Magnetic particles used for medication management

Abstract

The present disclosure provides magnetic particles used for medication management. The present disclosure relates to a sensing magnetic probe that enables medication management. The magnetic probe according to the present disclosure exhibits a magnetic response rate of 5 to 10 times by producing, in a controlled manner, particles having a relatively small size but having an irregular shape or non-spherical shape. The present disclosure also provides a system for detecting medication by using the magnetic particles of the present disclosure. The system for detecting medication comprises: a formulation; a sensing means for sensing magnetism of the formulation; and a detection means for detecting that a subject has taken the formulation on the basis of the sensed magnetism.

Description

Magnetic particles for medication management

[0001] The present disclosure relates to magnetic particles for use in medication management, their manufacturing method, and their applications.

[0002] The efficacy of medicines depends on the patient's adherence to the medication. The use of magnetic probes can improve compliance. Reasons for leftover medication include self-administration, as-needed dosing, forgetting to take a dose, duplicate prescriptions, excessive prescription days, and adjustment of topical medications.

[0003] The present disclosure relates to a sensing magnetic probe that enables medication management. The magnetic probe of the present disclosure exhibits a magnetic response rate that is 5 to 10 times higher by controlling the production of particles with irregular or non-spherical shapes, even if they are relatively small. Use of a magnetic probe containing the magnetic particles of the present disclosure can prevent self-regulation and forgetting to take medication, which can cause leftover medication. The present disclosure is as follows: (Item 1) Magnetic particles having a non-spherical shape. (Item 1B) The magnetic particles according to the preceding items, wherein the non-spherical shape is determined by an image acquired with an electron microscope. (Item 1C) The magnetic particles according to any one of the preceding items, wherein the non-spherical shape is determined by an SEM (scanning electron microscope) or a TEM (transmission electron microscope). (Item 2) The magnetic particles are 0.5 x 10 －３The magnetic particles according to any one of the preceding items, characterized in that they have a magnetic response rate / particle size of μT / (mg-nm) or more. (Item 3) The magnetic particles according to any one of the preceding items, wherein the particle size of the magnetic particles is 10 nm to 500 nm. (Item 3B) The magnetic particles according to any one of the preceding items, wherein the particle size of the magnetic particles is measured from an image acquired by an electron microscope. (Item 3C) The magnetic particles according to any one of the preceding items, wherein the electron microscope is an SEM (scanning electron microscope) or a TEM (transmission electron microscope). (Item 4) The magnetic particles according to any one of the preceding items, wherein the magnetic particles are iron-containing metal magnetic particles or iron-containing metal oxide magnetic particles. (Item 5) The magnetic particles according to any one of the preceding items, characterized in that the magnetic particles have a sphericity of 1.1 or more. (Item 6) A magnetic particle agglomerate comprising magnetic particles having a non-spherical shape. (Item 7) A magnetic particle assembly according to any one of the preceding items, wherein the magnetic particles having a non-spherical shape are those described in any one of the preceding items. (Item 8) A magnetic particle assembly according to any one of the preceding items, wherein the content of the magnetic particles having a non-spherical shape is 40% or more relative to the total magnetic particles. (Item 9) A magnetic particle assembly according to any one of the preceding items, wherein the content of the magnetic particles having a non-spherical shape is 50% or more relative to the total magnetic particles. (Item 10) A composition comprising the magnetic particle assembly according to any one of the preceding items, wherein the content of the magnetic particles having a non-spherical shape is 50% or more relative to the total magnetic particles. (Item 11) A magnetic particle-containing ink containing the magnetic particles according to any one of the preceding items or the magnetic particle assembly according to any one of the preceding items. (Item 12) The magnetic particle-containing ink according to any one of the preceding items, wherein the ink is for printing the magnetic particles or the magnetic particle assembly on the surface of a formulation by inkjet printing. 13. The magnetic particle-containing ink of any one of the preceding claims, further comprising a dye or pigment. 14. The magnetic particle-containing ink of any one of the preceding claims, further comprising a solvent, a surfactant, an additive, or purified water.(Item 15) A method for producing the magnetic particles described in any one of the preceding items, or the magnetic particle assembly described in any one of the preceding items, comprising: a) forming nuclei by hydrolyzing a metal salt with water, b) forming a protective agent around the nuclei by adding a protective agent, and c) refluxing the nuclei having the protective agent. (Item 16) A method for producing the magnetic particles described in any one of the preceding items, or the magnetic particle assembly described in any one of the preceding items, comprising: a') hydrolyzing a sample containing a metal salt, b') adding a protective agent to the hydrolyzate of a'), c') refluxing the product obtained in b'), d') selecting and collecting desired magnetic particles or magnetic particle assembly as needed, and e') classifying particles of the desired particle size as needed. (Item 17) The method described in any one of the preceding items, wherein the concentration of the metal salt is 0.04 mol to 0.06 mol. (Item 18) The method of any one of the preceding items, wherein the metal salt comprises iron chloride, iron bromide, iron perchlorate, or iron hydroxide. (Item 19) The method of any one of the preceding items, wherein the hydrolysis is achieved by adding water. (Item 20) The method of any one of the preceding items, wherein the protecting agent comprises sodium acetate, sodium ascorbate, sodium malate, or sodium citrate. (Item 21) The method of any one of the preceding items, wherein the moiety of the protecting agent imparted to the nucleus is acetate ions, ascorbate ions, malate ions, or citrate ions. (Item 22) The method of any one of the preceding items, wherein step c') comprises a step of stirring at 90°C to 100°C before refluxing. (Item 23) Magnetic particles or magnetic particle aggregates produced by the method of any one of the preceding items. (Item 24) A formulation comprising the magnetic particles of any one of the preceding items or the magnetic particle aggregate of any one of the preceding items, an active ingredient, and, if necessary, an additive.(Item 25) The formulation according to any one of the preceding items, wherein the formulation is provided in the form of a tablet, capsule, caplet, pill, granule, or liquid. (Item 26) The formulation according to any one of the preceding items, wherein the magnetic particles or magnetic particle aggregates are contained in the formulation in a form printed by inkjet printing. (Item 26B) The formulation according to any one of the preceding items, wherein the magnetic particles or magnetic particle aggregates are printed on the medication so as to include information about the medication. (Item 26C) The formulation according to any one of the preceding items, wherein the information about the medication is conveyed by the number or dose of the magnetic particles. (Item 26D) The formulation according to any one of the preceding items, wherein the information about the medication includes visually recognizable information. (Item 27) A system for detecting medication ingestion, comprising: the formulation according to any one of the preceding items; sensing means for sensing the magnetism of the formulation; and detection means for detecting that a subject has taken the formulation based on the sensed magnetism. (Item 28) The system of any one of the preceding items, wherein the detection means detects the amount of the formulation taken by the subject based on the sensed magnetism. (Item 29) The system of any one of the preceding items, further comprising: a determination means for determining whether the subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation; and a means for taking an action in response to the result of the determination by the determination means. (Item 30) The system of any one of the preceding items, wherein the means for taking an action takes an action in response to determining that the subject has not taken the formulation at the predetermined time or that the subject has not taken the predetermined amount of the formulation, and the action includes at least one of issuing an alarm and sending a message. (Item 31) The system described in any one of the preceding items, wherein the means for performing an action performs an action in response to determining that the subject has taken the formulation at the predetermined time or that the subject has taken the predetermined amount of the formulation, and the action includes at least one of sending a message and storing medication information in association with a therapeutic effect.(Item 32) The dosage form has information printed on it using the magnetic particles, and the detection means detects the information based on the sensed magnetism. (Item 33) A method for detecting ingestion, wherein the dosage form to be taken contains the magnetic particles or the magnetic particle assembly of any one of the preceding items, or is the dosage form of any one of the preceding items, the method comprising: disposing sensing means for sensing the magnetism of the dosage form around a subject; sensing the magnetism of the dosage form from within the subject with the sensing means; and detecting that the subject has taken the dosage form based on the sensed magnetism. (Item 34) The method of any one of the preceding items, comprising: determining whether the subject has taken the dosage form at a predetermined time and / or whether the amount of the dosage form taken by the subject is a predetermined amount; and performing an action in response to determining that the subject has not taken the dosage form at the predetermined time or that the subject has not taken the predetermined amount of the dosage form. (Item 35) A program for detecting ingestion, the program being executed on a computer system including a processor, wherein a formulation to be administered contains the magnetic particles or the magnetic particle aggregate of any one of the preceding items, or is the formulation of any one of the preceding items, the program causing the processor to perform processing including: receiving a signal representing the magnetism of the formulation sensed by sensing means disposed around the subject, and detecting that the subject has taken the formulation based on the signal representing the magnetism. (Item 36) The program according to any one of the preceding items, wherein the processing includes: determining whether the subject has taken the formulation at a predetermined time and / or whether the amount of the formulation taken by the subject is a predetermined amount, and performing an action in response to the determination. (Item 37) The program according to any one of the preceding items, wherein the magnetic particles contained in the formulation are printed on the formulation, and information is imparted by the printing, and the information printed on the formulation is also used in the determination.It is contemplated that the present disclosure may provide one or more of the above-described features in combinations other than those explicitly stated. Still further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary.

