Lactic acid adsorbent

Abstract

To provide at least one of a lactic acid adsorbent that easily adsorbs lactic acid from a medium, a method for recycling a medium using the same, and a method for producing a medium using the same.SOLUTION: A lactic acid adsorbent comprises FAU-type zeolite having a lattice constant of 24.30 Å or more, an alkali metal content in terms of oxide of 1.5 mass% or less, and a cation type which is a proton type.SELECTED DRAWING: None

Description

[Technical Field]

[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. [Background technology]

[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 culture media in which lactic acid has accumulated, and then reuse (recycle) the culture media. 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 lactic acid adsorbents to remove lactic acid from culture media. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2021-74697 Summary of the Invention [Problem to be solved by the invention]

[0006] It is disclosed that the layered double hydroxide of Patent Document 1 exhibits lactic acid adsorption ability in a lactic acid aqueous solution containing glucose. However, as a result of investigations by the inventors of the present disclosure, it was confirmed that although the lactic acid adsorbent of Patent Document 1 exhibits lactic acid adsorption ability in a lactic acid aqueous solution containing glucose, it exhibits almost no lactic acid adsorption ability in a culture medium in which multiple substances other than lactic acid coexist (hereinafter simply referred to as "culture medium").

[0007] The present disclosure aims to provide at least one of a lactic acid adsorbent that easily adsorbs lactic acid from a culture medium, a method for recycling a culture medium using the same, and a method for producing a culture medium using the same. [Means for solving the problem]

[0008] In this disclosure, we have focused on zeolites for adsorbing lactic acid from culture media and have investigated them. As a result, we have found that among FAU-type zeolites with a lattice constant equal to or greater than a predetermined value, FAU-type zeolites with a specific composition are more likely to adsorb lactic acid from culture media containing multiple substances other than lactic acid.

[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 containing FAU-type zeolite having a lattice constant of 24.30 Å or more, an alkali metal content of 1.5 mass% or less in terms of oxide, and a proton-type cation type. [2] The lactic acid adsorbent according to [1], wherein the lattice constant of the FAU zeolite is 24.30 Å or more and 24.50 Å or less. [3] The lactic acid adsorbent according to [1] or [2], wherein the SiO2 / Al2O3 molar ratio of the FAU-type zeolite is 4 or more and 50 or less. [4] A method for recycling a culture medium, comprising contacting the lactic acid adsorbent according to any one of [1] to [3] above with a culture medium containing lactic acid. [5] A method for producing a culture medium using the recycling method described in [4] above. [Effects of the Invention]

[0010] According to the present disclosure, it is possible to provide at least one of a lactic acid adsorbent that easily adsorbs lactic acid from a culture medium, a method for recycling a culture medium using the same, and a method for producing a culture medium using the same. DETAILED DESCRIPTION OF THE INVENTION

[0011] First, the meaning of each term in this specification will be explained.

[0012] 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.

[0013] "Zeolite-like substances" are compounds that have a regular structure in which T atoms are oxygen-mediated, and in which the T atoms contain at least one atom other than a metal or 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.

[0014] The "regular structure in which T atoms are oxygen-mediated (hereinafter also referred to as "skeletal structure")" of a zeolite or zeolite-like substance refers to a skeletal structure identified by the skeletal code (hereinafter also referred to as "skeletal code") established by the Structure Commission of the International Zeolite Association, or a skeletal structure having an intergrowth structure listed on the International Zeolite Association's website, http: / / www.iza-structure.org / databases / (search date: March 8, 2024). For example, an "FAU structure" is a skeletal structure identified by the skeletal code "FAU." The skeletal structure (skeleton code) of each zeolite can be identified, for example, by comparing with the XRD pattern (hereinafter also referred to as "reference pattern") of each structure listed on the website of the Structure Commission of the International Zeolite Association, "Zeolite Framework Types at http: / / www.iza-structure.org / databases / ." In this embodiment, the terms skeletal structure, crystalline structure, and crystalline phase are used interchangeably.

[0015] 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 that have a crystalline XRD peak in their powder X-ray diffraction (hereinafter also referred to as "XRD") pattern are "crystalline aluminosilicates," and those that do not have a crystalline XRD peak are "amorphous aluminosilicates." Note that zeolites whose T atoms are aluminum (Al) and silicon (Si) fall under the category of "crystalline aluminosilicates."

[0016] The "zeolite slurry" is a liquid that contains zeolite and a dispersion medium and has fluidity.

[0017] The "solid content concentration" of the zeolite slurry is the mass proportion of zeolite in the zeolite slurry, and is the concentration calculated by the following formula (1). Solid content concentration (mass%) = (mass of zeolite (g) / mass of zeolite slurry (g)) × 100 (1) The zeolite slurry mass in the above formula (1) is the mass obtained by measuring the mass of the zeolite slurry, and the zeolite mass is the mass of the zeolite slurry obtained by removing the dispersant from the zeolite slurry, which is obtained by treating the solid content obtained by drying the zeolite slurry after measuring the mass of the zeolite slurry at 600°C in the air.

[0018] The XRD pattern for identifying the skeletal structure is measured using CuKα radiation as a radiation source, and the measurement conditions include the following: Acceleration current / voltage: 40mA / 40kV Radiation source: CuKα radiation (λ=1.5405Å) Measurement mode: Continuous scan Scan condition: 40° / min Measurement range: 2θ=3° to 43° Divergence vertical limit slit: 10mm Divergence / entrance slit: 1° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0019] The XRD pattern can be measured using a general powder X-ray diffractometer (e.g., Ultima IV Protectus, manufactured by Rigaku Corporation). The measured XRD pattern can be analyzed using general analysis software (e.g., 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, refine background Dispersive 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

[0020] The composition in this embodiment, such as the molar ratio of silica to alumina (hereinafter also referred to as the "SiO2 / Al2O3 molar ratio") and the alkali metal content in terms of oxide, can be determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES) with a general ICP device (for example, OPTIMA5300DV, manufactured by PerkinElmer). Note that the measurement sample used in ICP-AES can be a sample solution prepared by dissolving a sample (zeolite) heat-treated in air at 600°C for 1 hour in a mixed aqueous solution of hydrofluoric acid and nitric acid.

