting of a washing step, a drying step, and an SDA removal step.

[0073] The washing step is a step of washing the raw zeolite obtained by crystallization. For example, in the washing step, the raw zeolite obtained by crystallization may be washed with pure water.

[0074] The drying step is a step of removing moisture from the crystallized raw zeolite or the washed raw zeolite. The conditions for the drying step are not particularly limited as long as moisture can be removed from the raw zeolite. For example, the drying temperature may be 100°C or higher and 150°C or lower. For example, the drying time may be 2 hours or higher and 20 hours or lower. For example, the drying atmosphere may be air.

[0075] The SDA removal step is a step of removing SDA contained in a raw zeolite obtained by crystallization, a washed raw zeolite, or a dried raw zeolite. Usually, a zeolite crystallized using an SDA has an SDA supported in its pores. By including the SDA removal step, the SDA supported on the raw zeolite can be removed.

[0076] The SDA removal treatment is not particularly limited as long as it removes the SDA, and for example, a calcination treatment (a treatment in which the raw zeolite is calcined in a dry gas with a moisture content of less than 2% by volume) can be used. The conditions for the calcination treatment to remove the SDA are not particularly limited as long as the SDA is removed. For example, the calcination temperature can be 400°C or higher and 800°C or lower. Also, for example, the calcination time can be 1 hour or higher and 5 hours or lower. Also, for example, the atmosphere during the calcination can be an ambient atmosphere consisting of dry air.

[0077] By the above-described production method, a raw material zeolite (a zeolite having an MSE, MFI, or beta framework structure) can be produced.

[0078] The lactic acid adsorbent of this embodiment may be composed solely of the zeolite of this embodiment, or may contain other components in addition to the zeolite of this embodiment. Furthermore, the lactic acid adsorbent of this embodiment may be in the form of a powder or a molded body. The molded lactic acid adsorbent may be composed solely of the zeolite of this embodiment, but preferably further contains, in addition to the zeolite of this embodiment, one or more selected from the group consisting of a binder, a molding aid, and water.

[0079] The binder may be an organic binder, an inorganic binder, or both. Examples of organic binders include at least one binder selected from the group consisting of polyethylene oxide, hydroxyethyl methylcellulose, starch, corn starch, molasses, lactose, gelatin, dextrin, gum arabic, alginic acid, acrylic acid, polyethylene glycol, and polyvinylpyrrolidone. Examples of inorganic binders include at least one binder selected from the group consisting of clay, silica, alumina, and zirconia. From the viewpoint of further improving lactic acid adsorption capacity, the binder is preferably at least one binder selected from the group consisting of starch, acrylic acid, clay, silica, alumina, and zirconia, and more preferably silica and clay.

[0080] The content of the binder in the lactic acid adsorbent of this embodiment can be, for example, 5% by mass or more and 70% by mass or less relative to 100% by mass of the lactic acid adsorbent.

[0081] Examples of molding aids include water-soluble or water-insoluble celluloses such as one or more selected from the group consisting of carboxylmethylcellulose (hereinafter also referred to as "CMC"), hydroxycellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, and cellulose nanofibers; guar gum derivatives such as at least one of guar gum and hydroxypropylguar gum; polysaccharides such as one or more selected from the group consisting of xanthan gum, welan gum, and gellan gum, which belong to biogums; polyethyleneimine derivatives; polyvinylpyrrolidone (hereinafter also referred to as "PVP"); alcohols such as one or more selected from the group consisting of glycerin, polyvinyl alcohol, and ethylene glycol derivatives; cationic, anionic, or nonionic surfactants; aqueous urethane; polyacrylic acid derivatives, etc. These may be used alone or in combination of two or more. The CMC may be sodium carboxymethylcellulose. Preferred molding aids include at least one of CMC and hydroxypropyl cellulose.

[0082] The content of the molding aid in the lactic acid adsorbent of this embodiment can be, for example, 0.1% by mass or more and 10% by mass or less relative to 100% by mass of the lactic acid adsorbent.

[0083] The water content in the lactic acid adsorbent of this embodiment can be, for example, 0.1% by mass or more and 40% by mass or less relative to 100% by mass of the lactic acid adsorbent.

[0084] The inclusion of a binder in addition to the zeolite according to the present embodiment in the lactic acid adsorbent of the present embodiment makes it easier to mold the lactic acid adsorbent of the present embodiment into a predetermined shape. Furthermore, the inclusion of a molding aid and water in addition to the zeolite and binder according to the present embodiment in the lactic acid adsorbent of the present embodiment further improves moldability. A lactic acid adsorbent in the form of a molded body can be produced, for example, by molding a mixture of the zeolite according to the present embodiment and a binder (and, if necessary, a molding aid and water) into a predetermined shape and firing it. The shape of the molded body is not particularly limited, but may be at least one selected from the group consisting of spherical, approximately spherical, ellipsoidal, cylindrical, polyhedral, and amorphous.

[0085] The lactic acid adsorbent of this embodiment can be used as an adsorbent for adsorbing lactic acid, for example, as an adsorbent for adsorbing lactic acid contained in a culture medium.

[0086] The adsorption of lactic acid from a culture medium by the lactic acid adsorbent of this embodiment can be carried out by contacting the lactic acid adsorbent of this embodiment with a culture medium containing lactic acid. The method for contacting the lactic acid adsorbent of this embodiment with a culture medium is not particularly limited as long as it is carried out in a manner that brings the zeolite of this embodiment into contact with the culture medium, and examples of the method include a method of mixing (stirring) the lactic acid adsorbent of this embodiment with the culture medium, a method of filling a column with the lactic acid adsorbent of this embodiment and passing the culture medium through the column, and a method of pouring the culture medium into a container having the lactic acid adsorbent of this embodiment immobilized on the wall or bottom thereof.

[0087] The medium to be contacted with the lactic acid adsorbent of this embodiment may be a medium containing lactic acid. However, from the perspective of the Sustainable Development Goals (SDGs), it is preferable that the medium contain lactic acid produced by culturing cells, tissues, or microorganisms. The cells and tissues cultured in the medium may be of animal or plant origin. Furthermore, examples of the microorganisms cultured in the medium include one or more species selected from the group consisting of bacteria, viruses, and fungi. The medium in which the cells, tissues, or microorganisms are cultured may contain, in addition to lactic acid, one or more waste products or metabolites, such as ammonia.

[0088] Examples of lactic acid to be removed by the lactic acid adsorbent of this embodiment include L-lactic acid, D-lactic acid, and a mixture of L-lactic acid and D-lactic acid. At least one of a mixture of L-lactic acid and D-lactic acid and L-lactic acid is preferred, and L-lactic acid is more preferred. The lactic acid is neutral (CH ３ CH(OH)COOH), anion (CH ３ CH(OH)COO － ) and cation (CH ３ CH(OH)COOH ２ ＋ or CH ３ CH(OH ２ ＋ ) COOH), and neutral or anionic lactic acid is preferable. The lactic acid adsorbed by the lactic acid adsorbent of this embodiment may be at least one of neutral, anionic, and cationic. The lactate anion may exist in the culture medium as a lactate salt. Examples of the lactate salt include one or more selected from the group consisting of sodium lactate, potassium lactate, and calcium lactate. Furthermore, the lactic acid to be adsorbed and removed is preferably dissolved in the culture medium.