[0004] By utilizing the results of this research, it has become possible to improve the magnetic response rate by 10 times by controlling the shape and content of magnetic particles of approximately 100 nm to 200 nm, which previously did not have a high magnetic response rate.

[0005] Figure 1 shows a schematic diagram of a cross section of a particle having an irregular shape. Figure 2 shows an example of a program for causing a processor unit to perform processing for detecting medication. Figure 3 shows an SEM image of the magnetic particles produced in Example 1. Figure 4 shows the relationship between the magnetic response rate and particle size of the magnetic particles produced in Example 1 and Comparative Example 1. Figure 5 shows the relationship between the magnetic response rate and sphericity of the magnetic particles produced in Example 1 and Comparative Example 1.

[0006] (Definitions) The present invention will be described in more detail below. Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. In addition, it should be understood that the terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention belongs. In the event of conflict, this specification (including definitions) will take precedence. First, the terms and general techniques used in this specification will be explained.

[0007] As used herein, the term "non-spherical shape" refers to a structure that does not have a true spherical shape. It is also referred to as "irregular shape" in this specification. Whether or not a particle has a non-spherical shape can be measured by observation using a microscope (for example, an electron microscope such as a scanning electron microscope (SEM) or a transmission electron microscope (TEM)), or by measuring the circularity, sphericity, or theoretical surface area ratio (R=Adα / 6, where R is the surface area ratio, d is the D50 particle diameter, α is the particle density, and A is the BET specific surface area).

[0008] As used herein, the term "magnetic particles" refers to ferromagnetic particles (such as Fe, Ni, and Co), ferrimagnetic particles (such as Fe, ２ O ３ , MnFe ２ O ４ , BAO6Fe ２ O ３ etc.), paramagnetic (Al, Ti, Cu alloy etc.), superparamagnetic (Fe ３ O ４ The term "magnetic particles" refers to particles having magnetism, such as particles having magnetic properties, and includes any particles having magnetism, regardless of the degree or type of magnetism. Examples of sizes include, but are not limited to, about 1 nm to about 1000 nm, about 1 nm to about 800 nm, about 1 nm to about 600 nm, about 1 nm to about 400 nm, about 10 nm to about 1000 nm, about 10 nm to about 800 nm, about 10 nm to about 600 nm, and about 10 nm to about 400 nm.

[0009] As used herein, "iron-containing metal magnetic particles" refers to magnetic particles that contain iron, which may be in the form of ions or salts.

[0010] As used herein, the term "iron-containing metal oxide magnetic particles" refers to iron oxide (e.g., Fe ２ O ３ and / or Fe ３ O ４ ) refers to magnetic particles containing

[0011] In this specification, the term "circularity" refers to the degree of circularity = (4πS / L ２) formula. Here, S is the two-dimensional projected area of ​​the particle, and L is the two-dimensional projected perimeter. To measure circularity, electron microscope images are binarized using image processing, and the circularity can be calculated for each particle. The two-dimensional projected area of ​​a particle is obtained by calculating the area of ​​the particle on the image from the acquired two-dimensional particle image. The two-dimensional projected perimeter is measured by measuring the acquired two-dimensional particle image, including notches such as edges. The circularity defined in this disclosure means the average circularity calculated by measuring 500 particles randomly. A circularity of 1.0 indicates a perfect sphere, and the lower the value, the more irregular the outer periphery and the greater the degree of irregularity. For magnetic particles having a non-spherical shape, the circularity is preferably 0.6 or less.

[0012] As used herein, "sphericity" is determined by observing particles in a micrograph and calculating the circumference and the sum of the lengths of the indentations on the particle surface according to the following formula: Sphericity = (Circumference + Total Length of Indentations on the Particle Surface) / Circumference. Here, an indentation is determined if (R1 - R2) / (R1) is 10% or greater, as shown in Figure 1. R1 is the radius of an imaginary sphere inscribed in a non-spherical particle, and R2 is the radius of an imaginary inner sphere whose center is the center of the imaginary sphere and whose periphery passes through the point closest to the center of the indentation. The length of the indentation is calculated by R1 - R2. When a particle has multiple indentations, the length of the indentations is calculated by summing the lengths of the indentations. The sphericity defined in this disclosure refers to the average value of the sphericity obtained by measuring 500 randomly selected particles. A sphericity of 1.0 indicates a perfect sphere, and the higher the value, the more irregular the periphery and the greater the degree of irregularity.

[0013] As used herein, "particle size" refers to the diameter of a particle, and the defined particle size range refers to the diameter range of each individual particle. In this specification, the particle size of magnetic particles is measured by images obtained using an electron microscope such as a SEM (scanning electron microscope) or a TEM (transmission electron microscope). Unless otherwise specified, the particle size is determined by an SEM (scanning electron microscope).

[0014] As used herein, the term "electron microscope" refers to a microscope that uses a beam of accelerated electrons as a light source for a sample to provide a magnified image. Examples include, but are not limited to, SEM (scanning electron microscope) and TEM (transmission electron microscope). These electron microscopes can be used to measure particle size, circularity, sphericity, etc.

[0015] In this specification, the term "magnetic particle aggregate" refers to an aggregate of multiple magnetic particles.

[0016] As used herein, the term "visibly discernible material" refers to a material that can be visually discerned and can be colored by adding it. Examples of the visually discernible material include, but are not limited to, dyes, pigments, etc.

[0017] As used herein, "ink" refers to a colored liquid or suspension for coloring a material. It also refers to a printing method in which printing is performed by spraying ink onto a material from a jetting architecture such as inkjet architecture.

[0018] As used herein, the term "core" refers to a basic substance used to form particles. For example, the core may be a metal or a metal oxide, and examples of the metal or metal oxide include iron, iron trioxide, or iron tetroxide, with iron trioxide being preferred. Since the present disclosure may be used in the pharmaceutical field, in this case the core is preferably a pharmaceutically acceptable substance, and is preferably a pharmaceutically acceptable metal or metal oxide.