[0021] The "lattice constant" in this embodiment is a constant representing the length of the axis of a unit lattice constituting FAU zeolite. The "lattice constant" can be determined by a lattice constant measurement method in accordance with ASTM D3942-80 ("Standard Test Method for Determination of the Unit Cell Dimension of a Faujasite-Type Zeolite") using an XRD pattern of FAU zeolite measured to determine the lattice constant. The unit lattice constituting zeolite has three axes (a-axis, b-axis, and c-axis), and a lattice constant (a, b, and c) is determined for each axis. However, since FAU zeolite is a cubic crystal in which the lengths of the three axes of the unit lattice are the same (i.e., a = b = c), the lattice constant of FAU zeolite is determined to be one. The "lattice constant" in this embodiment can be determined on the assumption that FAU zeolite is a cubic crystal (i.e., a = b = c).

[0022] The method for measuring the XRD pattern to determine the lattice constant is the same as the method for measuring the XRD pattern to identify the skeletal structure, except that the following measurement conditions are used. Acceleration current / voltage: 40mA / 40kV Radiation source: CuKα radiation (λ=1.5405Å) Measurement mode: Continuous scan Scan condition: 1° / min Measurement range: 2θ=52° to 60° Divergence vertical limit slit: 5mm Divergence / entrance slit: 2° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0023] Next, the lactic acid adsorbent of this embodiment will be described.

[0024] The lactic acid adsorbent of this embodiment contains FAU zeolite (hereinafter also referred to as "FAU zeolite according to this embodiment"). The FAU zeolite according to this embodiment has a lattice constant of 24.30 Å or more, an alkali metal content in terms of oxide (hereinafter also simply referred to as "alkali metal content") of 1.5 mass% or less, and a proton cation type.

[0025] In the FAU zeolite according to this embodiment, the lattice constant may be 24.30 Å or more, but from the viewpoint of further improving the lactate adsorption capacity in the culture medium, it is preferably 24.30 Å or more and 24.50 Å or less, and more preferably 24.30 Å or more and 24.48 Å or less.

[0026] In the FAU zeolite according to this embodiment, the alkali metal content is 1.5% by mass or less. In other words, in the FAU zeolite according to this embodiment, the alkali metal content is 0% by mass or more and 1.5% by mass or less. An alkali metal content of 0% by mass means that no alkali metal element is contained. In other words, the FAU zeolite according to this embodiment may or may not contain an alkali metal element, but when it contains an alkali metal element, the alkali metal content is 1.5% by mass or less.

[0027] In the FAU zeolite according to this embodiment, the alkali metal content may be 1.5% by mass or less (0% by mass or more and 1.5% by mass or less), but from the viewpoint of further improving the lactate adsorption capacity in the culture medium, it is preferably 1.2% by mass or less (i.e., 0% by mass or more and 1.2% by mass or less), and more preferably 1.0% by mass or less (i.e., 0% by mass or more and 1.0% by mass or less).

[0028] The alkali metal content in this embodiment is the ratio of the mass of alkali metal elements, calculated as oxides, to the mass of the FAU zeolite according to this embodiment. When the FAU zeolite according to this embodiment contains two or more alkali metal elements, the alkali metal content refers to the total content of these two or more alkali metal elements. Furthermore, when calculating the alkali metal content, when the alkali metal elements are calculated as oxides, lithium (Li) may be represented as LiO, sodium (Na) as NaO, potassium (K) as KO, rubidium (Rb) as RbO, and cesium (Cs) as CsO.

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

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

[0031] In the FAU zeolite according to this embodiment, the alkali metal element is preferably contained in a form in which it is supported on the FAU zeolite, and more preferably in a form in which it is supported as a counter ion (hereinafter simply referred to as a "counter ion") for compensating for the charge of the framework structure of the FAU zeolite. In this embodiment, "containing a predetermined element" means that the predetermined element is contained in the FAU zeolite, and the predetermined element may be contained in any state and at any site. On the other hand, "supporting a predetermined element" means that the predetermined element is contained in the FAU zeolite as a component other than T atoms. Examples of the supported form of the predetermined element include a form in which it 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 FAU 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 1.5 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 zeolites containing alkali metal ions in an amount such that the alkali metal content is 1.5 mass % or less. Note that zeolites whose cation type is proton type contain protons (H + ) and alkali metal ions. + ) and alkali metal ions, there are no counterions other than protons (H + ) 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 ( 1 H + ) is not limited to a particular isotope.

[0034] The T atoms (T atoms constituting the framework structure) of the FAU zeolite according to this embodiment may be at least either metal atoms or metalloid atoms, and are not particularly limited, but are preferably composed of aluminum (Al) and silicon (Si) from the viewpoint of further improving the lactate adsorption capacity in the culture medium. In other words, the FAU zeolite according to this embodiment is preferably a crystalline aluminosilicate having an FAU crystal structure.