[0089] The lactic acid-containing medium provides a growth environment for the culture subject and is composed of components necessary for the growth of the culture subject. The composition of the medium can be any conventionally known composition suitable for the culture subject, but it preferably contains at least a carbon source, inorganic salts, and water, and more preferably further contains one or more selected from the group consisting of amino acids, vitamins, albumin, and growth factors.

[0090] The carbon source may include carbohydrates such as one or more selected from the group consisting of glucose (D-glucose), maltose, molasses, dextrin, glycerin, and starch.

[0091] Examples of inorganic salts include calcium chloride (CaCl ２ ), copper(II) sulfate (CuSO ４ ), potassium chloride (KCl), magnesium chloride (MgCl ２ ), magnesium sulfate (MgSO ４), sodium chloride (NaCl), sodium bicarbonate (NaHCO ３ ), sodium dihydrogen phosphate (NaH ２ P.O. ４ ), zinc sulfate (ZnSO ４ ), iron(II) sulfate (FeSO ４ ), iron(II) nitrate (Fe(NO ３ ) ２ ) and iron(III) nitrate (Fe(NO ３ ) ３ ) and the like.

[0092] Examples of the amino acid include one or more amino acids selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Amino acids other than glycine may be used in either the L- or D-form, or a mixture thereof (e.g., DL-form), but the L-form is preferably used.

[0093] Examples of vitamins include one or more selected from the group consisting of L-ascorbic acid, biotin, D-calcium pantothenate, choline chloride, folic acid, inositol, niacinamide, p-aminobenzoic acid, pyridoxine, riboflavin, thiamine, cyanocobalamin, hydroxocobalamin, and i-inositol.

[0094] Examples of albumin include one or more selected from the group consisting of bovine serum albumin (BSA), human serum albumin, chicken ovalbumin, mouse serum albumin, rat serum albumin, porcine serum albumin, and sheep serum albumin.

[0095] Examples of the growth factor include one or more selected from the group consisting of fibroblast growth factor basic, epidermal growth factor (EGF), brain-derived neurotrophic factor (BDNF), human interleukin 2 (IL2), vascular endothelial growth factor (VEGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF).

[0096] The medium may consist solely of the above-mentioned components, or may contain other components, such as one or more selected from the group consisting of pigments (colorants) such as phenol red, iron-binding glycoproteins such as transferrin, growth supplements such as fetal bovine serum (FBS), antioxidants such as sodium pyruvate and glutathione, and buffers such as HEPES.

[0097] The culture medium to be brought into contact with the lactic acid adsorbent of this embodiment may be in any form of liquid, solid, gel, or sol, but is preferably liquid, as this allows for easier contact between the zeolite of this embodiment and the culture medium.

[0098] In the culture medium to be contacted with the lactic acid adsorbent of this embodiment, the concentration of lactic acid can be appropriately set depending on the amount of zeolite to be in contact with the culture medium, and can be, for example, 0.01% by mass or more and 1% by mass or less relative to 100% by mass of the culture medium containing lactic acid.

[0099] Specific media to be brought into contact with the lactic acid adsorbent of this embodiment include an animal cell culture medium in which lactic acid is produced by culturing (e.g., a human-derived cell culture medium), an aquatic plant cell culture medium in which lactic acid is produced by culturing, or a microbial culture medium in which lactic acid is produced by culturing. Examples of the human-derived cell culture medium include a commercially available medium for pluripotent stem cells (e.g., StemFit™ (Ajinomoto Co., Inc.) ＴＭ ), and human mesenchymal stem cells (hMSCs) were cultured in a commercially available serum-free medium for hMSCs (e.g., CiMS ＴＭ), a culture medium in which human mesenchymal stem cells or human embryonic kidney cells (HEK293 cells) are cultured in a serum-containing medium for animal cells (for example, a medium in which fetal bovine serum is added to the basal medium D-MEM), or a culture medium in which human-derived cells such as neural progenitor cells, vascular endothelial cells, mesenchymal progenitor cells, cardiac muscle cells, skeletal myoblasts, skeletal muscle cells, smooth muscle cells, corneal epithelial cells, corneal endothelial cells, retinal pigment epithelial cells, chondrocytes, or fibroblasts are cultured in an appropriate medium. Furthermore, examples of cell culture media in which non-human-derived cells are cultured include, for example, a culture medium in which Chinese hamster ovary cells (CHO cells) are cultured in a commercially available medium for antibody-producing cell lines (for example, EX-CELL Advanced CHO Fed-Batch Medium manufactured by SAFC Biosciences). ＴＭ African green monkey kidney epithelial cells (Vero cells) were cultured in a commercially available serum-free medium for Vero cells (NutriVero Flex 10, manufactured by Biological Industries, Inc.). ＴＭ ), or insect cells (e.g., Sf9 cells) cultured in an insect cell medium (e.g., IS Sf Insect Culture, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. ＴＭ Examples of the culture medium include a culture medium cultured using

[0100] The pH of the culture medium to be brought into contact with the lactic acid adsorbent of this embodiment varies depending on the culture target, but may be, for example, 3 or more and 10 or less, or 6 or more and 8 or less.

[0101] The contact of the lactic acid adsorbent of this embodiment with the culture medium may be carried out simultaneously (in parallel) with the culture step of culturing cells, tissues, or microorganisms, or may be carried out as a separate step before or after the culture step.

[0102] The contact temperature between the lactic acid adsorbent and the culture medium in this embodiment is not particularly limited, but is preferably 0°C or higher and 80°C or lower from the viewpoint of excellent lactic acid removal efficiency, more preferably 10°C or higher and 60°C or lower from the viewpoint of preventing irreversible deterioration of proteins contained in the culture medium, and even more preferably 25°C or higher and 40°C or lower when the culture medium contains cells or microorganisms.

[0103] The contact time between the lactic acid adsorbent and the culture medium in this embodiment is not particularly limited, but can be, for example, 0.1 hours or more and 30 hours or less.

[0104] The lactic acid adsorbent of this embodiment can adsorb lactic acid from a culture medium containing lactic acid by contacting the lactic acid adsorbent of this embodiment with the culture medium containing lactic acid produced by culturing cells, tissues, or microorganisms (hereinafter also referred to as a "lactic acid-producing medium"), thereby removing at least a portion of the lactic acid contained in the medium and reducing the amount of lactic acid that interferes with the culture. The medium with a reduced amount of lactic acid can be reused as a medium for culturing cells, tissues, or microorganisms. In other words, the present invention also provides a method for recycling a culture medium, which includes contacting the lactic acid adsorbent of this embodiment with the lactic acid-producing medium. Furthermore, this recycling method can also be used to produce a medium (recycled medium) with a reduced amount of lactic acid compared to the lactic acid-producing medium before contacting it with the lactic acid adsorbent of this embodiment.

[0105] The lactic acid adsorbent of this embodiment to which lactic acid has been adsorbed (hereinafter simply referred to as "lactic acid adsorbent with lactic acid adsorbed") can be reused for adsorbing lactic acid by subjecting it to a regeneration treatment for removing lactic acid. Note that the lactic acid adsorption treatment and the regeneration treatment may be repeated multiple times.