[0019] As used herein, the term "metal salt" refers to a salt of a metal ion with a free acid. Metal ions can be generated by adding water and hydrolyzing the salt. Examples of metal salts include, but are not limited to, iron chloride, iron bromide, iron perchlorate, and iron hydroxide.

[0020] As used herein, the term "hydrolysis" refers to a chemical reaction in which water reacts with a compound to produce another compound, involving the cleavage of a chemical bond with the addition of hydrogen cations and hydroxide anions from the water. For example, when hydrolyzing an iron salt, the progress of the hydrolysis can be monitored using a titration reagent for iron(III) ions, such as EDTA.

[0021] As used herein, the term "protecting agent" refers to an agent for protecting nuclei. The use of a protecting agent can stop the size growth reaction of nuclei and stabilize them in a solvent. Examples of protecting agents include, but are not limited to, sodium acetate, sodium ascorbate, sodium malate, and sodium citrate.

[0022] As used herein, the term "protective substance" imparted by a "protective agent" refers to a reagent that, when added, can produce a protective substance for protecting the nucleus. Examples of protective substances include, but are not limited to, acetate ions, ascorbate ions, malate ions, and citrate ions.

[0023] As used herein, "administration" refers to dispensing an appropriate drug and giving it to a patient, and "taking a drug" refers to a patient taking a drug.

[0024] As used herein, "magnetic" includes any element that is magnetic, paramagnetic, and / or ferromagnetic.

[0025] As used herein, the term "sensing means for sensing magnetism" refers to a means capable of sensing magnetism and / or changes in a magnetic field. Examples of the sensing means include a magnetic sensor, and the sensing means may be in the form of a necklace, an adhesive sheet (which may be a patch, a tape, or the like), a strap, clothing, underwear, a brassiere, a belt, suspenders, or the like.

[0026] As used herein, "subject" refers to an animal, such as a mammal (including a human), that has been or will be the target of treatment, observation, or experiment. The methods described herein may be useful for human therapy and / or veterinary applications. In some embodiments, the subject is a mammal (or patient). In some embodiments, the subject (or patient) is a human, a domestic animal (e.g., a dog or cat), a livestock animal (e.g., a cow, a horse, a sheep, a goat, and a pig), and / or a laboratory animal (e.g., a mouse, a rat, a hamster, a guinea pig, a pig, a rabbit, a dog, and a monkey). In some embodiments, the subject (or patient) is a human.

[0027] (Preferred Embodiments) Preferred embodiments of the present disclosure will be described below. The embodiments provided below are provided for a better understanding of the present disclosure, and it is understood that the scope of the present disclosure should not be limited to the following description. Therefore, it is clear that those skilled in the art can make appropriate modifications within the scope of the present disclosure in light of the description herein. It is also understood that the following embodiments of the present disclosure can be used alone or in combination.

[0028] <Magnetic Particles> In one aspect, the present disclosure provides magnetic particles having a non-spherical shape. Using magnetic particles having a non-spherical shape can improve magnetic responsiveness, allowing magnetic sensors to detect the magnetic particles with high sensitivity. Whether magnetic particles have a non-spherical shape can be measured by observation using a microscope or the like, or by measuring the circularity, sphericity, or theoretical surface area ratio (R = Adα / 6, where R is the surface area ratio, d is the D50 particle diameter, α is the particle density, and A is the BET specific surface area).

[0029] In one embodiment, the particle size of the magnetic particles of the present disclosure is from about 1 nm to about 1000 nm, from about 1 nm to about 800 nm, from about 1 nm to about 600 nm, from about 1 nm to about 400 nm, from about 10 nm to about 1000 nm, from about 10 nm to about 800 nm, from about 10 nm to about 600 nm, or from about 10 nm to about 400 nm, preferably from 10 nm to 400 nm. Preferably, the particle size is such that it can be used in inkjet printing.

[0030] In one embodiment, the magnetic particles of the present disclosure are iron-containing metal magnetic particles or iron-containing metal oxide magnetic particles. The magnetic particles used in the present disclosure are preferably non-toxic to the human body.

[0031] In one embodiment, the circularity of the magnetic particles of the present disclosure is 0.9 or less, 0.8 or less, 0.7 or less, or 0.6 or less. Preferably, the circularity is 0.6 or less. By using magnetic particles having a non-spherical shape with a circularity of less than 1, magnetic response can be improved, and the magnetic particles can be detected with high sensitivity by a magnetic sensor.

[0032] In one embodiment, the sphericity of the magnetic particles of the present disclosure is preferably 1.01 or more, 1.02 or more, 1.03 or more, 1.04 or more, 1.05 or more, 1.06 or more, 1.07 or more, 1.08 or more, 1.09 or more, or 1.1 or more. More preferably, the sphericity is 1.1 or more. By using magnetic particles having a non-spherical shape with a sphericity of greater than 1, magnetic responsiveness can be improved, and the magnetic particles can be detected with high sensitivity using a magnetic sensor.

[0033] <Magnetic particle assembly> In one aspect, the present disclosure provides a magnetic particle assembly containing magnetic particles having a non-spherical shape used in the present disclosure. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in <Magnetic particles>.

[0034] In one embodiment, the content of the non-spherical magnetic particles of the present disclosure is 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 100% of the total magnetic particles. Preferably, the content of the non-spherical magnetic particles of the present disclosure is 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 100%. Preferably, it is 40% or more, or 50% or more.

[0035] Ink In one aspect, the ink of the present disclosure contains the magnetic particles or magnetic particle aggregates of the present disclosure and a visible material. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in the sections <Magnetic particles> and <Magnetic particle aggregates>.

[0036] In one embodiment, the ink of the present disclosure is used for printing the magnetic particles or magnetic particle aggregates of the present disclosure onto the surface of a formulation by inkjet printing. By printing on the surface of the formulation, formulation information, such as a two-dimensional barcode, can be written. Because the ink can be printed on the surface of the formulation, it can also be applied to existing formulations.

[0037] In one embodiment, the ink of the present disclosure may further include solvents, surfactants, additives, purified water, and the like.

[0038] In one embodiment, the ink of the present disclosure can be made visible by inkjet printing by including a visible material selected from the group consisting of dyes, pigments, solvents, surfactants, additives, purified water, and the like.

[0039] The solvent used in the present disclosure may include known solvents used in ink compositions. Examples of the solvent include alcohols such as ethanol, ethylene glycol, propylene glycol, and glycerin. In this case, the amount of the solvent added is preferably 0.5% by weight to 50% by weight, and more preferably 20% by weight to 45% by weight, of the composition. Among these, glycerin or propylene glycol is more preferred as the solvent. This is because these solvents are excellent humectants and are easily available.

[0040] The surfactant used in the present disclosure may include an edible surfactant. The surfactant adjusts the surface tension of the ink composition within an appropriate range, thereby improving the ejection stability of the ink. Examples of surfactants that can be used in the present invention include caffetannin, polyglycerin fatty acid esters, Quillaja saponin, propylene glycol fatty acid esters, lecithin, enzyme-treated lecithin, glycerin fatty acid esters, organic acid monoglycerides, amylose, barium chloride hydrate, sucrose fatty acid esters, sorbitan fatty acid esters, rosemary species, and sodium pyrophosphate. The surfactant may be used alone or in combination. The content of the surfactant in the composition is preferably 0.01% by weight to 0.5% by weight.