[0035] From the viewpoint of further improving the lactate adsorption capacity in the culture medium, the SiO2 / Al2O3 molar ratio of the FAU zeolite according to this embodiment is preferably 4 or more, more preferably 5 or more, and even more preferably 5.5 or more. From the viewpoint of further improving the lactate adsorption capacity in the culture medium, the SiO2 / Al2O3 molar ratio of the FAU zeolite according to this embodiment is preferably 50 or less, more preferably 27 or less, and even more preferably 18 or less. The upper and lower limit values ​​of the SiO2 / Al2O3 molar ratio may be any combination of the above-mentioned upper and lower limit values, but from the viewpoint of further improving the lactate adsorption capacity in the culture medium, it is preferably 4 or more and 50 or less, more preferably 5 or more and 27 or less, and even more preferably 5.5 or more and 18 or less.

[0036] The FAU zeolite according to this embodiment can be produced by adjusting at least one of the lattice constant, alkali metal content, and cation type of the FAU zeolite used as a raw material (hereinafter also referred to as "raw zeolite") so that the lattice constant is 24.30 Å or more, the alkali metal content is 1.5 mass% or less, and the cation type is proton type. Commercially available FAU zeolite can be used as the raw material zeolite. Furthermore, when an FAU zeolite having a lattice constant of 24.30 Å or more, an alkali metal content of 1.5 mass% or less, and a proton type cation type is used as the raw material zeolite, it is not necessary to adjust the lattice constant, alkali metal content, and cation type.

[0037] First, a method for adjusting the lattice constant of the raw material zeolite will be described. To adjust the lattice constant of the raw material zeolite, one or more treatments selected from the group consisting of an acid treatment, a steam treatment, and a calcination treatment can be used.

[0038] The acid treatment is a treatment in which a raw material zeolite is brought into contact with an acid. By subjecting the raw material zeolite to the acid treatment, the lattice constant of the raw material zeolite can be reduced compared to that before the acid treatment.

[0039] 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.

[0040] 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 not limited, but can be, for example, 1% by mass or more and 36% by mass or less.

[0041] The acid treatment conditions are not particularly limited as long as they result in a lattice constant of the raw zeolite of 24.30 Å or greater. However, the higher the mass ratio of acid to raw zeolite (hereinafter also referred to as the "acid / zeolite mass ratio"), the lower the lattice constant of the raw zeolite. The longer the contact time between the raw zeolite and the acid (hereinafter also referred to as the "acid contact time"), the lower the lattice constant of the raw zeolite. The higher the contact temperature between the raw zeolite and the acid (hereinafter also referred to as the "acid contact temperature"), the lower the lattice constant of the raw zeolite. Therefore, it is preferable to appropriately adjust the acid / zeolite mass ratio, acid contact time, and acid contact temperature, taking into account the above-mentioned characteristics, so that the lattice constant of the raw zeolite is 24.30 Å or greater. The acid / zeolite mass ratio can be, for example, 0.01 to 1.0, or 0.05 to 0.25. The acid contact time can be, for example, 0.5 to 24 hours, or 1 to 10 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.

[0042] In the acid treatment, raw zeolite may be mixed with water to form a slurry (hereinafter also referred to as "raw zeolite slurry"), and this raw zeolite slurry may be brought into contact with an acid. The solid content of the raw zeolite slurry (raw zeolite content) may be, for example, from 5% to 30% by mass, or from 10% to 20% by mass, relative to 100% by mass of the raw zeolite slurry.

[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 zeolite with pure water. The drying treatment is a treatment for removing moisture adsorbed on the zeolite. The drying conditions are arbitrary as long as moisture can be removed from the zeolite. One example of the drying conditions is drying the zeolite in an air atmosphere at a temperature of 50°C to 200°C for 1 hour to 24 hours.

[0044] Steam treatment is a process in which raw zeolite is heated 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 steam treatment is a gas with a water vapor content (hereinafter also referred to as "moisture content") of 2% by volume or more, and is distinguished from dry gas with a moisture content of less than 2% by volume. The moisture content (volume % of steam) is a calculated value when the gas contained in the steam is assumed to be an ideal gas, and can be determined using equation (2). By subjecting raw zeolite to steam treatment, the lattice constant of the raw zeolite can be reduced compared to that before the steam treatment. 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 steam.

[0045] In this embodiment, the steam used in the steam treatment is preferably air having a moisture content of 2% by volume or more.

[0046] 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.

[0047] The steam treatment conditions are not particularly limited as long as the lattice constant of the raw zeolite is 24.30 Å or greater. However, the higher the moisture content of the steam, the lower the lattice constant of the raw zeolite. The longer the heating time of the raw zeolite in steam (hereinafter also referred to as the "steam heating time"), the lower the lattice constant of the raw zeolite. The higher the heating temperature of the raw zeolite in steam (hereinafter also referred to as the "steam heating temperature"), the lower the lattice constant of the raw zeolite. Therefore, it is preferable to appropriately adjust the moisture content, steam heating time, and steam heating temperature of the steam, taking into account the above-mentioned characteristics, so that the lattice constant of the raw zeolite is 24.30 Å or greater. The moisture content of the steam can be, for example, 3% to 50% by volume, or 5% to 30% by volume. The steam heating time can be, for example, 30 minutes to 5 hours, or 1 hour to 3 hours. The steam heating temperature is, for example, 400°C or higher and 800°C or lower, or 500°C or higher and 700°C or lower.

[0048] The calcination treatment is a treatment for calcining the raw zeolite. The calcination treatment is a treatment for calcining the raw zeolite in a dry gas with a moisture content of less than 2% by volume, and is different from a steam treatment. By performing the calcination treatment on the raw zeolite, the lattice constant of the raw zeolite can be reduced compared to that before the calcination treatment. Examples of the dry gas include one or more gases selected from the group consisting of air, nitrogen, oxygen, helium, and argon, each having a moisture content of less than 2% by volume, and air with a moisture content of less than 2% by volume is preferred.