[0106] The regeneration treatment may be any treatment capable of removing lactic acid (at least a portion of the lactic acid) adsorbed to the lactic acid adsorbent. However, from the viewpoint of further improving the lactic acid adsorption capacity after the regeneration treatment, an acid treatment (hereinafter also referred to as "acid regeneration treatment") is preferred, in which the lactic acid adsorbent to which lactic acid has been adsorbed is brought into contact with an acid. If the substance (e.g., culture medium) to be contacted with the lactic acid adsorbent of this embodiment contains not only lactic acid but also alkali metals, the alkali metals may be adsorbed to the lactic acid adsorbent of this embodiment together with lactic acid. Depending on the amount of alkali metal adsorbed to the lactic acid adsorbent of this embodiment, not only lactic acid but also the alkali metals may suppress the adsorption of lactic acid. The acid regeneration treatment can remove not only lactic acid adsorbed to the lactic acid adsorbent but also alkali metals (at least a portion of the alkali metals) adsorbed to the lactic acid adsorbent. For this reason, it is preferred to use an acid regeneration treatment for the regeneration treatment.

[0107] In the acid regeneration treatment, the method of contacting the lactic acid adsorbent with the acid is not particularly limited as long as it is a method in which the acid comes into contact with the zeolite contained in the lactic acid adsorbent (the zeolite according to this embodiment), but an example is a method in which the lactic acid adsorbent is mixed with the acid.

[0108] In the acid regeneration treatment, hydrochloric acid can be used as the acid to be contacted with the lactic acid adsorbent. The concentration of hydrochloric acid is optional, but can be, for example, 0.5 mol / L or more and 6 mol / L or less. In the acid regeneration treatment, the contact between the lactic acid adsorbent and the acid may be carried out in the presence of a solvent. Examples of the solvent include at least one of water and alcohol, and water is preferred.

[0109] The conditions for the acid regeneration treatment are not particularly limited as long as they can remove lactic acid from the lactic acid adsorbent. However, the higher the mass ratio of acid to lactic acid adsorbent (hereinafter also referred to as the "acid / lactic acid adsorbent mass ratio"), the easier it is to remove lactic acid; the longer the contact time between the lactic acid adsorbent and the acid (hereinafter also referred to as the "acid contact time"), the easier it is to remove lactic acid; and the higher the contact temperature between the lactic acid adsorbent and the acid (hereinafter also referred to as the "acid contact temperature"), the easier it is to remove lactic acid. Therefore, it is preferable to appropriately adjust the acid / lactic acid adsorbent mass ratio, acid contact time, and acid contact temperature in consideration of the above-mentioned characteristics so as to remove lactic acid. The acid / lactic acid adsorbent mass ratio can be, for example, 0.05 to 3 or 0.08 to 1. The acid contact time can be, for example, 0.05 to 5 hours or 0.08 to 2 hours. The acid contact temperature is, for example, 10°C or higher and 80°C or lower, or 20°C or higher and 50°C or lower.

[0110] The acid-regenerated lactic acid adsorbent may be further subjected to at least one of a washing treatment and a drying treatment. The washing treatment and drying treatment that can be performed on the acid-regenerated lactic acid adsorbent are the same as the washing treatment and drying treatment that can be performed on the acid-treated raw zeolite, respectively, and therefore detailed explanations thereof will be omitted.

[0111] By carrying out the above-described regeneration treatment, the lactic acid adsorbed to the lactic acid adsorbent of this embodiment can be removed. The lactic acid adsorbent of this embodiment exhibits excellent lactic acid adsorption capacity even before the regeneration treatment, and the lactic acid adsorption capacity is not easily reduced even after the regeneration treatment. Therefore, the lactic acid adsorbent of this embodiment is likely to adsorb lactic acid even after the regeneration treatment. Therefore, the lactic acid adsorbent of this embodiment can be easily used repeatedly to adsorb lactic acid.

[0112] The lactic acid adsorption rate of the lactic acid adsorbent of this embodiment is not particularly limited, but the first lactic acid adsorption rate (hereinafter also referred to as "lactic acid adsorption rate (fresh)") is preferably 30% or more and 100% or less, and more preferably 33% or more and 100% or less. Note that the first lactic acid adsorption rate (lactic acid adsorption rate (fresh)) is the lactic acid adsorption rate when the first lactic acid adsorption treatment (the first lactic acid adsorption treatment) is performed.

[0113] Furthermore, the lactic acid adsorbent of this embodiment preferably has a second lactic acid adsorption rate (hereinafter also referred to as "lactic acid adsorption rate (after regeneration)") of 25% or more and 100% or less, and more preferably 28% or more and 100% or less. The second lactic acid adsorption rate (lactic acid adsorption rate (after regeneration)) is the lactic acid adsorption rate when the second lactic acid adsorption treatment is performed after the first regeneration treatment (initial regeneration treatment) to remove the lactic acid adsorbed by the first lactic acid adsorption treatment (initial lactic acid adsorption treatment).

[0114] The lactic acid adsorption rate of the lactic acid adsorbent of this embodiment can be calculated from the following formula (3): X=(Y-Z) / Y×100 (3) In the formula (3), X represents the n-th lactic acid adsorption rate (%), Y represents the lactic acid concentration (mass%) of the test solution before the n-th lactic acid adsorption treatment, and Z represents the lactic acid concentration (mass%) of the test solution after the n-th lactic acid adsorption treatment.

[0115] The lactic acid adsorption treatments (first and second lactic acid adsorption treatments) performed to determine the lactic acid adsorption rate are treatments that can adsorb lactic acid until adsorption equilibrium is reached, and specifically, a container is filled with a basal medium D-MEM (test solution) at pH 7.4 to which a 70% by mass aqueous solution of sodium L-lactate has been added so that the lactic acid concentration is 0.10% by mass, and a lactic acid adsorbent at a mass ratio of 8.33:1 (D-MEM test solution:lactic acid adsorbent), and the container is stirred at 25°C for 17 hours.

[0116] The regeneration treatment carried out to determine the lactic acid adsorption rate (lactic acid adsorption rate (after regeneration)) is a treatment that can remove all of the lactic acid adsorbed to the lactic acid adsorbent. Specifically, this treatment can include mixing the lactic acid adsorbent with 2 mol / L hydrochloric acid and water in a mass ratio of 1:1.25:18.75 (lactic acid adsorbent:hydrochloric acid:water), and stirring at room temperature (25°C) for 5 minutes.

[0117] The lactic acid adsorbent of this embodiment is not particularly limited in terms of the retention rate of lactic acid adsorption capacity (hereinafter also referred to as "performance retention rate"), but it is preferably 60% or more and 100% or less, and more preferably 70% or more and 100% or less. The performance retention rate (%) is an index showing how much lactic acid adsorption capacity is maintained when regenerated, and can be calculated from the following formula (4) using the lactic acid adsorption rate (fresh) (%) and the lactic acid adsorption rate (after regeneration) (%). Performance retention rate = lactic acid adsorption rate (after regeneration) / lactic acid adsorption rate (fresh) × 100 ... (4)

[0118] Next, a lactic acid adsorption device using the lactic acid adsorbent of this embodiment (hereinafter also referred to as the "lactic acid adsorption device of this embodiment") will be described. The lactic acid adsorption device of this embodiment is a device that adsorbs lactic acid contained in a culture medium using the lactic acid adsorbent of this embodiment packed in a column.