[0041] The additives used in the present disclosure are various additives typically used in ink compositions, and may include edible additives. Examples of such additives include chelating agents and antifungal agents. The amount of each of these additives is preferably 0.01% to 0.5% by weight in the composition. Among these, chelating agents are preferred because they are effective in improving the dispersibility of edible pigments. Examples of chelating agents include sodium hexametaphosphate and trisodium phosphate. Other additives include, but are not limited to, flavonoids, sodium carboxylate, calcium stearoyl lactylate lecithin, aerosil, potassium phosphate, sodium phosphate, polyvinyl, disodium hydrogen phosphate, potassium polyphosphate, tetrasodium pyrophosphate, sodium polyphosphate, guar gum, diacetyltartaric acid monoglyceride, pectin, tamarind gum, xanthan gum, potassium metaphosphate, carboxymethylcellulose, citric acid, hydroxypropyl cellulose, polyvinylpyrrolidone, sodium erythorbate, and methylcellulose. These additives may be used alone or in combination. The content of the additive in the composition is preferably 0.05 to 11% by weight.

[0042] The water used in the present disclosure is preferably highly pure water such as purified water, ion-exchanged water, etc. Considering the fluidity of the ink composition, the water content in the composition is preferably 20 wt % to 65 wt %, and more preferably 40 wt % to 60 wt %.

[0043] <Production Method> In one aspect, the present disclosure provides a method for producing the magnetic particles of the present disclosure or the magnetic particle assembly of the present disclosure. The method for producing the magnetic particles of the present disclosure or the magnetic particle assembly of the present disclosure includes the steps of: a) forming nuclei by hydrolyzing a metal salt with water; b) forming a protective substance around the nuclei by adding a protective agent; and c) refluxing the nuclei having the protective agent. It is understood that the various embodiments described herein can be applied in appropriate combination with any of the forms described in <Magnetic Particles>.

[0044] In one embodiment, the step of hydrolyzing a metal salt with water can be carried out by any method known in the art, and any method can be used as long as it can form nuclei.

[0045] In one embodiment, the protecting agent can be added by any method. The protecting agent can usually be added by adding a solution of the protecting agent dissolved in a suitable reaction solvent. Without wishing to be bound by theory, the addition of the protecting agent causes the protective substance component contained in the protecting agent to interact with the core, and a protective substance is formed around the core. The formation around the core can be via a covalent bond or a non-covalent bond (e.g., an ionic bond, a hydrophobic bond, etc.).

[0046] In one embodiment, refluxing the core with the protecting agent can typically be accomplished by heating a suitable reaction solvent to the reflux temperature.

[0047] In one aspect, the present disclosure provides a method for producing the magnetic particles or magnetic particle aggregates of the present disclosure. The method for producing the magnetic particles or magnetic particle aggregates of the present disclosure includes the steps of: a') hydrolyzing a sample containing a metal salt; b') adding a protective agent to the hydrolyzate of a'); c') refluxing the product obtained in b'); d') optionally selecting and collecting desired magnetic particles or magnetic particle aggregates; and e') optionally classifying particles of a desired particle size. It will be understood that the various embodiments described herein can be applied in appropriate combination with any of the embodiments described under <Magnetic Particles>.

[0048] In one embodiment of this aspect, the step of hydrolyzing the metal salt with water can be carried out by any method known in the art, and is preferably carried out under conditions that result in nucleation, which is typically achieved by mixing the metal salt with a suitable reaction solvent.

[0049] In one embodiment, the addition of the protecting agent can be carried out by any method. Without wishing to be bound by theory, the addition of the protecting agent is preferably carried out under conditions in which a protecting substance is formed around the core. The conditions in which a protecting substance is formed can usually be carried out by mixing the protecting agent together with the core in a suitable reaction solvent.

[0050] In one embodiment, refluxing of the cores with the protecting agent can typically be carried out by heating a suitable reaction solvent to the reflux temperature, preferably under conditions that result in the formation of the desired magnetic particles or magnetic particle aggregates.

[0051] In one embodiment, the concentration of the metal salt of the present disclosure used in step a) or step a′) is high, for example, 0.02 mol to 0.1 mol, 0.02 mol to 0.09 mol, 0.02 mol to 0.08 mol, 0.02 mol to 0.07 mol, 0.02 mol to 0.06 mol, 0.02 mol to 0.05 mol, 0.02 mol l~0.04mol, 0.02mol~0.03mol, 0.03mol~0.1mol, 0.03mol~0.09mol, 0.03mol~0.08mol, 0.03m ol~0.07mol, 0.03mol~0.06mol, 0.03mol~0.05mol, 0.03mol~0.04mol, 0.04mol~0.1mol, 0.04m ol ~ 0.09 mol, 0.04 mol ~ 0.08 mol, 0.04 mol ~ 0.07 mol, 0.04 mol ~ 0.06 mol, 0.04 mol ~ 0.05 mol, 0.0 5 mol to 0.1 mol, 0.05 mol to 0.09 mol, 0.05 mol to 0.08 mol, 0.05 mol to 0.07 mol, 0.05 mol to 0.06 mol, 0. The metal salt concentration is preferably 0.06 mol to 0.1 mol, 0.06 mol to 0.09 mol, 0.06 mol to 0.08 mol, 0.06 mol to 0.07 mol, 0.07 mol to 0.1 mol, 0.07 mol to 0.09 mol, 0.07 mol to 0.08 mol, 0.08 mol to 0.1 mol, 0.08 mol to 0.09 mol, or 0.09 mol to 0.1 mol. Preferably, the metal salt concentration is 0.04 mol to 0.06 mol. Use of a high concentration can increase the probability of collisions between metal salt particles, thereby improving the probability of forming magnetic particles having a non-spherical shape.

[0052] In one embodiment, the metal salt of the present disclosure may be any salt that forms metal ions upon hydrolysis, and is preferably an iron salt, more preferably iron chloride, iron bromide, iron perchlorate, or iron hydroxide.

[0053] In one embodiment, the hydrolysis in step a) or a') is achieved by adding water. The concentration of water used for hydrolysis in step a) or a') is high, for example, 0.1 mol to 1 mol, 0.1 mol to 0.9 mol, 0.1 mol to 0.8 mol, 0.1 mol to 0.7 mol, 0.1 mol to 0.6 mol, 0.1 mol to 0.5 mol, 0.1 mol to 0.4 mol, 0.1 mol to 0.03 mol, 0.1 mol to 0. .. 02 mol, 0.2 mol to 1 mol, 0.2 mol to 0.9 mol, 0.2 mol to 0.8 mol, 0.2 mol to 0.7 mol, 0.2 mol to 0.6 mol, 0.2 mol to 0 .5mol, 0.2mol~0.4mol, 0.2mol~0.3mol, 0.3mol~1mol, 0.3mol~0.9mol, 0.3mol~0.8mol, 0.3mol~0. 7 mol, 0.3 mol to 0.6 mol, 0.3 mol to 0.5 mol, 0.3 mol to 0.4 mol, 0.4 mol to 1 mol, 0.4 mol to 0.9 mol, 0.4 mol to 0.8 mol, 0.4 mol to 0.7 mol, 0.4 mol to 0.6 mol, 0.4 mol to 0.5 mol, 0.5 mol to 1 mol, 0.5 mol to 0.9 mol, 0.5 mol to 0.8 m mol, 0.5 mol to 0.7 mol, 0.5 mol to 0.6 mol, 0.6 mol to 1 mol, 0.6 mol to 0.9 mol, 0.6 mol to 0.8 mol, 0.6 mol to 0.7 mol, 0.7 mol to 1 mol, 0.7 mol to 0.9 mol, 0.7 mol to 0.8 mol, 0.8 mol to 1 mol, 0.8 mol to 0.9 mol, 0.9 mol to 1 mol. Preferably, the concentration of water is 0.4 mol to 0.6 mol. Using a high concentration of water can increase the probability of collisions between metal ions generated by hydrolysis, thereby improving the probability of forming magnetic particles having a non-spherical shape.

