REFINING METHOD
A refining method according to the present invention is a refining method for crystallizing a compound with at least one crystal form, including setting, as a target wavelength and a target concentration, a specific infrared wavelength and a specific concentration at which a specific crystal form precipitates from a solution of the compound dissolved in a solvent, and using an infrared radiation apparatus capable of emitting infrared radiation including the target wavelength to evaporate the solvent and precipitate the specific crystal form while irradiating a solution of the compound dissolved in the solvent at the target concentration with infrared radiation including the target wavelength.
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The present invention relates to a refining method.
2. Description of the Related ArtDistillation, recrystallization, chromatography, extraction, and the like are generally known as methods for refining a target organic compound. Patent Literature 1 discloses a method for refining an organic compound using a laser beam. In Patent Literature 1, to selectively produce a metastable substance from a solution of a substance containing a stable form and a metastable form as crystal forms, metastable crystals are selectively produced by emitting a laser beam into the solution to generate bubbles and form metastable crystal nuclei.
CITATION LIST Patent LiteraturePTL 1: Japanese Unexamined Patent Application Publication No. 2014-189462
SUMMARY OF THE INVENTIONIn Patent Literature 1, however, the laser beam is emitted to generate bubbles in the solution, and no attention is paid to light of an infrared absorption wavelength.
The present invention has been made to address such an issue and mainly aims to obtain a specific crystal form from a solution of a compound dissolved in a solvent.
A refining method according to the present invention is a refining method for crystallizing a compound with at least one crystal form, including: setting, as a target wavelength and a target concentration, a specific infrared wavelength and a specific concentration at which a specific crystal form precipitates from a solution of the compound dissolved in a solvent, and using an infrared radiation apparatus capable of emitting infrared radiation including the target wavelength to evaporate the solvent and precipitate the specific crystal form while irradiating a solution of the compound dissolved in the solvent at the target concentration with infrared radiation including the target wavelength.
This refining method can precipitate a specific crystal form from a solution of a compound dissolved in a solvent by adjusting the solvent for dissolving the compound, the infrared radiation emitted to the solution, and the concentration of the compound in the solution. The reason why a specific crystal form precipitates is not clear but is considered as described below. A compound with a plurality of crystal forms generally has a dissolution rate depending on the type of solvent. The dissolution rate is probably related to the ease of precipitation of crystals. Furthermore, a crystal form with higher infrared absorptivity probably has more active thermal vibrations and fewer crystal nuclei. Furthermore, the crystal form precipitated from the solution also depends on the concentration of the compound in the solution. It is therefore thought that the suitable conditions for precipitation of a specific crystal form depend on the solvent for dissolving the compound, the infrared radiation emitted to the solution, and the concentration of the compound in the solution.
Preferred embodiments of the invention are described in detail below.
A refining method according to the present embodiment is a refining method for crystallizing a compound with at least one crystal form, including: setting, as a target wavelength and a target concentration, a specific infrared wavelength and a specific concentration at which a specific crystal form precipitates from a solution of the compound dissolved in a solvent, and using an infrared radiation apparatus capable of emitting infrared radiation including the target wavelength to evaporate the solvent and precipitate the specific crystal form while irradiating a solution of the compound dissolved in the solvent at the target concentration with infrared radiation including the target wavelength.
The compound may have a plurality of crystal forms or a single crystal form.
In one example described below, a specific crystal form is precipitated by evaporating a solvent from a solution of a raw material of an organic compound X with two crystal forms a1 and a2 dissolved in the solvent. The specific crystal form is precipitated on the basis of the results of preliminary experiments. In a first preliminary experiment, it is assumed that a crystal form a1 is precipitated when a solution of the raw material of the organic compound X dissolved in a solvent p1 at a specific concentration C1 [mg/mL] is irradiated with infrared radiation including a wavelength λ1 [µm] (for example, infrared radiation having a peak at the wavelength λ1) to evaporate the solvent p1. In a second preliminary experiment, it is assumed that a crystal form a2 is precipitated when a solution of the raw material of the organic compound X dissolved in the solvent p1 at a specific concentration C2 [mg/mL] is irradiated with infrared radiation including the wavelength λ1 [µm] to evaporate the solvent p1. In such a preliminary experiment, to precipitate the crystal form a1, the solvent p1 used in the first preliminary experiment, infrared radiation including the wavelength λ1 [µm] , and the concentration C1 of the compound in the solution [mg/mL] are employed. To precipitate the crystal form a2, the solvent p1 used in the second preliminary experiment, infrared radiation including the wavelength λ1 [µm] , and the concentration C2 of the compound in the solution [mg/mL] are employed. Although different crystal forms are prepared by changing the concentration of the compound in the solution with the same solvent at the same wavelength in this embodiment, the present invention is not limited to the embodiment. Different crystal forms may be prepared by appropriately changing the combination of solvent, wavelength, and compound concentration. For example, different crystal forms may be prepared by changing the solvent at the same wavelength and at the same compound concentration. Alternatively, different crystal forms may be prepared by changing the wavelength with the same solvent at the same compound concentration.