[0119] An example of a lactic acid adsorption apparatus of this embodiment is shown in Figure 1. The lactic acid adsorption apparatus 100 of this embodiment shown in Figure 1 includes a culture medium supply tank 1, a first supply pipe 2, an adsorption column 3, a first discharge pipe 4, a regenerated culture medium tank 5, a regenerated liquid tank 6, a second supply pipe 7, a second discharge pipe 8, and a waste liquid tank 9.

[0120] The culture medium supply tank 1 contains a culture medium containing lactic acid and is connected to the adsorption column 3 via a supply pipe 2. For example, the culture medium contained in the culture medium supply tank 1 can be supplied to the adsorption column 3 by driving a pump (not shown) provided on the first supply pipe 2.

[0121] The adsorption column 3 is filled with the lactic acid adsorbent of this embodiment, and the culture medium supplied from the culture medium supply tank 1 passes through the adsorption column 3, allowing the lactic acid contained in the culture medium to be adsorbed by the lactic acid adsorbent. The culture medium passing through the adsorption column 3 is preferably liquid, as this facilitates contact with the zeolite of this embodiment. The adsorption column 3 is connected to a regeneration culture medium tank 3 via a first discharge pipe 4, and the culture medium discharged from the adsorption column 3 (i.e., the culture medium from which at least a portion of the lactic acid has been removed) can be stored in a regeneration culture medium tank 5. Discharge of the culture medium from the adsorption column 3 can be performed, for example, by controlling the opening and closing of an outlet (not shown) of the adsorption column 3 connected to the discharge pipe 4.

[0122] The medium contained in the regenerated medium tank 5 has a reduced amount of lactic acid compared to the medium contained in the medium supply tank 1, and can therefore be reused as a medium. That is, the medium contained in the regenerated medium tank 5 can be used for the above-mentioned cultivation, and the medium in which lactic acid has been regenerated by cultivation can be contained in the medium supply tank 1.

[0123] Here, the medium contained in the regeneration medium tank 5 may be used for the above-described culture as is, or may be used for culture after pH adjustment. The pH adjustment can be performed, for example, by adding a pH adjuster to the medium. The pH adjustment of the medium may be performed in the regeneration medium tank 5, or may be performed in a pH adjustment tank (not shown) provided in the lactic acid adsorption device 100. The pH adjustment tank may be connected to the regeneration medium tank 5, for example, via piping (not shown), so that the medium contained in the regeneration medium tank 5 can flow into it.

[0124] The regenerant tank 6 contains a regenerant liquid (e.g., an acid liquid in the acid regeneration treatment) for performing the above-described regeneration treatment. The regenerant tank 6 is connected to the adsorption column 3 via a second supply pipe 7. For example, the regenerant liquid contained in the regenerant tank 6 can be supplied to the adsorption column 3 by driving a pump (not shown) provided on the second supply pipe 7.

[0125] In the lactic acid adsorption apparatus 100, the culture medium and the regenerated liquid are respectively supplied to the adsorption column 3 by using two supply pipes 2 and 7, but the present invention is not limited to this. For example, by using a branch pipe that branches into three directions, namely, a pipe connected to the culture medium supply tank 1 (a pipe through which the culture medium flows), a pipe connected to the regenerated liquid tank 6 (a pipe through which the regenerated liquid flows), and a pipe connected to the adsorption column 3, and controlling the switching valves provided at the branching points, the culture medium and the regenerated liquid can be supplied to the adsorption column 3 at different times.

[0126] The regenerated liquid supplied from the regenerated liquid tank 6 passes through the inside of the adsorption column 3, whereby the lactic acid adsorbed in the lactic acid adsorbent can be released from the lactic acid adsorbent, thereby restoring the adsorption performance of the lactic acid adsorbent. The timing for supplying the regenerated liquid from the regenerated liquid tank 6 to the adsorption column 3 can be determined as appropriate.

[0127] Lactic acid released from the lactic acid adsorbent is discharged from the adsorption column 3 together with the regenerated liquid, and the discharged mixture of the regenerated liquid and lactic acid (hereinafter also referred to as "waste liquid") moves to a waste liquid tank 9 via a second discharge pipe 8. The discharge of the waste liquid from the adsorption column 3 can be performed by controlling the opening and closing of a discharge port (not shown) of the adsorption column 3 connected to the discharge pipe 8. The waste liquid collected in the waste liquid tank 9 can be discarded at any time.

[0128] In the lactic acid adsorption device 100, the medium is supplied to the regeneration medium tank 5 and the waste liquid is supplied to the waste liquid tank 9 by using two discharge pipes 4 and 8, but this is not limited to this. For example, by using a branch pipe that branches in three directions, namely, a pipe connected to the regeneration medium tank 5 (a pipe through which the medium flows), a pipe connected to the waste liquid tank 9 (a pipe through which the waste liquid flows), and a pipe connected to the adsorption column 3, and controlling a switching valve provided at the branch point, the medium can be supplied to the regeneration medium tank 5 and the waste liquid to the waste liquid tank 9.

[0129] The lactic acid adsorption device 100 may be provided with a measuring instrument (not shown) for measuring the state of the culture medium. Examples of the measuring instrument include a thermometer, a flow meter, and a pH meter, and one or more of these may be used. The measuring instrument may be disposed at any position where the state of the culture medium can be measured, and is not particularly limited. Furthermore, a filter for removing solids may be disposed in the flow path through which the culture medium flows. The filter is preferably disposed upstream of the adsorption column 3 in the direction of flow of the culture medium.

[0130] The lactic acid adsorption device 100 can reduce the amount of lactic acid contained in the culture medium, allowing the culture medium to be recycled. In addition, the lactic acid adsorption device 100 can also remove lactic acid adsorbed to the lactic acid adsorbent, allowing the culture medium to be continuously recycled.

[0131] The lactic acid adsorption device of this embodiment is not limited to the lactic acid adsorption device 100 shown in Fig. 1 as long as it can adsorb lactic acid contained in the culture medium. For example, the lactic acid adsorption device of this embodiment may be a lactic acid adsorption device 200 having a culture medium supply tank 1, a first supply pipe 2, an adsorption column 3, a first discharge pipe 4, and a regenerated culture medium tank 5, as shown in Fig. 2. Even in such a lactic acid adsorption device 200, the culture medium supplied from the culture medium supply tank 1 passes through the adsorption column 3, so that the lactic acid contained in the culture medium is adsorbed by the lactic acid adsorbent, thereby producing a culture medium with a reduced amount of lactic acid.