[0054] In one embodiment, the hydrolysis in step a) or a') is achieved by heating. The temperature used for the hydrolysis in step a) or a') is, for example, 50°C to 100°C, 50°C to 90°C, 50°C to 80°C, 50°C to 70°C, 50°C to 60°C, 60°C to 100°C, 60°C to 90°C, 60°C to 80°C, 60°C to 70°C, 70°C to 100°C, 70°C to 90°C, 70°C to 80°C, 80°C to 100°C, 80°C to 90°C, or 90°C to 100°C. Preferably, the hydrolysis is achieved at 70°C to 80°C. Heating activates the movement of the substance and increases collision energy, thereby increasing the probability of metal ion collisions and improving the probability of forming magnetic particles having a non-spherical shape.

[0055] In one embodiment, the protective agent of the present disclosure is sodium acetate, sodium ascorbate, sodium malate, or sodium citrate. The protective agent can control the size growth reaction of the nuclei during nucleation and stabilize them in the solvent. Furthermore, the particles can be made monodisperse, allowing the production of small particles.

[0056] In one embodiment, step b) or b') of the present disclosure includes a step of heating and stirring after adding the protective agent. The heating temperature here is, for example, 50°C to 100°C, 50°C to 90°C, 50°C to 80°C, 50°C to 70°C, 50°C to 60°C, 60°C to 100°C, 60°C to 90°C, 60°C to 80°C, 60°C to 70°C, 70°C to 100°C, 70°C to 90°C, 70°C to 80°C, 80°C to 100°C, 80°C to 90°C, or 90°C to 100°C. Preferably, the temperature is 90°C to 100°C. Heating can promote the reduction reaction of metal ions to metal and further the bond formation between the protective agent and iron.

[0057] In one embodiment, in step b) or step b'), the binding of the protective agent to the magnetic particles or their cores can be confirmed by electrophoresis or zeta potential measurement. Also, a change in the binding state of the protective agent can be confirmed by using X-ray photoelectron spectroscopy (XPS) or infrared absorption spectroscopy (IR).

[0058] In one embodiment, step c') of the present disclosure includes a step of heating and stirring before refluxing. The heating temperature here is, for example, 50°C to 100°C, 50°C to 90°C, 50°C to 80°C, 50°C to 70°C, 50°C to 60°C, 60°C to 100°C, 60°C to 90°C, 60°C to 80°C, 60°C to 70°C, 70°C to 100°C, 70°C to 90°C, 70°C to 80°C, 80°C to 100°C, 80°C to 90°C, or 90°C to 100°C. Preferably, this is achieved at 90°C to 100°C. By activating the movement of substances and increasing collision energy, the probability of metal ions colliding can be increased, thereby improving the probability of forming magnetic particles having a non-spherical shape.

[0059] In one embodiment, step d') of the present disclosure comprises collecting the magnetic particles and sorting the desired magnetic particles or collections of magnetic particles, so that only the more magnetic nanoparticles are isolated.

[0060] <Preparation> In one aspect, the present disclosure provides a preparation comprising the magnetic particles or magnetic particle aggregates of the present disclosure, an active ingredient, and, if necessary, additives. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in <Magnetic particles>, <Magnetic particle aggregates>, and <Ink>. In this disclosure, the term "active ingredient" is used in the same sense as commonly used in the art, and refers to any ingredient that is effective in treating or preventing the disease, disorder, or symptom that is the target of treatment or prevention.

[0061] In one embodiment, the magnetic particles or magnetic particle aggregates of the present disclosure are included in the formulation in inkjet printed form.

[0062] In one embodiment, the formulations of the present disclosure are provided in the form of tablets, capsules, caplets, pills, or granules, as well as liquids.

[0063] In one embodiment, the magnetic particles or magnetic particle collections of the present disclosure can be printed onto a pharmaceutical formulation to include information about the formulation.

[0064] In one embodiment, the information on the formulation of the present disclosure may be the type of formulation (e.g., active ingredient and, if necessary, additives), dosage, and / or usage, etc., and is conveyed by printing ink containing the magnetic particles or magnetic particle aggregates of the present disclosure on the formulation.

[0065] In one embodiment, information about the formulation of the present disclosure, such as the number and dosage, is transmitted by detecting magnetic information from the magnetic particles. By detecting magnetic information, it is possible to prevent forgetting to take a dose, taking too much medicine, taking the wrong medicine, checking combinations of medicines (contraindications), checking expiration dates (lot numbers), reducing the burden on caregivers, and improving the efficiency of remaining medicine management.

[0066] The particles of the present disclosure can be printed onto a formulation using an appropriate dosage form and administered orally. Specific examples of these dosage forms include, but are not limited to, tablets, capsules, caplets, etc. These formulations can be produced by known methods, such as by adding additives commonly used as pharmaceutical additives to the active ingredient.

[0067] These additives may include, depending on the purpose, excipients, disintegrants, binders, fluidizing agents, lubricants, coating agents, solubilizers, solubilizers, thickeners, dispersants, stabilizers, sweeteners, flavors, etc. Specific examples of these additives include, but are not limited to, lactose, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, corn starch, partially pregelatinized starch, carmellose calcium, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, propylene glycol, titanium oxide, talc, etc.

[0068] In one embodiment, the information on the formulations of the present disclosure comprises visually perceptible information.

[0069] (Synthesis Examples) (Method for Producing Magnetic Particles of the Present Disclosure) Specific synthesis examples of the method for producing magnetic particles of the present disclosure are given below in the Examples, but the present disclosure is not limited to these. Representative schemes are given below for explanation, but the present disclosure is not limited to these.

[0070] The magnetic particles of the present disclosure can be produced by, for example, but not limited to, the production methods described below. These production methods can be modified as appropriate based on the knowledge of those skilled in the art. A metal salt of iron is dissolved in a solvent such as ethylene glycol, and the solution is heated and stirred. Next, pure water is added, and the solution is heated and stirred. Next, a protective agent such as sodium acetate is added, and the solution is heated and stirred. Finally, the mixture is refluxed to produce magnetic particles.

[0071] (Applications) The magnetic particles, magnetic particle aggregates, inks, and formulations or medication systems printed with magnetic particles of the present disclosure can be used for any application, such as in tablet ink development, detection devices, and medication management systems. The method of the present disclosure provides magnetic particles, magnetic particle aggregates, inks, and formulations or medication systems printed with magnetic particles for these applications. Preferably, magnetic nanoparticles can be printed on the surface of tablets by high-speed inkjet printing, enabling sensing using a smart necklace or the like, and tablet type identification using a sensor. Alternatively, services can be provided to patients, their families, and medical professionals, providing individual support through combined analysis of vital signs and notifying them of the effectiveness of medication.

[0072] Without wishing to be bound by theory, the formulation or medication system of the present disclosure may offer unprecedented benefits in terms of safety, cost, and versatility. For example, safety in the body is guaranteed, and it is dramatically safer than embedding a chip in a tablet. In terms of cost, mass production is possible easily and inexpensively, so there is no increase in cost due to the difficulty of production. In terms of versatility, it does not require major changes to the formulation, the regulatory hurdles are low, and under Japanese regulations it is deemed possible to make changes with just a minor change notification, and it can be applied to existing drugs, which may be advantageous in some respects compared to technologies that have high cost and regulatory hurdles and are difficult to apply to various drugs.