The wavelength λ1 [µm] is preferably determined on the basis of an infrared absorption spectrum of a crystal form and the dissolution rate of a raw material in a solvent. Crystal forms often have different infrared absorption spectra and often have different absorptivities at a given wavelength. It is thought that when a solution is irradiated with infrared radiation including a certain wavelength, a crystal form with a higher absorptivity at the wavelength has more active thermal vibration than crystal forms with a lower absorptivity, has fewer crystal nuclei, and is less likely to precipitate. On the other hand, it is thought that a crystal form that can easily form crystal nuclei is different between a solvent with a high dissolution rate of a raw material and a solvent with a low dissolution rate of a raw material. Thus, the wavelength λ1 [µm] is preferably determined on the basis of an infrared absorption spectrum of a crystal form and the dissolution rate of a raw material in a solvent. For example, the infrared radiation including the wavelength λ1 [µm] may be infrared radiation having a peak at the wavelength λ1 [µm] .
In the following example, a crystal form c is precipitated by evaporating a solvent q from a solution of an organic compound Y with the crystal form c dissolved in the solvent q. It is assumed that, in a preliminary experiment, the crystal form c precipitates when the solvent q is evaporated while the solution of the organic compound Y dissolved in the solvent q at a concentration c1 [mg/mL] is irradiated with infrared radiation including a wavelength α [µm]. It is also assumed that the crystal form c does not precipitate and is amorphous when the solvent q is evaporated while the solution of the organic compound Y dissolved in the solvent q at a concentration c2 [mg/mL] is irradiated with infrared radiation including the wavelength α [µm]. In such a case, to precipitate the crystal form c, the solvent q may be evaporated while the solution of the organic compound Y dissolved in the solvent q at a concentration c1 [mg/mL] is irradiated with infrared radiation including the wavelength α [µm]. For example, the infrared radiation including the wavelength α [µm] may be infrared radiation having a peak at the wavelength α [µm] .
Examples of compounds that can be refined by the refining method according to the present embodiment include, but are not limited to, febuxostat, terfenadine, indomethacin, ibuprofen, loxoprofen, caffeine, diclofenac, and carbamazepine. Examples of the solvent for dissolving a raw material of a compound include, but are not limited to, alcohol solvents, such as methanol, ethanol, 1-propanol, 2-propanol (isopropanol (IPA)), 1-butanol, 2-butanol, isobutanol, and tert-butanol; nitrile solvents, such as acetonitrile and propionitrile; ether solvents, such as diethyl ether and tetrahydrofuran; ketone solvents, such as acetone and methyl ethyl ketone; halogen solvents, such as dichloromethane and chloroform; ester solvents, such as ethyl acetate and methyl acetate; aliphatic hydrocarbon solvents, such as pentane, hexane, heptane, octane, and cyclohexane; aromatic hydrocarbon solvents, such as benzene, toluene, and xylene; and mixed solvents of alcohol solvents and water.