[0049] The calcination conditions are not particularly limited as long as they result in a lattice constant of the raw zeolite of 24.30 Å or greater. However, the longer the calcination time (hereinafter simply referred to as "calcination time") of the raw zeolite, the smaller the lattice constant of the raw zeolite, and the higher the calcination temperature (hereinafter simply referred to as "calcination temperature") of the raw zeolite, the smaller the lattice constant of the raw zeolite. Therefore, it is preferable to appropriately adjust the calcination time and calcination temperature, taking into account the above-mentioned characteristics, so that the lattice constant of the raw zeolite is 24.30 Å or greater. Examples of calcination times include 0.5 hours to 5 hours, or 1 hour to 3 hours. Examples of calcination temperatures include 400°C to 900°C, or 500°C to 800°C.

[0050] Next, 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.

[0051] The acid treatment is a treatment in which a 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.

[0052] The acid treatment for adjusting the alkali metal content is the same as the acid treatment for adjusting the lattice constant. In other words, by performing an acid treatment on a raw material zeolite, it is possible to adjust not only the lattice constant of the raw material zeolite but also the alkali metal content. Since the acid treatment for adjusting the alkali metal content is the same as the acid treatment for adjusting the lattice constant, a detailed description thereof will be omitted.

[0053] The conditions for the acid treatment to adjust the alkali metal content are not particularly limited as long as the alkali metal content is 1.5% by mass or less, but the alkali metal content of the raw zeolite decreases as the acid / zeolite mass ratio increases, the alkali metal content of the raw zeolite decreases as the acid contact time increases, and the alkali metal content of the raw zeolite decreases 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, taking these characteristics into consideration, so that the alkali metal content of the raw zeolite is 1.5% by mass or less.

[0054] The ammonium treatment is a treatment in which the raw zeolite is brought into contact with a solution containing ammonium cations (hereinafter also referred to as "ammonium solution"). By subjecting the raw zeolite to the ammonium treatment, the alkali metal content of the raw zeolite can be reduced compared to before the ammonium treatment.

[0055] 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.

[0056] 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.

[0057] The conditions for the ammonium treatment are not particularly limited as long as the alkali metal content is 1.5% by mass or less. However, the alkali metal content of the raw zeolite decreases as the content of the ammonium cation source relative to the ammonium solution (hereinafter also referred to as the "ammonium content") 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 content and ammonium contact time, taking these characteristics into consideration, so that the alkali metal content of the raw zeolite is 1.5% by mass or less. The ammonium content can be, for example, from 1% by mass to 30% by mass or from 5% by mass to 20% by mass. The ammonium contact time can be, for example, from 0.1 hours to 24 hours or from 0.2 hours to 3 hours.

[0058] 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, and therefore detailed description thereof will be omitted.

[0059] 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.

[0060] Calcination is a process in which the raw zeolite is calcined. If the raw zeolite has an ammonium cation type, the cation type of the raw zeolite can be changed to a proton type. The ammonium cation type means that the counter ion is an ammonium ion (NH4 + ), but all of the counter ions contained in the zeolite are ammonium ions (NH4 + ), but also means that it is an ammonium ion (NH4 + ) and allows a trace amount of alkali metal ions to be contained as counter ions.

[0061] The calcination treatment for adjusting the cation type is the same as the calcination treatment for adjusting the lattice constant. In other words, if a raw material zeolite whose cation type is ammonium is subjected to the calcination treatment, not only the lattice constant of the raw material zeolite but also the cation type can be adjusted. Note that if a raw material zeolite whose cation type is other than ammonium is subjected to the calcination treatment, the cation type is not adjusted, but the lattice constant of the raw material zeolite is adjusted. Since the calcination treatment for adjusting the cation type is the same as the calcination treatment for adjusting the lattice constant, a detailed description thereof will be omitted.

[0062] The conditions for the calcination treatment for adjusting the cation type are not particularly limited as long as the cation type of the raw material zeolite becomes the proton type, but the longer the calcination time, the more likely the cation type of the raw material zeolite becomes the proton type, and the higher the calcination temperature, the more likely the cation type of the raw material 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 material zeolite becomes the proton type.

[0063] Here, in the calcination 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 calcination 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 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 material zeolite, not only can the alkali metal content of the raw material 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.

[0064] The conditions for the ammonium treatment to change the cation type to the ammonium type are not particularly limited as long as the cation type of the raw material zeolite is changed to the ammonium type, but the higher the ammonium content, the more likely the cation type of the raw material zeolite is to be changed to the ammonium type, and the longer the ammonium contact time, the more likely the cation type of the raw material zeolite is to be changed to the 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 changed to the ammonium type.

[0065] Steam treatment is a process in which raw zeolite is heated in steam. If raw zeolite with an ammonium cation type is subjected to steam treatment, the cation type of the raw zeolite can be converted to a proton cation type.

[0066] The steam treatment for adjusting the cation type is the same as the steam treatment for adjusting the lattice constant. In other words, if a raw material zeolite whose cation type is ammonium is subjected to steam treatment, not only the lattice constant of the raw material zeolite but also the cation type can be adjusted. However, if a raw material zeolite whose cation type is other than ammonium is subjected to steam treatment, the cation type is not adjusted, but the lattice constant of the raw material zeolite is adjusted. Since the steam treatment for adjusting the cation type is the same as the steam treatment for adjusting the lattice constant, a detailed description thereof will be omitted.