[0132] Furthermore, although the lactic acid adsorption apparatus 200 shown in FIG. 2 includes a culture medium supply tank 1, the lactic acid adsorption apparatus of this embodiment may or may not include the culture medium supply tank 1. For example, the lactic acid adsorption apparatus of this embodiment may be a lactic acid adsorption apparatus 300, as shown in FIG. 3, which includes a first supply pipe 2, an adsorption column 3, a first discharge pipe 4, and a regenerated culture medium tank 5. In this lactic acid adsorption apparatus 300, a culture medium m containing lactic acid collected outside the lactic acid adsorption apparatus 300 is supplied to the adsorption column 3 via the first supply pipe 2. The supplied culture medium m passes through the adsorption column 3, whereby the lactic acid contained in the culture medium m is adsorbed by the lactic acid adsorbent. Therefore, even with the lactic acid adsorption apparatus 300, a culture medium with a reduced amount of lactic acid can be obtained.

[0133] Furthermore, although the lactic acid adsorption apparatus 200 shown in FIG. 2 includes a regenerated medium tank 5, the lactic acid adsorption apparatus of this embodiment may or may not include the regenerated medium tank 5. For example, the lactic acid adsorption apparatus of this embodiment may be a lactic acid adsorption apparatus 400, as shown in FIG. 4, which includes a medium supply tank 1, a first supply pipe 2, an adsorption column 3, and a first discharge pipe 4. In this lactic acid adsorption apparatus 400, the medium supplied from the medium supply tank 1 passes through the adsorption column 3, whereby the lactic acid contained in the medium is adsorbed by the lactic acid adsorbent, thereby producing a medium M with a reduced amount of lactic acid. The medium M with a reduced amount of lactic acid is discharged to the outside of the lactic acid adsorption apparatus 400 via the first discharge pipe 4 and collected outside the lactic acid adsorption apparatus 400.

[0134] Although the lactic acid adsorption apparatus 200 shown in FIG. 2 includes a medium supply tank 1 and a regenerated medium tank 5, the lactic acid adsorption apparatus of this embodiment may or may not include the medium supply tank 1 and the regenerated medium tank 5. For example, the lactic acid adsorption apparatus of this embodiment may be a lactic acid adsorption apparatus 500, as shown in FIG. 5, including a first supply pipe 2, an adsorption column 3, and a first discharge pipe 4. In this lactic acid adsorption apparatus 500, a medium m containing lactic acid collected outside the lactic acid adsorption apparatus 500 is supplied to the adsorption column 3 via the first supply pipe 2. As the supplied medium passes through the adsorption column 3, the lactic acid contained in the medium m is adsorbed by the lactic acid adsorbent, thereby obtaining a medium M with a reduced amount of lactic acid. The medium M with a reduced amount of lactic acid is discharged to the outside of the lactic acid adsorption apparatus 500 via the first discharge pipe 4 and collected outside the lactic acid adsorption apparatus 500.

[0135] In the lactate adsorption devices 200, 300, 400, and 500 shown in FIGS. 2 to 5, the same components as those in the lactate adsorption device 100 shown in FIG. 1 are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0136] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0137] (Identification of Skeleton Structure) To identify the skeletal structure, a common powder X-ray diffractometer (device name: Ultima IV Protectus, manufactured by Rigaku Corporation) was used to perform XRD measurement of the sample. The measurement conditions were as follows: Acceleration current / voltage: 40 mA / 40 kV Radiation source: CuKα radiation (λ=1.5405 Å) Measurement mode: Continuous scan Scan conditions: 40° / min Measurement range: 2θ=3° to 43° Divergence vertical limiting slit: 10 mm Divergence / entrance slit: 1° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0138] The obtained XRD pattern was subjected to baseline correction and detection and intensity analysis of each XRD peak after correction using the analysis program attached to the measuring device (trade name: IGOR Pro 8, manufactured by WaveMetrics). The skeletal structure of the sample was identified by comparing the corrected XRD pattern with a reference pattern. The following analysis conditions were used. Fitting conditions: Automatic, background refinement Dispersion type pseudo-Voigt function (peak shape) Background removal method: Fitting method Kα2 removal method: Kα1 / Kα2 ratio = 0.497 Smoothing method: B-Spline curve Smoothing conditions: Second-order differential method, σ cut value = 3, χ threshold = 1.5

[0139] (Composition Analysis) The measurement sample was heat-treated in an air atmosphere at 110°C for 30 minutes, and 3 g of the sample was molded into a disk sample with a diameter of 50 mm. The molded sample was measured by X-ray fluorescence analysis (XRF) using a general X-ray fluorescence device (device name: RIX2100, manufactured by Rigaku Corporation). From the obtained measured values ​​of Si, Al, Na, and K, the SiO ２ / Al ２ O ３The Na / Al molar ratio, the Na / Al molar ratio, and the K / Al molar ratio were determined, and the M / Al molar ratio was calculated by adding the Na / Al molar ratio and the K / Al molar ratio. Note that, for Na / Al molar ratios and K / Al molar ratios that were below the lower detection limit, the M / Al molar ratio was calculated by considering the value to be 0.

[0140] In addition, the measured values ​​of each component measured by X-ray fluorescence analysis (XRF) showed that the alumina (Al ２ O ３ ) Each component converted to oxide per 1 mol (SiO ２ , Al ２ O ３ , Na ２ O and K ２ The mass [g] of each component was calculated using the molar mass [g / mol] of each component. ２ O ３ ) Alkali metal element (Na) converted to oxide per 1 mol ２ O and K ２ The mass [g] of the alkali metal element per 1 mol of alumina was calculated by adding up the mass [g] of the alkali metal element per 1 mol of alumina. ２ O ３ ) Each component converted to oxide per 1 mol (SiO ２ , Al ２ O ３ , Na ２ O and K ２ The mass of all the alumina (Al ２ O ３ The mass [g] of the alkali metal element per 1 mol of alumina was defined as the mass (g) of the sample per 1 mol of alumina (Al ２ O ３ The alkali metal content [mass %] was calculated by dividing the mass [g] of the sample per 1 mol of silicon (SiO ２ ), aluminum (Al ２ O ３ ), and alkali metal elements (Na ２ O and K ２The ratio of alkali metal elements (NaO) converted to oxides to the total mass (mass of the sample) of ２ O and K ２ The alkali metal content was determined by calculating the ratio of the total mass of the zeolite and the total amount of sodium ions (0) and expressing this as a percentage. Note that, for components below the lower detection limit, the mass of the component was considered to be 0 [g], and the alkali metal content was determined. In the examples and comparative examples shown below, zeolites containing sodium ions as counter ions in an amount such that the sodium content (ratio of the mass of sodium to the mass of zeolite) exceeds 1.6 mass% were considered to have a sodium-type cation type, and zeolites containing potassium ions in an amount such that the potassium content (ratio of the mass of potassium to the mass of zeolite) exceeds 1.6 mass% were considered to have a potassium-type cation type.

[0141] (Measurement of pH of Zeolite Slurry) 2 g of a measurement sample and 18 g of water were mixed and shaken for 1 minute to obtain a zeolite slurry with a solid content of 10% by mass. The pH of the zeolite slurry at a temperature of 25°C (hereinafter also referred to as "slurry pH") was measured using a common pH meter (device name: F-72S, manufactured by HORIBA), and when the slurry pH was less than 7, it was determined that the cation type of the zeolite was proton type.