In the refining method according to the present embodiment, any infrared radiation apparatus capable of emitting infrared radiation including a wavelength λ [µm] can be used. For example, the infrared radiation apparatus may include a sheet radiator and a planar heater serving as a heat source. The infrared radiation apparatus is preferably an infrared radiation apparatus capable of emitting infrared radiation having a peak at the wavelength λ [µm], particularly infrared radiation having a peak at the wavelength λ [µm] and having a narrow half-width. Examples of such an infrared radiation apparatus include metamaterial emitters and infrared radiation apparatuses with a filter. Examples of the metamaterial emitters include emitters of a Metal-Insulator-Metal (MIM) type, a microcavity type, a meta-atom type, and a multilayer type. Examples of the MIM type include those described in Reference 1 (JSME TED Newsletter, No. 74, pp. 7-10, 2014). The MIM type is described in detail later. Examples of the microcavity type and the meta-atom type include those described in Reference 2 (JSME TED Newsletter, No. 74, pp. 2-6, 2014). Examples of the multilayer type include those described in Reference 3 (ACS Cent. Sci., Vol. 5, pp. 319-326, 2019). Examples of the infrared radiation apparatuses with a filter include infrared heaters described in Japanese Patent No. 6442355.
The refining apparatus 1 is an apparatus for precipitating a specific crystal form from a solution 22 in a flat laboratory dish 20 using the infrared heater 10. The solution 22 contains a compound with a plurality of crystal forms dissolved in a solvent.
The infrared heater 10 is an example of a metamaterial emitter of the MIM type and includes a heater body 11, a structure 30, and a casing 70. The infrared heater 10 emits infrared radiation to the solution 22 in the flat laboratory dish 20 located under the infrared heater 10.
The heater body 11 is configured as a planar heater and includes a heating element 12 in which a linear member is bent in a zigzag, and a protective member 13, which is an insulator in contact with and surrounding the heating element 12. The material of the heating element 12 is, for example, W, Mo, Ta, an Fe—Cr—Al alloy, or a Ni—Cr alloy. The material of the protective member 13 is, for example, an insulating resin, such as a polyimide, or a ceramic. The heater body 11 is located inside the casing 70. Both ends of the heating element 12 are coupled to a pair of input terminals (not shown) attached to the casing 70. Electric power can be supplied to the heating element 12 from the outside through the pair of input terminals. The heater body 11 may be a planar heater with a ribbon-like heating element wound around an insulator.
The structure 30 is a sheet radiator provided under the heating element 12. The structure 30 includes a first conductor layer 31 (a metal pattern), a dielectric layer 34, a second conductor layer 35 (a metal substrate), and a supporting substrate 37 stacked in this order from the outside to the inside under the infrared heater 10. The structure 30 is located so as to close an opening in the lower portion of the casing 70.
As illustrated in
The dielectric layer 34 is a flat member with an upper surface bonded to the second conductor layer 35. The dielectric layer 34 is located between the first conductor layer 31 and the second conductor layer 35. A portion of the lower surface of the dielectric layer 34 on which the metal electrodes 32 are not located is a radiation surface 38 for emitting infrared radiation to an object. The material of the dielectric layer 34 is, for example, alumina (Al2O3) or silica (SiO2) .
The second conductor layer 35 is a metal sheet with an upper surface bonded to the supporting substrate 37 via an adhesive layer (not shown). The material of the second conductor layer 35 may be the same as the material of the first conductor layer 31. The material of the adhesive layer is, for example, chromium (Cr), titanium (Ti), or ruthenium (Ru).
The supporting substrate 37 is a flat member fixed inside the casing 70 with a fixing component or the like (not shown) and supports the first conductor layer 31, the dielectric layer 34, and the second conductor layer 35. The material of the supporting substrate 37 is, for example, a material, such as a Si wafer or glass, that can easily maintain a smooth surface, has high heat resistance, and has low thermal warping. The supporting substrate 37 may be in contact with the lower surface of the heater body 11 or may be separated from the lower surface with a space therebetween. When the supporting substrate 37 is in contact with the heater body 11, they may be bonded together.