[0067] The conditions for the steam treatment for adjusting the cation type are not particularly limited as long as the cation type of the raw material zeolite becomes the proton type, but the longer the heating time, the more likely the cation type of the raw material zeolite becomes the proton type, and the higher the heating temperature, the more likely the cation type of the raw material zeolite becomes the proton type. Therefore, it is preferable to appropriately adjust the heating time and heating temperature in consideration of the above-mentioned characteristics so that the cation type of the raw material zeolite becomes the proton type.

[0068] 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.

[0069] The lactic acid adsorbent of this embodiment may be composed solely of the above-mentioned FAU type zeolite, or may contain other components in addition to the above-mentioned FAU type zeolite. 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 above-mentioned FAU type zeolite, or may further contain, in addition to the above-mentioned FAU type zeolite, one or more selected from the group consisting of a binder, a molding aid, and water.

[0070] 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 the lactate adsorption capacity of the culture medium, 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.

[0071] 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.

[0072] 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 nanofiber; 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; and polyacrylic acid derivatives, and 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 hydroxypropylcellulose.

[0073] 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.

[0074] 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.

[0075] The lactic acid adsorbent of this embodiment contains a binder in addition to the FAU zeolite, which makes it easier to mold the lactic acid adsorbent of this embodiment into a predetermined shape. Furthermore, the lactic acid adsorbent of this embodiment contains a molding aid and water in addition to the FAU zeolite and binder, which 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 FAU zeolite and binder (and optionally 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 irregular.

[0076] 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.

[0077] 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 FAU 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.

[0078] The medium to be brought into contact with the lactic acid adsorbent of this embodiment may be any medium containing lactic acid. However, from the perspective of the Sustainable Development Goals (SDGs), it is preferable to use a medium containing lactic acid produced by culturing cells, tissues, or microorganisms. The cells and tissues cultured in the medium may be of animal origin or cellular origin. Examples of 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.

[0079] Examples of lactic acid to be adsorbed and removed in 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, with L-lactic acid being more preferred. Lactic acid can be classified into neutral (CH3CH(OH)COOH) and anionic (CH3CH(OH)COO - ) and cation (CH3CH(OH)COOH2 + or CH3CH(OH2 + )COOH), and is preferably neutral or anionic. 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.

[0080] 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 depending on 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.

[0081] Examples of the carbon source include carbohydrates such as one or more selected from the group consisting of glucose (D-glucose), maltose, molasses, dextrin, glycerin, and starch.

[0082] Examples of inorganic salts include one or more selected from the group consisting of calcium chloride (CaCl2), copper(II) sulfate (CuSO4), potassium chloride (KCl), magnesium chloride (MgCl2), magnesium sulfate (MgSO4), sodium chloride (NaCl), sodium bicarbonate (NaHCO3), sodium dihydrogen phosphate (NaH2PO4), zinc sulfate (ZnSO4), iron(II) sulfate (FeSO4), iron(II) nitrate (Fe(NO3)2), and iron(III) nitrate (Fe(NO3)3).

[0083] Examples of amino acids 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), although the L-form is preferably used.

[0084] 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.

[0085] 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.

[0086] Examples of growth factors 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).

[0087] 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.

[0088] 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 FAU-type zeolite of this embodiment and the culture medium.

[0089] 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 FAU-type zeolite to be contacted 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.

[0090] Specific examples of the culture medium 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, and 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™ manufactured by Ajinomoto Co., Inc.) for culturing human iPS cells or human ES cells. TM ), and human mesenchymal stem cells (hMSCs) were cultured in a commercially available serum-free medium for hMSCs (e.g., CiMSTM ), a culture medium in which human mesenchymal stem cells or human fetal 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 one or more types of human-derived cells selected from the group consisting of neural progenitor cells, vascular endothelial cells, mesenchymal progenitor cells, cardiomyocytes, skeletal myoblasts, skeletal muscle cells, smooth muscle cells, corneal epithelial cells, corneal endothelial cells, retinal pigment epithelial cells, chondrocytes, and fibroblasts are cultured in an appropriate medium. Furthermore, examples of cell culture media in which non-human 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 (SAFC Biosciences)). TM African green monkey kidney epithelial cells (Vero cells) were cultured in a commercially available serum-free medium for Vero cells (NutriVero Flex10, manufactured by Biological Industries). TM ), or insect cells (e.g., Sf9 cells) cultured in insect cell medium (e.g., IS Sf Insect Culture Medium manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) TM ) can be used as a culture medium.

[0091] 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.

[0092] The FAU zeolite contained in the lactic acid adsorbent of this embodiment tends to lower the pH of the medium, although this depends on the composition of the medium with which it is contacted. Therefore, the amount of the lactic acid adsorbent of this embodiment to be contacted with the medium is preferably set taking into consideration the pH of the medium after contact with the lactic acid adsorbent. The pH of the medium after contact with the lactic acid adsorbent is preferably 3 to 10 inclusive from the viewpoint of suppressing elution of components derived from the lactic acid adsorbent, more preferably 5 to 9 inclusive from the viewpoint of preventing irreversible deterioration of proteins and biopolymers contained in the medium, and even more preferably 6 to 8 inclusive from the viewpoint of suppressing stress effects on cells, tissues, or microorganisms cultured in the medium. Furthermore, the pH change, calculated by subtracting the pH of the medium after removal of lactic acid from the pH of the medium before adsorption of lactic acid, is preferably 0 to 2 inclusive, and more preferably 0 to 1 inclusive from the viewpoint of suppressing stress effects on cells when the medium contains cells or microorganisms.

[0093] 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.