[0142] (Analysis of Lactic Acid Concentration) After diluting the sample with 0.1% by mass phosphoric acid aqueous solution, the lactic acid concentration of the sample was measured using a general high-performance liquid chromatography apparatus (apparatus name: UV-8020, manufactured by Tosoh Corporation) equipped with a UV detector under the following conditions: Column: TSKgel ODS-100V (packed silica gel particle size 5 μm, column inner diameter 4.6 mm, column length 25 cm) Eluent: 0.1% by mass phosphoric acid aqueous solution Flow rate: 1.0 mL / min Column temperature: 40°C Injection volume: 10 μL Detection conditions: UV (210 nm) Standard sample: 11.26 mmol / L lactic acid aqueous solution Quantitative method: absolute calibration curve method

[0143] Example 1 48% by mass aqueous solution of sodium hydroxide, amorphous aluminosilicate (SiO ２ / Al ２ O ３A raw material composition having the following molar composition was obtained by mixing SiO (SiO molar ratio: 26.1, Na / Al molar ratio: 1.1) and distilled water. ２ / Al ２ O ３ Molar ratio: 26.1 SDA / Si molar ratio: 0 Na / Si molar ratio: 0.170 K / Si molar ratio: 0 OH / Si molar ratio: 0.170 H ２ O / Si molar ratio: 20.0

[0144] The raw material composition was filled into an 80 mL sealed container and subjected to hydrothermal treatment at 160°C for 72 hours under autogenous pressure while rotating at 55 rpm. The product was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain a raw material zeolite (SiO ２ / Al ２ O ３ molar ratio: 24.8, Na / Al molar ratio: 1.00, K / Al molar ratio: less than 0.001 (below the lower detection limit), alkali metal content (sodium content): 3.75 mass%, cation type: sodium type).

[0145] Next, the raw zeolite, 2 mol / L hydrochloric acid (HCl), and distilled water were mixed so that the mass ratio of hydrochloric acid to the raw zeolite (hereinafter also referred to as the "hydrochloric acid / zeolite mass ratio") was 1.7 and the solid content concentration was 3.0 mass%, and the mixture was stirred for 30 minutes at 25° C. The acid-treated raw zeolite was filtered, washed with pure water, and then dried in an air atmosphere at 110° C. for 15 hours to obtain a zeolite having an MFI-type framework structure and SiO 2 . ２ / Al ２ O ３ A zeolite (crystalline aluminosilicate) having a molar ratio of 25.2, a Na / Al molar ratio of 0.001, a K / Al molar ratio of less than 0.001 (less than the detection limit), a M / Al molar ratio of 0.001, an alkali metal content of 0.004 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this example.

[0146] Example 2 48 mass% sodium hydroxide aqueous solution, amorphous aluminosilicate (SiO ２ / Al ２ O３ A raw material composition having the following molar composition was obtained by mixing SiO (SiO molar ratio: 32.7, Na / Al molar ratio: 1.0) and distilled water. ２ / Al ２ O ３ Molar ratio: 32.7 SDA / Si molar ratio: 0 Na / Si molar ratio: 0.160 K / Si molar ratio: 0 OH / Si molar ratio: 0.160 H ２ O / Si molar ratio: 20.0

[0147] A crystalline silica having an MFI-type skeletal structure and SiO 2 was prepared in the same manner as in Example 1, except that the obtained raw material composition was used instead of the raw material composition used in Example 1. ２ / Al ２ O ３ A zeolite (crystalline aluminosilicate) having a molar ratio of 31.8, a Na / Al molar ratio of less than 0.001 (below the detection limit), a K / Al molar ratio of less than 0.001 (below the detection limit), a M / Al molar ratio of 0.000, an alkali metal content of 0.000 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this example. Note that the raw material zeolite of this example was a zeolite (SiO ２ / Al ２ O ３ molar ratio: 31.5, Na / Al molar ratio: 1.00, K / Al molar ratio: less than 0.001 (less than the lower detection limit), alkali metal content (sodium content): 3.01 mass%, cation type: sodium type).

[0148] Example 3 48 mass% potassium hydroxide aqueous solution, amorphous aluminosilicate (SiO ２ / Al ２ O ３ A raw material composition having the following molar composition was obtained by mixing trans-1,1'-(1,4-cyclohexanediyl)dipyrrolidinium bis(methyl sulfate), 1,1'-(1,4-cyclohexanediyl)dipyrrolidinium bis(methyl sulfate), and distilled water. In the following composition, SDA represents 1,1'-(1,4-cyclohexanediyl)dipiperidinium cation. SiO ２ / Al ２ O ３ Molar ratio: 24.1 SDA / Si molar ratio: 0.05 Na / Si molar ratio: 0.005 K / Si molar ratio: 0.320 OH / Si molar ratio: 0.325 H ２ O / Si molar ratio: 30.0

[0149] The raw material composition was filled into an 80 mL sealed container and subjected to hydrothermal treatment at 170°C for 60 hours under autogenous pressure while rotating at 55 rpm. The product was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain raw zeolite. Next, the raw zeolite was calcined in an air atmosphere consisting of dry air (water content: 1% by volume or less) at 600°C for 2 hours to obtain raw zeolite (SiO ２ / Al ２ O ３ molar ratio: 24.1, Na / Al molar ratio: 0.005, K / Al molar ratio: 0.254, alkali metal content: 1.54 mass% (sodium content: 0.02 mass%, potassium content: 1.52 mass%, cation type: proton type).

[0150] Next, the raw zeolite, ammonium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and distilled water were mixed so that the mass ratio of ammonium chloride to the raw zeolite (hereinafter also referred to as the "ammonium chloride / zeolite mass ratio") was 3 and the solids concentration of the zeolite was 10 mass%, and the mixture was stirred at 50°C for 3 hours. The ammonium-treated raw zeolite was filtered and washed with pure water. These treatments (ammonium treatment and washing treatment) were repeated, with each treatment being performed twice in total. The obtained raw zeolite was dried in an air atmosphere at 110°C for 15 hours, and then calcined in an air atmosphere consisting of dry air (water content: 1% by volume or less) at 550°C for 1 hour, thereby obtaining a zeolite having an MSE-type framework structure and SiO ２ / Al ２ O ３A zeolite (crystalline aluminosilicate) having a molar ratio of 26.7, a Na / Al molar ratio of less than 0.001 (less than the detection limit), a K / Al molar ratio of 0.051, an M / Al molar ratio of 0.051, an alkali metal content of 0.281 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this example.