[0073] (Example of Medication System) A system for detecting medication of the present disclosure (sometimes referred to herein as a medication system) can determine the type of tablet taken by the subject, whether the subject took the tablet at a predetermined time, and / or whether the subject took a predetermined amount by attaching a detection device (e.g., a necklace-type detection device or a patch-type detection device) capable of detecting the magnetic particle assembly of the present disclosure to a subject by wearing or attaching it to a part of the subject's digestive tract where the digestive tract can be detected (e.g., the subject's neck or chest). The information disclosed herein can be combined with vital data, activity data, dietary data, sleep data, etc. for each subject to provide data on the effects of medication, etc., tailored to each subject's lifestyle.

[0074] <Medication System> In one aspect, the present disclosure provides a system for detecting medication ingestion. Here, the system for detecting medication ingestion comprises a formulation of the present disclosure, a sensing means for sensing the magnetism of the formulation, and a detection means for detecting that a subject has taken the formulation based on the sensed magnetism. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in <magnetic particles>, <magnetic particle aggregates>, and <ink>. Unless otherwise specified, the term "formulation" described below refers to the "formulation" of the present disclosure.

[0075] The detection means of the present disclosure can detect that a subject has taken a formulation based on, for example, the intensity of the sensed magnetic field, the distribution (location) of the sensed magnetic field, the type of the sensed magnetic field, and the printing method. For example, when the intensity of the sensed magnetic field exceeds a predetermined threshold, it can detect that a subject has taken a formulation. The predetermined threshold may be a fixed value or a variable value. For example, the predetermined threshold may be set according to the subject's attributes (e.g., gender, age, presence or absence of a disease, etc.).

[0076] In one embodiment, the detection means of the present disclosure detects the amount of formulation taken by the subject based on the sensed magnetic field. For example, the detection means may detect the amount of formulation taken by the subject using a function that defines the relationship between the sensed magnetic field intensity and the amount of formulation taken, or may detect the amount of formulation taken by the subject using a lookup table that defines the relationship between the sensed magnetic field intensity and the amount of formulation taken, or may detect the amount of formulation taken by the subject using machine learning. When machine learning is used to detect the amount of formulation, the machine learning model used learns the relationship between magnetic field intensity and the amount of formulation taken. For example, data from multiple trials is trained using magnetic field intensity as input training data and the amount of formulation taken at that time as output training data. In this case, the multiple trials may be for a single subject or for multiple subjects.

[0077] In one embodiment, the system of the present disclosure further comprises a determination means for determining whether the subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation, and a means for taking an action in response to the result of the determination by the determination means.

[0078] The determining means can communicate with the detecting means and can receive information from the detecting means regarding the subject's administration of the formulation. The information regarding the subject's administration of the formulation can include at least one of the fact that the subject has administered the formulation, the amount of the formulation administered by the subject, and information printed on the formulation administered by the subject.

[0079] The determination means, for example, identifies the time when the subject took the formulation based on information received from the detection means. Then, by determining whether the identified time is a predetermined time, it is possible to determine whether the subject took the formulation at the predetermined time. For example, if the subject is instructed to take the formulation after waking up, the determination means determines whether the identified time is between 6:00 and 8:00 AM. The predetermined time may be, for example, a time window with such a range, or a pinpoint time.

[0080] The determination means, for example, identifies the amount of the formulation taken by the subject based on information received from the detection means. Then, by determining whether the identified amount is a predetermined amount, it is possible to determine whether the subject has taken the predetermined amount of the formulation. For example, if the subject is instructed to take one tablet of the formulation per dose, the determination means determines whether the identified amount of the formulation is one tablet.

[0081] The determination means can use information received from the detection means in combination with other sensors (such as sensors that can determine chewing and swallowing status, blood glucose level, body temperature, pulse rate, blood oxygen concentration, and whether the patient is lying down). Examples of information that can be obtained from other sensors and can be utilized by acquiring it simultaneously or in parallel with medication include, but are not limited to, the following: breathing, voice, eye movement, excretion, and facial expression; location information; number of steps, walking speed, activity level, diet, and calorie intake; vital signs (heart rate, blood pressure, blood glucose level, blood flow, blood oxygen saturation, sleep data, brain waves, weight, body temperature, and basal body temperature); electronic medical record data, and health checkup and medical examination data. Combining medication data with the above information can be used to visualize treatment effects and motivate patients, and to visualize treatment effects from medical professionals and caregivers, as well as for disease management, recurrence prevention, and prognosis management.

[0082] In one embodiment, the means for performing an action of the present disclosure can perform an action in response to determining that the subject has not taken the formulation at a predetermined time or that the subject has not taken the formulation in the predetermined amount. This occurs when the subject has not taken the formulation as instructed, i.e., when there is poor compliance. Therefore, the action at this time can be to encourage the subject to take the formulation. For example, the action can be to issue an alarm, and the means for performing the action can be a notification means. The alarm can be issued visually (e.g., by a light), audibly (e.g., by an alarm sound), tactilely (e.g., by a vibration), or olfactoryly (e.g., by a smell). For example, the action can be to send a message, and the means for performing the action can be a communication means. The message can be, for example, a message encouraging the subject to take the formulation, and can be sent to the subject's information terminal. The message may be, for example, a message informing the subject that the subject has not taken their medication, and may be sent to people around the subject (for example, the subject's family, doctor, nurse, caregiver, etc.) Here, the information terminal may be, for example, but is not limited to, a mobile phone, a smartphone, a tablet, a smart watch, smart glasses, a personal computer, a smart speaker, or a smart TV.

[0083] In one embodiment, the means for performing an action of the present disclosure can perform an action in response to determining that the subject has taken the formulation at a predetermined time or that the subject has taken a predetermined amount of the formulation. This occurs when the subject is taking the formulation as instructed, i.e., when medication compliance is good. Therefore, the action at this time can be to maintain motivation to take the medication. For example, the action can be sending a message, and in this case, the means for performing the action can be a communication means. The message can be, for example, a message praising the subject for taking the medication and can be sent to the subject's information terminal. The message can be, for example, a message informing the subject that the medication has been taken and can be sent to people around the subject (e.g., the subject's family, doctor, nurse, caregiver, etc.). For example, the action can be to associate and store medication information with a therapeutic effect, and in this case, the means for performing the action can be a storage means. For example, a record of medication is stored in a medication diary or the like.

[0084] In one embodiment, the formulation of the present disclosure has information printed thereon using magnetic particles, and the detection means detects the information based on the sensed magnetism. More specifically, the formulation has information on the type, dosage, and / or usage of the drug printed thereon using magnetic particles, and the detection means receives a signal from a magnetic sensor to detect the strength, distribution (position), and type of the magnetic field.

[0085] The above-described system for detecting medication can be implemented by a system including, for example, a magnetic sensor and an information processing device.

[0086] The sensing means for sensing the magnetism of the above-mentioned formulation can be implemented by a magnetic sensor. The magnetic sensor is configured to be able to communicate with an information processing device. The magnetic sensor and the information processing device can communicate in any manner. For example, the magnetic sensor and the information processing device may communicate by wire or wirelessly.

[0087] The information processing device may be any device capable of processing information, and may typically be a mobile phone, smartphone, tablet, smart watch, or personal computer, and preferably may be a portable device.

[0088] The information processing device includes an interface unit, a processor, and a memory.

[0089] The interface unit exchanges information with the outside of the information processing device. The processor of the information processing device can receive information from the outside of the information processing device and can transmit information to the outside of the information processing device via the interface unit. The interface unit can exchange information in any format. For example, a magnetic sensor can transmit a signal to the information processing device via the interface unit. For example, a terminal device of a target or a person around the target can communicate with the information processing device via the interface unit.