[0094] In the method of contacting a culture medium with a lactic acid adsorbent of this embodiment, a pH adjuster may be added to the culture medium before, during, or after the adsorption treatment to achieve good cell growth. Examples of the pH adjuster include one or more selected from the group consisting of carbon dioxide, carbonic acid, sodium carbonate, sodium bicarbonate, sodium hydroxide, phosphoric acid, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, hydrochloric acid, sulfuric acid, ammonium chloride, and ammonia. To achieve good cell growth, the pH adjuster is preferably added in an amount that adjusts the culture medium pH to between 6 and 8.

[0095] 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.

[0096] 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.

[0097] 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. [Example]

[0098] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0099] (Identification of skeletal structure) To identify the skeletal structure, the sample was subjected to XRD measurement using a general powder X-ray diffractometer (device name: Ultima IV Protectus, manufactured by Rigaku Corporation). The measurement conditions were as follows: Acceleration current / voltage: 40mA / 40kV Radiation source: CuKα radiation (λ=1.5405Å) Measurement mode: Continuous scan Scan condition: 40° / min Measurement range: 2θ=3° to 43° Divergence vertical limit slit: 10mm Divergence / entrance slit: 1° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0100] 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 measurement device (product 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, refine background Dispersive 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

[0101] (Measurement of lattice constant) To measure the lattice constant, a common X-ray diffraction device (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: 40mA / 40kV Radiation source: CuKα radiation (λ=1.5405Å) Measurement mode: Continuous scan Scan condition: 1° / min Measurement range: 2θ=52° to 60° Divergence vertical limit slit: 5mm Divergence / entrance slit: 2° Receiving slit: open Detector: D / teX Ultra Ni filter used

[0102] Using the obtained XRD pattern, the lattice constant (Å) of the measurement sample was determined by a lattice constant measurement method in accordance with ASTM D3942-80 (“Standard Test Method for Determination of the Unit Cell Dimension of a Faujasite-Type Zeolite”).

[0103] (composition analysis) The measurement sample was heat-treated in air at 600°C for 1 hour and then dissolved in a mixed aqueous solution of hydrofluoric acid and nitric acid to prepare a sample solution. The sample solution was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) using a standard ICP instrument (OPTIMA 5300DV, manufactured by PerkinElmer). The SiO2 / Al2O3 molar ratio of the sample was calculated from the measured values ​​of Si and Al. The sodium content (hereinafter also referred to as "Na2O content") and potassium content (hereinafter also referred to as "K2O content") in terms of oxide were calculated from the measured values ​​of Na and K and the mass of the dissolved sample (total mass of dissolved zeolite). In the following examples and comparative examples, zeolites containing sodium ions as counter ions in an amount such that the Na2O content exceeded 1.5% by mass were considered to have a sodium cation type, and zeolites containing potassium ions in an amount such that the K2O content exceeded 1.5% by mass were considered to have a potassium cation type.

[0104] (pH measurement of zeolite slurry) 2 g of the 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 25°C (hereinafter also referred to as "slurry pH") was measured using a common pH meter (device name: F-72S, manufactured by HORIBA Corporation).

[0105] (pH measurement of culture medium) The pH of the medium was confirmed at 25°C using a common pH test paper (Standard pH Test Paper 6.4-8.0 MN90210, manufactured by MACHEREY-NAAGEL).

[0106] (Ion Chromatography) The lactic acid concentration of the sample was measured using an ion chromatograph (device name: IC-2010, manufactured by Tosoh Corporation) under the following conditions. Mobile phase: 7.5mmol / L NaHCO3 aqueous solution +1.1mmol / L Na2CO3 aqueous solution Column: TSKgel SuperIC AZ (4.6 mm I.D. x 15 cm) TSKgelguardcolumnSuperIC AZ (4.6mm I.D. x 1cm) Column temperature: 40℃ Flow rate: 0.8mL / min Injection volume: 30μL

[0107] Example 1 10 g of FAU-type zeolite (product name: HSZ (registered trademark)-320HOA, manufactured by Tosoh Corporation; SiO2 / Al2O3 molar ratio: 5.6, cation type: sodium type, Na2O content: 3.91 mass%, lattice constant: 24.47 Å) was mixed with 70 g of pure water and stirred to obtain a zeolite slurry. Next, the zeolite slurry was mixed with 6.6 g of 35 mass% hydrochloric acid (HCl) so that the mass ratio of hydrochloric acid to zeolite (hereinafter also referred to as the "hydrochloric acid / zeolite mass ratio") was 0.23, and the mixture was stirred at 60°C for 1 hour. The obtained zeolite slurry was filtered, washed with pure water, and then dried in the air at 110°C for 15 hours to obtain an acid-treated zeolite.

[0108] Next, 8 g of the acid-treated zeolite, 100 g of pure water, and 10 g of ammonium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were mixed 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, dried in an air atmosphere at 110°C for 15 hours, and then heat-treated in a steam-mixed air (steam) atmosphere with a water content of 25% by volume at 550°C for 1 hour to obtain FAU-type zeolite (aluminosilicate) with a proton-type cation type, an Na2O content (alkali metal content) of 0.07% by mass, a lattice constant of 24.37 Å, a SiO2 / Al2O3 molar ratio of 11.1, and a slurry pH of 6.1, which was used as the lactic acid adsorbent of this example.

[0109] Example 2 FAU-type zeolite (product name: HSZ (registered trademark)-341NHA, manufactured by Tosoh Corporation; SiO2 / Al2O3 molar ratio: 7.3, cation type: ammonium type, Na2O content: 0.08 mass%, lattice constant: 24.51 Å) was calcined in a dry air atmosphere at 550°C for 2 hours to obtain FAU-type zeolite (aluminosilicate) with a proton-type cation type, an Na2O content (alkali metal content) of 0.07 mass%, a lattice constant of 24.44 Å, and an SiO2 / Al2O3 molar ratio of 7.3, which was used as the lactic acid adsorbent of this example.