The structure 30 functions as a metamaterial emitter with the characteristics of selectively emitting infrared radiation of a specific wavelength. The characteristics probably result from a resonance phenomenon explained by magnetic polariton. The magnetic polariton is a resonance phenomenon in which a confinement effect of a strong electromagnetic field can be produced in a dielectric (the dielectric layer 34) between two upper and lower conductors (the first conductor layer 31 and the second conductor layer 35). Thus, in the structure 30, a portion of the dielectric layer 34 between the second conductor layer 35 and the metal electrodes 32 serves as an infrared radiation source. Infrared radiation emitted from the radiation source goes around the metal electrodes 32 and is emitted to the surrounding environment from a portion of the dielectric layer 34 on which the metal electrodes 32 are not located (that is, from the radiation surface 38). In the structure 30, the materials of the first conductor layer 31, the dielectric layer 34, and the second conductor layer 35 and the shape and periodic structure of the first conductor layer 31 can be adjusted to regulate the resonance wavelength. Thus, infrared radiation emitted from the radiation surface 38 of the structure 30 characteristically has high emissivity at a specific wavelength. In the present embodiment, the material, shape, periodic structure, and the like are adjusted so that the structure 30 characteristically emits from the radiation surface 38 infrared radiation having a maximum peak with a half-width of 2.0 µm or less (preferably 1.5 µm or less, more preferably 1.0 µm or less) and with an emissivity of 0.7 or more (preferably 0.8 or more) in the wavelength range of 0.9 to 25 µm (preferably 2.5 to 25 µm (4000 to 400 cm-1) ). Thus, the structure 30 characteristically emits infrared radiation having a sharp maximum peak with a relatively small half-width and a relatively high emissivity. The half-width is, for example, but not limited to, preferably 2.0 µm or less, more preferably 1.5 µm or less, still more preferably 1.0 µm or less.
The casing 70 has an approximately rectangular parallelepiped shape with a space therein and with an open bottom surface. The heater body 11 and the structure 30 are located in the space inside the casing 70. The casing 70 is formed of a metal (for example, stainless steel or aluminum) to reflect infrared radiation emitted from the heating element 12.
An example of use of the refining apparatus 1 is described below. In the following example, as a specific crystal form precipitated from a solution of the organic compound X with two crystal forms a1 and a2 dissolved in a solvent, as described above, the crystal form a1 is precipitated.
First, the flat laboratory dish 20 containing the solution 22 is placed under the first conductor layer 31 of the infrared heater 10. The solution 22 contains the organic compound X dissolved in the solvent p1 at the concentration C1 [mg/mL]. Next, electric power is supplied from a power supply (not shown) through an input terminal to both ends of the heating element 12. The electric power is supplied so that the temperature of the heating element 12 reaches a preset temperature (for example, but not limited to, several hundred degrees Celsius). The heating element 12 heated to the predetermined temperature transfers energy to the surroundings by at least one of three heat transfer modes of conduction, convection, and radiation and heats the structure 30. Consequently, the structure 30 is heated to a predetermined temperature, becomes a secondary radiator, and emits infrared radiation.
In this case, a predetermined wavelength λ1 [µm] is set as a target wavelength, and infrared radiation having a peak at the wavelength λ1 [µm] is set to be emitted from the structure 30. More specifically, the intervals D1 and D2 of the metal electrodes 32 of the structure 30, the widths W1 and W2 of the metal electrodes 32, and the periods Λ1 and Λ2 of the metal pattern are set so that infrared radiation emitted from the structure 30 has a peak at a predetermined wavelength λ1 [µm] . Irradiation of the solution 22 in the flat laboratory dish 20 with infrared radiation having a peak at the wavelength λ1 [µm] evaporates the solvent p1 of the solution 22 with the passage of time and finally selectively precipitates crystals of the organic compound X with the crystal form a1.
Although the infrared heater 10 is designed to mainly emit infrared radiation of a target wavelength, it is difficult to remove all radiation other than the target wavelength from the infrared radiation of the structure 30, and convective heat dissipation from components of the heater to the surroundings will occur in the atmosphere. To form an actual process, therefore, various considerations should be given to the shape of the apparatus and the like so that such associated heat flow does not excessively increase the temperature of raw materials and the like.
The refining method according to the present embodiment described in detail above can precipitate a specific crystal form from a solution of a compound dissolved in a solvent by adjusting the solvent for dissolving the compound, infrared radiation emitted to the solution, and the concentration of the compound in the solution. Furthermore, the use of the infrared heater 10 of the MIM type allows a peak wavelength of emitted infrared radiation to be designed to accurately match a target wavelength. The first conductor layer 31 of the infrared heater 10 is configured as a metal pattern with a periodic structure in which the metal electrodes 32 of the same shape and size are arranged at regular intervals. The infrared heater 10 emits infrared radiation having a peak wavelength that changes with the lateral width W1 and the longitudinal width W2 of the metal electrodes 32. The lateral width W1 and the longitudinal width W2 of the metal electrodes 32 can be accurate as designed, for example, by drawing and lift-off using a well-known electron-beam lithography system. Thus, a peak wavelength of infrared radiation emitted from the infrared heater 10 can be relatively easily and accurately adjusted to a target wavelength.