[0090] The interface unit includes, for example, an input unit that allows information to be input to the information processing device. It does not matter how the input unit allows information to be input to the information processing device. For example, if the input unit is a receiver, the receiver may input information from outside the information processing device via a network. For example, if the input unit is a data reading device, the input unit may input information by reading information from a storage medium connected to the information processing device. The information input to the interface unit is passed to the processor, which receives it.

[0091] The interface unit includes, for example, an output unit that enables information to be output from the information processing device. It does not matter in what manner the output unit enables information to be output from the information processing device. For example, if the output unit is a display, the information may be output by displaying a screen on the display. For example, if the output unit is a speaker, the information may be output by sound to the outside. For example, if the output unit is a data writing device, the information may be output by writing the information to a storage medium connected to the information processing device. Alternatively, if the output unit is a transmitter, the transmitter may output the information by transmitting it to an outside of the information processing device via a network.

[0092] The processor executes the processing of the information processing device and controls the operation of the entire information processing device. The processor reads a program stored in memory and executes the program. This allows the information processing device to function as a system that executes desired steps. The processor may be implemented by a single processor or by multiple processors.

[0093] The memory stores programs required to execute the processing of the information processing device, data required to execute the programs, etc. The memory may store a program for causing the processor unit to execute processing for detecting medication ingestion (for example, a program that realizes the processing shown in FIG. 2). Here, how the program is stored in the memory does not matter. For example, the program may be pre-installed in the memory. Alternatively, the program may be installed in the memory by being downloaded via a network. Alternatively, the program may be stored in a non-transitory computer-readable storage medium. The memory may be implemented by any storage means.

[0094] For example, the above-described detecting means and determining means can be implemented by a processor of the information processing device. For example, the above-described action taking means can be implemented by the processor of the information processing device, or by a processor and an interface unit. Alternatively, the action taking means can be implemented by an external device that communicates with the information processing device.

[0095] For example, the processor of the information processing device described above can perform the processing shown in FIG. 2. First, a signal representing the magnetism of the formulation sensed by the sensing means is received. Next, it is detected that the subject has taken the formulation based on the signal representing the magnetism. Next, it is confirmed whether the subject has taken the formulation as instructed. If the subject has taken the formulation as instructed, an instruction is issued to take an action to maintain the subject's motivation to take the formulation as instructed. If the subject has not taken the formulation as instructed, an instruction is issued to take an action to encourage the subject to take the formulation as instructed.

[0096] In one embodiment, there is provided a method for detecting ingestion of a medication of the present disclosure, wherein the medication to be administered comprises magnetic particles or magnetic particle aggregates of the present disclosure, or is a medication of the present disclosure, and the method includes placing a sensing means for sensing the magnetism of the medication around the subject, sensing the magnetism of the medication from within the subject by the sensing means, and detecting that the subject has taken the medication of the medication based on the sensed magnetism.

[0097] In one embodiment, the present disclosure includes determining whether a subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation, and performing an action in response to determining that the subject has not taken the formulation at the predetermined time or that the subject has not taken the predetermined amount of the formulation.

[0098] In one embodiment, there is provided a program for detecting ingestion of the present disclosure. The program is executed on a computer system including a processor, and the administered formulation includes the magnetic particles or magnetic particle aggregates of the present disclosure, or is the formulation of the present disclosure. The program of the present disclosure can also cause the processor to perform processes including receiving a signal representing the magnetism of the formulation sensed by a sensing means disposed around the subject, and detecting that the subject has ingested the formulation based on the signal representing the magnetism.

[0099] In one embodiment, the process of the present disclosure includes determining whether a subject has taken a formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation, and taking an action in response to the determination.

[0100] In one embodiment, the magnetic particles contained in the formulation of the present disclosure are printed on the formulation, and information is imparted to the magnetic particles by printing, and the information printed on the formulation is also used in the determination.

[0101] In one embodiment, the information disclosed herein can be combined with vital data, activity data, dietary data, sleep data, etc., for each subject to provide data tailored to each subject's lifestyle, such as the effects of medication.

[0102] The following examples illustrate the implementation of the present disclosure, but the present disclosure is not limited to these. While the reagents used were specifically products described in the examples, equivalent products from other manufacturers (Sigma-Aldrich, Wako Pure Chemical Industries, Nakarai, etc.) can also be used.

[0103] (Example 1: Preparation of magnetic particles) The details are as follows. (Procedure) FeCl ３ ・6H ２ 0 was dissolved in ethylene glycol. ３ ・6H ２The O-ethylene glycol solution was kept at 70°C and stirred for 80 minutes. 0.44 mol of pure water was added, and the mixture was further heated and stirred at 70°C for 60 to 120 minutes. Sodium acetate was then added, and the mixture was stirred at 100°C for 1 hour, and then refluxed for 50 to 80 hours. The production of magnetic particles was determined by confirming that the color of the solution had changed from brown to black. The obtained magnetic particles were classified by particle size using a method known in the art.

[0104] Comparative Example 1: Confirmation of Sizing Effect As a raw material, iron trichloride hexahydrate (FeCl ) was used in the molar amounts shown in Table 1 below. ３ ・6H ２ O), sodium acetate (CH ３ COONa), distilled water (H ２ 0) was dissolved in ethylene glycol. After stirring at room temperature for 20 hours, magnetic particles with a sphericity of 1 were produced by refluxing (197°C) for 2 days. The size was controlled by changing the ratio of the raw materials introduced (molar amount: mol; the values ​​in the table for iron trichloride, sodium acetate, and distilled water refer to mol amounts), and the results are summarized in Table 1.

[0105]

[0106] (Example 2: Evaluation of magnetic particles) Electron microscope images of the magnetic particles produced in Example 1 were obtained using an SEM ( Figure 3 ). Five hundred particles were analyzed from the obtained electron microscope images to measure particle size and sphericity. Next, the magnetic properties of the magnetic particles obtained in Example 1 and Comparative Example 1 were measured. The magnetic properties were measured using a magnetic sensor. The magnetic response rate (slope of the calibration curve) (mT / g) was obtained by dividing the obtained magnetic property by the mass of the measured magnetic particles. The magnetic response rates and particle sizes of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in Figure 4 . The magnetic response rates and sphericity of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in Figure 5 . The magnetic response rates and sphericity of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in Table 2.

[0107]

[0108] (Example 3: Preparation of magnetic particle-containing ink) A magnetic particle-containing ink of the present disclosure is prepared using a method similar to that described in JP 2016-37566 A. The magnetic particles, solvent, surfactant, and additives prepared in Example 1 are placed in a beaker and stirred together with zirconia beads using a magnetic stirrer at room temperature for 4 hours to obtain an ink composition.

[0109] Example 4: Preparation of magnetic particle-containing formulation The ink composition obtained in the above example is used to print on a tablet with an inkjet printer to prepare a magnetic particle-containing formulation.

[0110] Example 5: Animal experiment: A magnetic particle-containing formulation of the present disclosure is orally administered to a dog or monkey equipped with a magnetic sensor. Then, a comparison is made between the magnetic particle-containing formulation and a placebo, and the administration of the magnetic particle-containing formulation of the present disclosure after passing through the body of the dog or monkey can be evaluated.