[0110] Example 3 An FAU-type zeolite (aluminosilicate) having a proton-type cation type, an NaO content (alkali metal content) of 0.93 mass%, a lattice constant of 24.42 Å, a SiO / AlO molar ratio of 9.2, and a slurry pH of 6.3 was obtained in the same manner as in Example 1, except that the zeolite slurry was mixed with 5.1 g of 35 mass% hydrochloric acid so that the hydrochloric acid / zeolite mass ratio was 0.18, and this was used as the lactic acid adsorbent of this example.

[0111] Example 4 The zeolite of Example 1 was subjected to heat treatment at 700°C for 2 hours in an atmosphere of steam-mixed air with a water content of 22% by volume to obtain FAU-type zeolite (aluminosilicate) having a proton cation type, an NaO content of 0.07% by mass, a lattice constant of 24.30 Å, and an SiO / AlO molar ratio of 11.1, which was used as the lactic acid adsorbent of this example.

[0112] Example 5 10 g of FAU-type zeolite (product name: HSZ®-320HOA, manufactured by Tosoh Corporation; SiO / AlO molar ratio: 5.6, cation type: sodium type, NaO content: 3.91% by mass, lattice constant: 24.47 Å), 150 g of pure water, and 30 g of ammonium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were mixed and stirred at room temperature for 20 minutes to obtain a mixture. The resulting mixture was filtered, and the recovered solid was washed with pure water, dried in an air atmosphere at 110°C for 15 hours, and then calcined in a dry air atmosphere (water content: 1% by volume or less) at 550°C for 1 hour to obtain FAU-type zeolite (aluminosilicate) with a proton-type cation type, NaO content (alkali metal content) of 0.66% by mass, a lattice constant of 24.46 Å, and a SiO / AlO molar ratio of 5.6. This was used as the lactic acid adsorbent of this example.

[0113] Comparative Example 1 FAU-type zeolite (product name: HSZ (registered trademark)-320HOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. The zeolite was an FAU-type zeolite (aluminosilicate) with a sodium cation type, an NaO content (alkali metal content) of 3.91 mass%, a lattice constant of 24.47 Å, a SiO / AlO molar ratio of 5.6, and a slurry pH of 9.0.

[0114] Comparative Example 2 5 g of the lactic acid adsorbent of Example 1, 100 g of pure water, and 20 g of sodium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added and stirred for 1 hour at 60°C to obtain a zeolite slurry. The obtained zeolite slurry was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain an FAU-type zeolite (aluminosilicate) having a sodium cation type, an Na2O content (alkali metal content) of 1.54 mass%, a lattice constant of 24.38 Å, and a SiO2 / Al2O3 molar ratio of 12.1, which was used as the lactic acid adsorbent of this comparative example.

[0115] Comparative Example 3 5 g of the zeolite of Example 1, 100 g of pure water, and 20 g of ammonium chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added and stirred for 1 hour at 60°C to obtain a zeolite slurry. The obtained zeolite slurry was filtered, washed with pure water, and then dried in air at 110°C for 15 hours to obtain an FAU-type zeolite (aluminosilicate) having an ammonium cation type, an NaO content (alkali metal content) of 0.01 mass%, a lattice constant of 24.38 Å, and an SiO / AlO molar ratio of 12.3, which was used as the lactic acid adsorbent of this comparative example.

[0116] Comparative Example 4 An acid-treated zeolite was obtained in the same manner as in Example 1, except that the zeolite slurry was mixed with 8.6 g of 35% by mass hydrochloric acid to achieve a hydrochloric acid / zeolite mass ratio of 0.30. Also, in the same manner as in Example 1, 8 g of the acid-treated zeolite, 100 g of pure water, and 10 g of ammonium chloride were mixed and stirred at room temperature for 1 hour to obtain a mixture. The resulting mixture was filtered and washed with pure water, then dried in an air atmosphere at 110°C for 15 hours, and then heat-treated at 800°C for 2 hours in an air-steam atmosphere with a water content of 50% by volume. The steam-treated mixture was an FAU-type zeolite (aluminosilicate) with a proton-type cation type, a NaO content (alkali metal content) of 0.06% by mass, a lattice constant of 24.25 Å, a SiO / AlO molar ratio of 14.7, and a slurry pH of 6.2, and was used as the lactic acid adsorbent for this comparison.

[0117] Comparative Example 5 FAU-type zeolite (product name: HSZ (registered trademark)-341NHA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. The zeolite was an FAU-type zeolite (aluminosilicate) with an ammonium cation type, an NaO content (alkali metal content) of 0.08 mass%, a lattice constant of 24.51 Å, a SiO / AlO molar ratio of 7.3, and a slurry pH of 7.1.

[0118] Comparative Example 6 FAU-type zeolite (product name: HSZ (registered trademark)-390HUA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. The zeolite was an FAU-type zeolite (aluminosilicate) with a proton-type cation type, a NaO content (alkali metal content) of less than 0.01% by mass (below the detection limit), a lattice constant of 24.26 Å, a SiO / AlO molar ratio of 770, and a slurry pH of 4.9.

[0119] Comparative Example 7 MFI zeolite (product name: HSZ (registered trademark)-893HOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent of this comparative example. The zeolite was an MFI zeolite (aluminosilicate) with a proton cation type, an NaO content (alkali metal content) of less than 0.01% by mass (below the lower detection limit), an SiO / AlO molar ratio of 2120, and a slurry pH of 4.7. Note that, unlike FAU zeolite, MFI zeolite is not a cubic crystal, and therefore the lattice constant in this embodiment (lattice constant assuming a = b = c) could not be determined.