[0151] Example 4 A 48% by mass aqueous solution of potassium hydroxide, a 35% by mass aqueous solution of tetraethylammonium hydroxide, and an amorphous aluminosilicate (SiO ２ / Al ２ O ３ A raw material composition having the following molar composition was obtained by mixing SiO (SiO 2 , SiO 3 , SiO 4 , SiO 5 , SiO 6 , SiO 7 , SiO 8 , SiO 9 , SiO 10 , SiO 20 , SiO 30 , SiO 40 , SiO 50 , SiO 60 , SiO 20 , SiO 20 , SiO 30 , SiO 2 ... ２ / Al ２ O ３ Molar ratio: 18.2 SDA / Si molar ratio: 0.12 Na / Si molar ratio: 0 K / Si molar ratio: 0.12 OH / Si molar ratio: 0.24 H ２ O / Si molar ratio: 12.0

[0152] Beta zeolite (product name: HSZ (registered trademark)-930NHA, manufactured by Tosoh Corporation) was mixed as seed crystals with the raw material composition so that the seed crystal content was 4.0% by mass. The raw material composition was then filled into an 80 mL sealed container and subjected to hydrothermal treatment at 150°C for 48 hours under autogenous pressure while rotating at 55 rpm. The product was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain raw material zeolite. Next, the raw material zeolite was calcined for 2 hours at 600°C in an air atmosphere consisting of dry air (water content: 1% by volume or less) to obtain raw material zeolite (SiO ２ / Al ２ O ３ molar ratio: 18.0, Na / Al molar ratio: less than 0.001 (below the lower detection limit), K / Al molar ratio: 0.60, alkali metal content (potassium content): 4.56 mass%, cation type: potassium type) was obtained.

[0153] The ammonium treatment, washing treatment, drying treatment, and calcination treatment were carried out in the same manner as in Example 3, except that the raw zeolite used in Example 3 was replaced with the raw zeolite obtained, and the skeletal structure was obtained as beta, SiO ２ / Al ２ O ３ A zeolite (crystalline aluminosilicate) having a molar ratio of 18.1, a Na / Al molar ratio of 0.001, a K / Al molar ratio of 0.026, a M / Al molar ratio of 0.027, an alkali metal content of 0.211 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this example.

[0154] Comparative Example 1 FAU-type zeolite (product name: HSZ (registered trademark)-320HOA, manufactured by Tosoh Corporation, SiO ２ / Al ２ O ３ 35% by mass of hydrochloric acid (molar ratio: 5.7, Na / Al molar ratio: 0.290, K / Al molar ratio: less than 0.001 (less than the lower detection limit), alkali metal content (sodium content): 3.89% by mass, cation type: sodium type) and distilled water were mixed and stirred for 1 hour at 60° C. The zeolite treated with hydrochloric acid was filtered, washed with pure water, and then dried in air at 110° C. for 15 hours.

[0155] Next, zeolite treated with hydrochloric acid to an ammonium chloride / zeolite mass ratio of 1.3 and a solids concentration of 7.3 mass% was mixed with ammonium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and distilled water and stirred at room temperature for 1 hour to obtain a mixture. The resulting mixture was filtered, and the recovered solid was washed with pure water and then dried in air at 110°C for 15 hours. The dried zeolite was heat-treated at 550°C for 1 hour in an atmosphere of steam-mixed air with a moisture content of 25% by volume.

[0156] The steam-treated zeolite, 98% by mass of sulfuric acid, and distilled water were mixed so that the mass ratio of sulfuric acid to zeolite was 0.20 and the solid content concentration was 17% by mass, and the mixture was stirred for 1 hour at 60° C. The zeolite treated with sulfuric acid was filtered, washed with pure water, and then dried in an air atmosphere at 110° C. for 15 hours to obtain a zeolite having an FAU-type framework and SiO ２ / Al ２ O ３ A zeolite (crystalline aluminosilicate) having a molar ratio of 28.4, a Na / Al molar ratio of 0.003, a K / Al molar ratio of less than 0.001 (below the detection limit), a M / Al molar ratio of 0.003, an alkali metal content of 0.010 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this comparative example. Note that FAU-type zeolite has pores with 12-membered oxygen rings with a dimensionality of 3 as pores with 10-membered oxygen rings or more, but does not have pores with 5-membered oxygen rings.

[0157] Comparative Example 2 MOR type zeolite (product name: HSZ (registered trademark)-660HOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. This zeolite has a framework structure of MOR type, SiO ２ / Al ２ O ３ The zeolite (crystalline aluminosilicate) had a molar ratio of 31.2, a Na / Al molar ratio of 0.046, a K / Al molar ratio of less than 0.001 (below the lower detection limit), a M / Al molar ratio of 0.046, an alkali metal content of 0.144 mass%, and a proton-type cation type. Note that MOR-type zeolite has pores with five-membered oxygen rings, but only has pores with one dimensionality and one 12-membered oxygen ring as pores with ten or more membered oxygen rings.

[0158] Comparative Example 3 FER type zeolite (product name: HSZ (registered trademark)-722HOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. This zeolite has a FER type framework structure and SiO ２ / Al ２ O ３The zeolite (crystalline aluminosilicate) had a molar ratio of 18.9, a Na / Al molar ratio of 0.01, a K / Al molar ratio of 0.005, a M / Al molar ratio of 0.015, an alkali metal content of 0.043 mass%, and a proton-type cation type. Note that FER-type zeolite has pores with five-membered oxygen rings, but only has pores with one dimensionality of ten-membered oxygen rings as pores with ten or more membered oxygen rings.

[0159] Comparative Example 4: 48% by mass aqueous solution of sodium hydroxide, 48% by mass aqueous solution of potassium hydroxide, amorphous aluminosilicate (SiO ２ / Al ２ O ３ A raw material composition having the following molar composition was obtained by mixing an aqueous solution of (1-adamantyl)trimethylammonium hydroxide (1-adamantyl)trimethylammonium hydroxide (1-adamantyl)trimethylammonium hydroxide molar ratio: 25.3, Na / Al molar ratio: 0.07) and distilled water. In the following composition, SDA represents (1-adamantyl)trimethylammonium cation. SiO ２ / Al ２ O ３ Molar ratio: 25.3 SDA / Si molar ratio: 0.081 Na / Si molar ratio: 0.084 K / Si molar ratio: 0.084 OH / Si molar ratio: 0.249 H ２ O / Si molar ratio: 18.0

[0160] The raw material composition was filled into an 80 mL sealed container and subjected to hydrothermal treatment at 150°C for 48 hours under autogenous pressure while rotating at 55 rpm. The product was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain zeolite. Next, the zeolite was calcined in an air atmosphere consisting of dry air (water content: 1% by volume or less) at 600°C for 2 hours to obtain zeolite (SiO ) having a CHA-type framework structure. ２ / Al ２ O ３ molar ratio: 24.2, Na / Al molar ratio: 0.050, K / Al molar ratio: 0.180, alkali metal content: 1.27 mass %, cation type: proton type) was obtained.

[0161] The ammonium treatment, washing treatment, drying treatment, and calcination treatment were carried out in the same manner as in Example 3, except that the obtained zeolite was used instead of the raw zeolite used in Example 3. The zeolite was found to have a CHA-type skeletal structure and a SiO ２ / Al ２ O ３ A zeolite (aluminosilicate) having a molar ratio of 24.5, a Na / Al molar ratio of less than 0.001 (less than the detection limit), a K / Al molar ratio of 0.001, an M / Al molar ratio of 0.001, an alkali metal content of 0.006 mass%, and a proton-type cation type was obtained, and this was used as the lactic acid adsorbent of this comparative example. Note that CHA-type zeolite does not have pores with 5-membered oxygen rings or pores with 10 or more-membered oxygen rings.