It goes without saying that the present invention should not be limited to these embodiments and can be implemented in various aspects within the technical scope of the present invention.
The metal electrodes 32 are tetragonal in these embodiments but may be circular. In circular metal electrodes 32, the diameter corresponds to the lateral width W1 and the longitudinal width W2.
EXAMPLES Example 1Febuxostat is known to have a plurality of crystal forms F1, F2, Q, and H1.
A test sample was prepared by weighing 25 mg of febuxostat (product code F0847, Tokyo Chemical Industry Co., Ltd.) into a flat laboratory dish (ϕ32 mm × 16 mm), adding 1 mL of isopropanol (IPA), heating the febuxostat on a hot plate at 80° C. for 2 minutes, and dissolving the febuxostat with slight stirring (the concentration of febuxostat in the test sample was 25 [mg/mL] ) . The test sample was irradiated with infrared radiation including a wavelength of 6.7 µm (infrared radiation having a peak at a wavelength of 6.7 µm) (radiation source temperature: 400° C.) to evaporate the solvent and precipitate crystals. The temperature of the solution was 40° C. A heating plate was not used. Infrared radiation was emitted from the infrared heater 10 of the MIM type. In the infrared heater 10, the first conductor layer 31 (a layer having circular metal electrodes 32) made of Au had a height h of 50 nm. The dielectric layer 34 made of Al2O3 had a thickness d of 190 nm. The second conductor layer 35 made of Au had a height f of 100 nm. The circular metal electrodes 32 had a diameter (corresponding to W1 and W2) of 2.16 µm. The intervals between the metal electrodes (corresponding to D1 and D2) were 1.84 µm. The period (corresponding to Λ1 and Λ2) was 4.0 µm. Infrared radiation having a peak at a wavelength of 6.7 µm (half-width: 0.5 µm) was emitted. The crystal form of the precipitated crystals was identified as F2 by XRD analysis. The XRD analysis was performed with an X-ray diffractometer (product name: Ultima IV, Rigaku).
Example 2Crystals were precipitated in the same manner as in Example 1 except that the concentration of febuxostat in the test sample was changed from 25 mg/mL to 50 mg/mL. The crystal form of the precipitated crystals was identified as F1 by XRD analysis.
Example 3Loxoprofen is known to have a plurality of crystal forms F1 and F2.
A test sample was prepared by weighing 5 mg of loxoprofen (product code L0244, Tokyo Chemical Industry Co., Ltd.) into a flat laboratory dish (ϕ32 mm × 16 mm), adding 1 mL of isopropanol (IPA), heating the loxoprofen on a hot plate at 80° C. for 1 minute, and dissolving the loxoprofen with slight stirring (the concentration of loxoprofen in the test sample was 5 mg/mL). The temperature of the solution was adjusted to 80° C. while the test sample was irradiated with infrared radiation including a wavelength of 6.7 µm, and this state was maintained to evaporate the solvent and precipitate crystals. The temperature of the solution was adjusted by placing the test sample on a heating plate with a Peltier element and using the temperature control function of the heating plate. The crystal form of the precipitated crystals was identified as F1 by XRD analysis.
Example 4Crystals were precipitated in the same manner as in Example 3 except that the concentration of loxoprofen in the test sample was changed from 5 mg/mL to 100 mg/mL. The crystal form of the precipitated crystals was identified as F2 by XRD analysis.
Example 5Carbamazepine is known to have a plurality of crystal forms F1, F2, F3, and F4.
A test sample was prepared by weighing 25 mg of carbamazepine (product code C1095, Tokyo Chemical Industry Co., Ltd.) into a flat laboratory dish (ϕ32 mm × 16 mm), adding 1 mL of isopropanol (IPA), heating the carbamazepine on a hot plate at 80° C. for 1 minute, and dissolving the carbamazepine with slight stirring (the concentration of carbamazepine in the test sample was 25 mg/mL). The temperature of the solution was adjusted to 55° C. while the test sample was irradiated with infrared radiation including a wavelength of 3.0 µm, and this state was maintained to evaporate the solvent and precipitate crystals. A heating plate was not used. The crystal form of the precipitated crystals was identified as F2 by XRD analysis.