[0111] (Example 6: Application to humans: Dosage example) A magnetic particle-containing formulation of the present disclosure is administered to a person wearing a magnetic sensor. Data from the magnetic sensor is analyzed to analyze the type of formulation taken, the amount of formulation taken, and the timing of administration. If the type of formulation taken, the amount of formulation taken, and the timing of administration can be measured, this can be widely used in medication management systems. Therefore, it is possible to measure which formulation was taken, when, and in what amount for multiple types of formulation, and by combining this with vital data, activity data, dietary data, sleep data, etc., it is possible to analyze the effects of medication tailored to a person's lifestyle.

[0112] (Note) As described above, the present disclosure has been illustrated using preferred embodiments thereof, but it is understood that the scope of the present disclosure should be interpreted solely by the scope of the claims. It is understood that the patents, patent applications, and other documents cited in this specification are incorporated by reference into this specification in their entirety as if the contents themselves were specifically set forth herein. This application claims priority to Japanese Patent Application No. 2023-121116, filed with the Japan Patent Office on July 25, 2023, the contents of which are incorporated by reference in their entirety.

[0113] The technology provided in the present disclosure can be used in any field that utilizes technology for observing magnetism within the body.

Claims

1. Magnetic particles with non-spherical shape.

2. The magnetic particles are 0.5×10 －３ 2. The magnetic particle according to claim 1, characterized in that it has a magnetic response rate / particle size of μT / (mg·nm) or more.

3. The magnetic particles according to claim 1 or 2, wherein the particle size of the magnetic particles is 10 nm to 500 nm.

4. The magnetic particles according to any one of claims 1 to 3, wherein the magnetic particles are iron-containing metal magnetic particles or iron-containing metal oxide magnetic particles.

5. The magnetic particles according to any one of claims 1 to 4, characterized in that the magnetic particles have a sphericity of 1.1 or more.

6. A magnetic particle assemblage comprising magnetic particles having a non-spherical shape.

7. The magnetic particle assembly according to claim 6, wherein the non-spherical magnetic particles are those according to any one of claims 2 to 5.

8. The magnetic particle assembly according to claim 6 or 7, wherein the content of said magnetic particles having a non-spherical shape is 40% or more with respect to the total amount of magnetic particles.

9. The magnetic particle assembly according to any one of claims 6 to 8, wherein the content of said magnetic particles having a non-spherical shape is 50% or more relative to the total amount of magnetic particles.

10. A composition comprising the magnetic particle assembly according to any one of claims 6 to 9, wherein the content of said magnetic particles having a non-spherical shape is 50% or more relative to the composition.

11. A magnetic particle-containing ink comprising the magnetic particles according to any one of claims 1 to 5 or the magnetic particle aggregate according to any one of claims 6 to 10.

12. The magnetic particle-containing ink according to claim 11, wherein the ink is for printing the magnetic particles or the magnetic particle aggregates on the surface of a formulation by inkjet.

13. The magnetic particle-containing ink according to claim 11 or 12, further comprising a dye or pigment.

14. The magnetic particle-containing ink according to any one of claims 11 to 13, further comprising a solvent, a surfactant, an additive or purified water.

15. A method for producing a magnetic particle according to any one of claims 1 to 5, or a magnetic particle assembly according to any one of claims 6 to 9, comprising the steps of: a) forming a nucleus by hydrolyzing a metal salt with water; b) adding a protective agent to form a protective agent around the nucleus; and c) refluxing the nucleus having the protective agent.

16. A method for producing the magnetic particles according to any one of claims 1 to 5, or the magnetic particle aggregate according to any one of claims 6 to 9, comprising the steps of: a') hydrolyzing a sample containing a metal salt; b') adding a protective agent to the hydrolyzate of a'); c') refluxing the product obtained in b'); d') selecting and collecting desired magnetic particles or magnetic particle aggregates as required; and e') classifying particles of a desired particle size as required.

17. The method according to claim 15 or 16, wherein the concentration of the metal salt is from 0.04 mol to 0.06 mol.

18. The method of any one of claims 15 to 17, wherein the metal salt comprises iron chloride, iron bromide, iron perchlorate or iron hydroxide.

19. The method of claim 15 or 16, wherein the hydrolysis is accomplished by adding water.

20. The method of claim 15 or 16, wherein the protecting agent comprises sodium acetate, sodium ascorbate, sodium malate or sodium citrate.

21. The method of claim 15 or 16, wherein the moiety applied to the nucleus by the protecting agent is an acetate ion, an ascorbate ion, a malate ion or a citrate ion.

22. The method of claim 15 or 16, wherein c') comprises stirring at 90°C to 100°C prior to the refluxing.

23. A magnetic particle or magnetic particle assembly produced by the method of any one of claims 15 to 22.

24. A preparation comprising the magnetic particle according to any one of claims 1 to 5, or the magnetic particle assembly according to any one of claims 6 to 9 or 23, an active ingredient, and optionally an additive.

25. The formulation of claim 24, wherein the formulation is provided in the form of a tablet, capsule, caplet, pill, granule, or liquid.

26. A formulation according to claim 24 or 25, wherein the magnetic particles or magnetic particle aggregates are contained in the formulation in inkjet printed form.

27. A system for detecting ingestion of a medication, comprising: a formulation according to any one of claims 24 to 26; a sensing means for sensing the magnetic field of the formulation; and a detection means for detecting that a subject has taken the formulation based on the sensed magnetic field.

28. The system of claim 27, wherein the detection means detects the amount of the formulation taken by the subject based on the sensed magnetism.

29. The system of claim 28, further comprising: a determining means for determining whether the subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation; and a means for taking an action in response to the result of the determination by the determining means.

30. The system of claim 29, wherein the means for taking an action takes an action in response to determining that the subject has not taken the formulation at the predetermined time or that the subject has not taken the predetermined amount of the formulation, the action including at least one of issuing an alert or sending a message.

31. The system of claim 30, wherein the means for taking an action takes an action in response to determining that the subject has taken the formulation at the predetermined time or that the subject has taken the predetermined amount of the formulation, the action including at least one of sending a message and storing the dosage information in association with a therapeutic effect.

32. A system according to any one of claims 27 to 31, wherein the formulation has information printed thereon by the magnetic particles, and the detection means detects the information based on the sensed magnetism.

33. A method for detecting ingestion of a medication, wherein a preparation to be ingested contains the magnetic particles described in any one of claims 1 to 5 or the magnetic particle assembly described in any one of claims 6 to 9, or is a preparation described in any one of claims 24 to 26, the method comprising: arranging a sensing means for sensing the magnetism of the preparation around a subject; sensing the magnetism of the preparation from within the subject by the sensing means; and detecting that the subject has taken the preparation based on the sensed magnetism.

34. The method of claim 33, comprising: determining whether the subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation; and performing an action in response to determining that the subject has not taken the formulation at the predetermined time or that the subject has not taken the predetermined amount of the formulation.

35. A program for detecting ingestion of a medication, the program being executed in a computer system having a processor, the medication to be taken containing magnetic particles according to any one of claims 1 to 5 or a magnetic particle assembly according to any one of claims 6 to 9, or a medication according to any one of claims 24 to 26, the program causing the processor to perform processes including: receiving a signal representative of the magnetism of the medication sensed by sensing means arranged around the subject; and detecting that the subject has taken the medication of the medication based on the signal representative of the magnetism.

36. The program of claim 35, wherein the processing includes: determining whether the subject has taken the formulation at a predetermined time and / or whether the subject has taken a predetermined amount of the formulation; and taking an action in response to the determination.

37. The program described in claim 35 or 36, wherein the magnetic particles contained in the formulation are printed on the formulation and information is imparted to the formulation by said printing, and the information printed on the formulation is also used in said determination.

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