[0162] Comparative Example 5 The zeolite obtained in Example 1, sodium carbonate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and distilled water were mixed so that the mass ratio of sodium carbonate to the zeolite was 0.032 and the solid content concentration was 28 mass%, and the mixture was stirred for 30 minutes at 25° C. The obtained zeolite was filtered, washed with pure water, and then dried in an air atmosphere at 110° C. for 15 hours to obtain a zeolite having an MFI-type framework and SiO ２ / Al ２ O ３ A zeolite (crystalline aluminosilicate) having a molar ratio of 25.2, a Na / Al molar ratio of 0.441, a K / Al molar ratio of less than 0.001 (below the detection limit), a M / Al molar ratio of 0.441, an alkali metal content of 1.663 mass%, and a sodium cation type was obtained, and this was used as the lactic acid adsorbent of this comparative example.

[0163] [First Lactic Acid Adsorption Treatment] A 70% by mass aqueous solution of sodium L-lactate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added to a basal medium D-MEM (Dulbecco's Modified Eagle's Medium, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 11.3 mmol / L (0.10% by mass) in terms of lactic acid to obtain a test solution (hereinafter also referred to as "D-MEM test solution"). The pH of the D-MEM test solution was 7.4. A 250 mL polypropylene container was filled with 12 g of each adsorbent obtained in the Examples and Comparative Examples and 100 g of the D-MEM test solution. The container was sealed, and the adsorption treatment was carried out by stirring at 150 rpm and 25°C for 17 hours using a container rotation device (device name: Fine benchtop ball mill stand, manufactured by Tokyo Glass Instruments Co., Ltd.). The adsorbent was separated and recovered to obtain the adsorbent after adsorption treatment. Furthermore, the lactic acid concentrations in the D-MEM test solutions before and after the adsorption treatment were measured, and the lactic acid adsorption rate (fresh) was calculated using the following formula (5): Lactic acid adsorption rate (fresh) (%) = (A - B) / A × 100 (5) In the above formula (5), A represents the lactic acid concentration (mass%) in the D-MEM test solution before the adsorption treatment, and B represents the lactic acid concentration (mass%) in the D-MEM test solution after the adsorption treatment.

[0164] [Regeneration Treatment] 12 g of the adsorbent after the first lactic acid adsorption treatment, 15 g of 2 mol / L hydrochloric acid (Kishida Chemical Co., Ltd.) (hydrochloric acid / lactic acid adsorbent mass ratio = 0.088), and 225 g of distilled water were mixed and stirred for 5 minutes at room temperature (25° C.) The resulting zeolite slurry was filtered, washed with pure water, and then dried in the air at 110° C. for 15 hours to obtain a regenerated adsorbent.

[0165] [Second Lactic Acid Adsorption Treatment] The adsorption treatment was carried out in the same manner as the first lactic acid adsorption treatment, except that 8 g of the regenerated adsorbent and 66.64 g of D-MEM test solution were filled into a polypropylene container and the adsorption treatment was carried out, and the lactic acid adsorption rate (after regeneration) was calculated using the following formula (6): Lactic acid adsorption rate (after regeneration) (%) = (C - D) / C × 100 (6) In the above formula (6), C represents the lactic acid concentration (% by mass) of the D-MEM test solution before the adsorption treatment, and D represents the lactic acid concentration (% by mass) of the D-MEM test solution after the adsorption treatment.

[0166] [Calculation of Adsorption Maintenance Rate] The performance maintenance rate was calculated from the formula (4) above using the lactic acid adsorption rate (fresh) calculated from the formula (5) above and the lactic acid adsorption rate (after regeneration) calculated from the formula (6) above.

[0167] The results are shown in Tables 1 and 2.

[0168] From Table 1, it can be seen that the lactic acid adsorption rate (after regeneration) of the adsorbent of the Example was higher than that of the lactic acid adsorbents of Comparative Examples 1 to 4. Furthermore, since the lactic acid adsorption rate (after regeneration) of the adsorbent of the Example was higher than that (fresh) of the adsorbent of Comparative Example 5, it is clear that the lactic acid adsorption rate (after regeneration) of the adsorbent of the Example was higher than that of the lactic acid adsorbent of Comparative Example 5. From these results, it can be seen that the adsorbents of the Example are more likely to adsorb lactic acid even when regenerated after lactic acid adsorption, compared to the adsorbent of the Comparative Example. Therefore, it can be seen that the adsorbents of Examples 1 to 4 are more easily reused than the adsorbent of the Comparative Example.

[0169] The entire contents of the specification, claims and abstract of Japanese Patent Application No. 2024-55304, filed on March 29, 2024, are hereby incorporated by reference as the disclosure of the specification of the present disclosure.

[0170] 100, 200, 300, 400, 500: Lactic acid adsorption device 1: Culture medium supply tank 2: First supply pipe 3: Adsorption column 4: First discharge pipe 5: Regenerated culture medium tank 6: Regenerated liquid tank 7: Second supply pipe 8: Second discharge pipe 9: Waste liquid tank m: Culture medium containing lactic acid M: Culture medium with reduced amount of lactic acid

Claims

1. A lactic acid adsorbent comprising a zeolite having an MSE, MFI, or beta framework structure, an alkali metal content of 1.6% by mass or less, and a proton-type cation type.

2. The lactic acid adsorbent according to claim 1, wherein the molar ratio of alkali metal elements to aluminum in said zeolite is 0.40 or less.

3. SiO of the zeolite ２ / Al ２ O ３ 3. The lactic acid adsorbent according to claim 1, wherein the molar ratio is 10 or more and 45 or less.

4. A method for recycling a culture medium, which comprises contacting the lactic acid adsorbent according to any one of claims 1 to 3 with a culture medium in which lactic acid has been produced by culturing cells, tissues, or microorganisms.

5. A method for producing a culture medium using the recycling method described in claim 4.

6. A lactic acid adsorption device comprising: an adsorption column filled with the lactic acid adsorbent according to any one of claims 1 to 3; a first supply pipe for supplying a culture medium containing lactic acid to said adsorption column; and a first discharge pipe for discharging the culture medium that has passed through said adsorption column.

7. The lactic acid adsorption device according to claim 6, wherein the lactic acid supply device further comprises a culture medium supply tank that stores a culture medium containing lactic acid to be supplied to the adsorption column, and the adsorption column is connected to the culture medium supply tank via the first supply pipe.

8. The lactic acid adsorption device according to claim 6 or 7, wherein the lactic acid supply device further comprises a regeneration medium tank for storing the medium discharged from the adsorption column, and the adsorption column is connected to the regeneration medium tank via the first discharge pipe.

9. The lactic acid supply device further comprises: a second supply pipe for supplying a regenerated liquid to the adsorption column to remove lactic acid adsorbed by the lactic acid adsorbent; a regenerated liquid tank for storing the regenerated liquid to be supplied to the adsorption column; a second discharge pipe for discharging the regenerated liquid that has passed through the adsorption column; and a waste liquid tank for storing the regenerated liquid discharged from the adsorption column; and the adsorption column is connected to the regenerated liquid tank via the second supply pipe and to the waste liquid tank via the second discharge pipe. A lactic acid adsorption device as described in any one of claims 6 to 8.

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