[0120] Comparative Example 8 Zeolite beta (product name: HSZ (registered trademark)-930NHA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent of this comparative example. This zeolite was zeolite beta (aluminosilicate) with an ammonium cation type, an NaO content (alkali metal content) of 0.04 mass%, and an SiO / AlO molar ratio of 27.0. Unlike FAU-type zeolite, zeolite beta is not a cubic crystal, and therefore the lattice constant (lattice constant assuming a = b = c) in this embodiment could not be determined.

[0121] Comparative Example 9 Zeolite beta (product name: HSZ (registered trademark)-980HOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent in this comparative example. This zeolite was aluminosilicate with a proton-type cation type, a NaO content (alkali metal content) of less than 0.01% by mass (below the detection limit), and an SiO / AlO ratio of 580.

[0122] Comparative Example 10 Layered double hydroxide (product name: Kyoward (registered trademark) 500SH, manufactured by Kyowa Chemical Industry Co., Ltd.); synthetic hydrotalcite (Mg 1-x Al x (OH)2(CO3) x / 2 ·mH2O) was used as the lactic acid adsorbent of this comparative example.

[0123] Comparative Example 11 150 g of the zeolite of Example 1 was mixed with 720 g of pure water and stirred to obtain a zeolite slurry. Next, the zeolite slurry was mixed with 30 g of 98% by mass sulfuric acid (H2SO4) and stirred at 60°C for 1 hour. The obtained zeolite slurry was filtered, washed with pure water, and then dried in an air atmosphere at 110°C for 15 hours to obtain an FAU-type zeolite having a proton cation type, an alkali metal Na2O content of 0.01% by mass, a lattice constant of 24.29 Å, a SiO2 / Al2O3 molar ratio of 28.4, and a slurry pH of 3.3. This was used as the lactic acid adsorbent of this comparative example.

[0124] Comparative Example 12 LTL zeolite (product name: HSZ (registered trademark)-500KOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent of this comparative example. This zeolite was an LTL zeolite (aluminosilicate) with a potassium cation type, a K2O content of 16.5 mass%, a Na2O content of 0.22 mass%, an alkali metal content of 16.7 mass%, a SiO2 / Al2O3 molar ratio of 6.3, and a slurry pH of 10.8. Note that, unlike FAU zeolite, LTL zeolite is not a cubic crystal, and therefore the lattice constant in this embodiment (lattice constant assuming a = b = c) could not be determined.

[0125] Comparative Example 13 FER-type zeolite (product name: HSZ (registered trademark)-720KOA, manufactured by Tosoh Corporation) was used as the lactic acid adsorbent of this comparative example. This zeolite was FER-type zeolite (aluminosilicate) with a potassium cation type, a K2O content of 5.3 mass%, a Na2O content of 1.4 mass%, an alkali metal content of 6.7 mass%, a SiO2 / Al2O3 molar ratio of 18.0, and a slurry pH of 9.9. Note that, unlike FAU-type zeolite, FER-type zeolite is not a cubic crystal, and therefore the lattice constant in this embodiment (a lattice constant assuming a = b = c) could not be determined.

[0126] Measurement example 1 A test solution (hereinafter also referred to as "D-MEM test solution") was obtained by adding sodium L-lactate (Sigma-Aldrich) to a basal medium (D-MEM, Dulbecco's modified Eagle's medium, high glucose, L-glutamine, phenol red-containing, Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 0.10% by mass (as sodium lactate). The pH of the D-MEM test solution was 7.4. 100 mg of each adsorbent obtained in the Examples and Comparative Examples and 2.5 g of the D-MEM test solution were filled into a 4 mL sample tube. The sample tube was sealed and stirred at 100 rpm at 37°C for 24 hours to perform an adsorption treatment. After separating and recovering the adsorbent, the pH of the medium after adsorption and removal of lactate was measured. The lactate concentration was measured by ion chromatography, and the lactate adsorption rate was calculated using the following formula (3). Lactic acid adsorption rate (%)=(AB) / A×100 (3) In the above formula (3), A represents the lactic acid concentration (mass %) of the D-MEM test solution before the adsorption treatment, and B represents the lactic acid concentration (mass %) of the D-MEM test solution after the adsorption treatment.

[0127] [Table 1]

[0128] From Table 1, it can be seen that the adsorbents of the Examples have a higher lactic acid adsorption rate than the adsorbents of the Comparative Examples. From this, it can be seen that the adsorbents of the Examples adsorb lactic acid from culture media more easily than the adsorbents of the Comparative Examples. Furthermore, it can be seen that the adsorbents of the Examples can adsorb lactic acid from culture media, and therefore the culture media can be reused for culturing cells, tissues, or microorganisms.

Claims

1. A lactic acid adsorbent comprising an FAU-type zeolite having a lattice constant of 24.30 Å or more, an alkali metal content of 1.5 mass% or less in terms of oxide, and a proton-type cation type.

2. 2. The lactic acid adsorbent according to claim 1, wherein the lattice constant of the FAU-type zeolite is 24.30 Å or more and 24.50 Å or less.

3. The SiO of the FAU-type zeolite ２ / Al ２ O ３ 2. The lactic acid adsorbent according to claim 1, wherein the molar ratio is 4 or more and 50 or less.

4. A method for recycling a culture medium, comprising contacting the lactic acid adsorbent according to any one of claims 1 to 3 with a culture medium containing lactic acid.

5. A method for producing a culture medium, using the recycling method according to claim 4.

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