In Example 5, the first conductor layer 31 of the infrared heater 10 had a height h of 49 nm. The dielectric layer 34 had a thickness d of 44 nm. The second conductor layer 35 had a height f of 200 nm. The circular metal electrodes 32 had a diameter (corresponding to W1 and W2) of 0.54 µm. The intervals between the metal electrodes (corresponding to D1 and D2) were 0.46 µm. The period (corresponding to Λ1 and Λ2) was 1.0 µm. Infrared radiation having a peak at a wavelength of 3.0 µm (half-width: 0.5 µm) was emitted.
Example 6Crystals were precipitated in the same manner as in Example 5 except that the concentration of carbamazepine in the test sample was changed from 25 mg/mL to 120 mg/mL. The crystal form of the precipitated crystals was identified as F3 by XRD analysis.
The results of Examples 1 to 6 are summarized in Table 2.
Examples 1 to 6 show that the solvent, the wavelength, and the concentration of the compound in the solution could be appropriately combined to precipitate a compound with a different crystal form. From another perspective, even with the same solvent and wavelength, the compound concentration could be changed to precipitate a compound with a different crystal form.
Examples 1 and 2 show that, to precipitate febuxostat of the crystal form F1, as described in Example 1, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 25 mg/mL, and infrared radiation with a peak wavelength of 6.7 µm may be emitted. To precipitate febuxostat of the crystal form F2, as described in Example 2, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 50 mg/mL, and infrared radiation with a peak wavelength of 6.7 µm may be emitted.
Examples 3 and 4 show that, to precipitate loxoprofen of the crystal form F1, as described in Example 3, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 5 mg/mL, and infrared radiation with a peak wavelength of 6.7 µm may be emitted. To precipitate loxoprofen of the crystal form F2, as described in Example 4, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 100 mg/mL, and infrared radiation with a peak wavelength of 6.7 µm may be emitted.
Examples 5 and 6 show that, to precipitate carbamazepine of the crystal form F2, as described in Example 5, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 25 mg/mL, and infrared radiation with a peak wavelength of 3.0 µm may be emitted. To precipitate carbamazepine of the crystal form F3, as described in Example 6, IPA may be used as a solvent, a sample may be prepared at a compound concentration of 120 mg/mL, and infrared radiation with a peak wavelength of 3.0 µm may be emitted.
The present application claims priority to International Application No. PCT/JP2020/027266 filed on Jul. 13, 2020, the entire contents of which are incorporated herein by reference.
Claims
1. A refining method for crystallizing a compound with at least one crystal form, comprising:
- setting, as a target wavelength and a target concentration, a specific infrared wavelength and a specific concentration at which a specific crystal form precipitates from a solution of the compound dissolved in a solvent, and using an infrared radiation apparatus capable of emitting infrared radiation including the target wavelength to evaporate the solvent and precipitate the specific crystal form while irradiating a solution of the compound dissolved in the solvent at the target concentration with infrared radiation including the target wavelength.
2. The refining method according to claim 1,
- wherein the compound has a plurality of crystal forms.
3. The refining method according to claim 1,
- wherein the infrared radiation apparatus includes a sheet radiator and a planar heater serving as a heat source.
4. The refining method according to claim 1,
- wherein the infrared radiation apparatus can emit infrared radiation having a peak at the target wavelength.
5. The refining method according to claim 4,
- wherein the infrared radiation apparatus emits infrared radiation having a peak at the target wavelength from a structure composed of a metal pattern, a dielectric layer, and a metal substrate stacked in this order from the outside to the inside, the metal pattern includes metal electrodes of the same shape and size arranged at regular intervals on the dielectric layer, and a peak wavelength of the infrared radiation changes depending on a width of the metal electrodes.
6. The refining method according to claim 1,
- wherein the compound is febuxostat, loxoprofen, or carbamazepine.
Type: Application
Filed: Dec 28, 2022
Publication Date: Jun 1, 2023
Applicant: NGK Insulators, Ltd. (Nagoya-City)
Inventors: Norimitsu TOHNAI (Suita-City), Daiki KATO (Nagoya-City), Yoshio KONDO (Nagoya-City), Kazunari YAMADA (Nagoya-City)
Application Number: 18/147,198
