Magnetic particles used in medication management

Abstract

To provide magnetic particles for use in medication management. [Solution] This disclosure relates to a sensing magnetic probe that enables medication management. The magnetic probe of this disclosure exhibits a magnetic response rate of 5 to 10 times by controlling the production of particles that are relatively small but have an irregular or non-spherical shape. This disclosure also provides a system for detecting medication by using the magnetic particles of this disclosure. The system for detecting medication comprises a drug formulation, sensing means for sensing the magnetism of the drug formulation, and detection means for detecting that a subject has taken the drug formulation based on the sensed magnetism.

Description

[[Technical Field]]

[0001] The present disclosure relates to magnetic particles for use in medication management, a method for producing the same, and applications thereof. [[Background Art]]

[0002] Drug efficacy depends on a patient's compliance with medication. The use of a magnetic probe makes it possible to improve medication compliance. Reasons for leftover medication include self-adjustment, occasional use as needed, forgetting to take medication, duplicate prescriptions, excessive number of days prescribed, adjustment of topical medications, and the like. [[Summary of the Invention]] [[Means for Solving the Problems]]

[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 5 to 10 times higher than conventional products by controllably producing irregular, non-spherical particles even when they are relatively small. The use of the magnetic probe containing the magnetic particles of the present disclosure can prevent self-adjustment and forgetting to take medication, which are causes of leftover medication. The present disclosure is as follows. (Item 1) Magnetic particles having a non-spherical shape. (Item 1B) The magnetic particles according to any one of 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 SEM (scanning electron microscope) or TEM (transmission electron microscope). (Item 2) wherein the magnetic particles have 0.5×10 -3 μT / (mg·nm) or more of magnetic response rate per particle size, the magnetic particles according to any one of the preceding items. (Item 3) The magnetic particles according to any one of the preceding items, wherein the particle diameter of the magnetic particles is 10 nm to 500 nm. (Item 3B) The magnetic particle according to any one of the preceding items, wherein the particle size of the magnetic particle is measured by an image obtained by an electron microscope. (Item 3C) The magnetic particle described in any one of the preceding items, wherein the electron microscope is a scanning electron microscope (SEM) or a transmission electron microscope (TEM). (Item 4) The magnetic particles according to any one of the preceding items, wherein the magnetic particles are iron-containing metallic magnetic particles or iron-containing metal oxide magnetic particles. (Item 5) The magnetic particle according to any one of the preceding items, characterized in that the magnetic particle has a sphericity of 1.1 or higher. (Item 6) Agglomerate is a collection of magnetic particles containing non-spherical magnetic particles. (Item 7) The magnetic particles having a non-spherical shape are those described in any of the preceding items, and the magnetic particle aggregate is as described in any of the preceding items. (Item 8) A magnetic particle aggregate according to any one of the preceding items, wherein the content of the non-spherical magnetic particles is 40% or more of the total magnetic particles. (Item 9) A magnetic particle aggregate according to any one of the preceding items, wherein the content of the non-spherical magnetic particles is 50% or more of the total magnetic particles. (Item 10) A composition comprising a magnetic particle aggregate according to any one of the preceding items, wherein the content of the non-spherical magnetic particles is 50% or more of the composition. (Item 11) A magnetic particle-containing ink containing magnetic particles as described in any one of the preceding items, or an aggregate of magnetic particles as described in any one of the preceding items. (Item 12) The ink is for printing the magnetic particles or the aggregate of magnetic particles onto the surface of a formulation by inkjet, as described in any one of the preceding items. (Item 13) An ink containing magnetic particles as described in any one of the preceding items, further comprising a dye or pigment. (Item 14) A magnetic particle-containing ink according to any one of the preceding items, further comprising a solvent, surfactant, additive, or purified water. (Item 15) A method for producing magnetic particles described in any one of the preceding items, or a collection of magnetic particles described in any one of the preceding items, a) A step of forming a nucleus by hydrolyzing a metal salt with water, b) A step of forming a protective agent around the nucleus by adding a protective agent, c) A step of refluxing a nucleus having the protective agent A method for producing magnetic particles or aggregates of magnetic particles, including [the specified element]. (Item 16) A method for producing magnetic particles described in any one of the preceding items, or a collection of magnetic particles described in any one of the preceding items, a') A step of hydrolyzing a sample containing a metal salt The process involves adding a protective agent to the hydrolysate of b')a') and The process of refluxing the product obtained in c')b') d') A step of selecting and collecting desired magnetic particles or aggregates of magnetic particles as needed. e') A step of classifying particles of a desired particle size as needed. A method of including. (Item 17) The method according to any one of the preceding items, wherein the concentration of the metal salt is 0.04 to 0.06 mol. (Item 18) The method according to any one of the preceding items, wherein the metal salt includes iron chloride, iron bromide, iron perchlorate, or iron hydroxide. (Item 19) The method according to any one of the preceding items, wherein said hydrolysis is achieved by adding water. (Item 20) The method according to any one of the preceding items, wherein said protective agent comprises sodium acetate, sodium ascorbate, sodium malate or sodium citrate. (Item 21) The method according to any one of the preceding items, wherein the moiety imparted to the core by said protective agent is acetate ion, ascorbate ion, malate ion or citrate ion. (Item 22) The method according to any one of the preceding items, wherein said c') comprises a step of stirring at 90°C to 100°C before said refluxing. (Item 23) Magnetic particles or a magnetic particle aggregate produced by the method according to any one of the preceding items. (Item 24) A preparation comprising the magnetic particles according to any one of the preceding items, or the magnetic particle aggregate according to any one of the preceding items, an active ingredient, and optionally an additive. (Item 25) The preparation according to any one of the preceding items, wherein said preparation is provided in the form of a tablet, a capsule, a caplet, a pill, a granule or a liquid. (Item 26) The preparation according to any one of the preceding items, wherein said magnetic particles or said magnetic particle aggregate are contained in said preparation in a form printed by inkjet printing. (Item 26B) The preparation according to any one of the preceding items, wherein said magnetic particles or said magnetic particle aggregate are printed on said medicament so as to include information about the medicament. (Item 26C) The preparation according to any one of the preceding items, wherein said information about the medicament is conveyed by the number or dosage of said magnetic particles. (Item 26D) The preparation according to any one of the preceding items, wherein said information about the medicament comprises visually recognizable information. (Item 27) A system for detecting medication intake, A preparation described in any one of the preceding items, A sensing means for sensing the magnetic field of the preparation, A detection means that detects whether a subject has taken the preparation based on the sensed magnetic field. A system equipped with these features. (Item 28) The detection means is a system according to any one of the preceding items, wherein the detection means detects the amount of the preparation taken by the subject based on the sensed magnetism. (Item 29) A determination means for determining whether the subject has taken the preparation at a predetermined time and / or whether the subject has taken a predetermined amount of the preparation, A means for performing an action in response to the result of the determination by the determination means. A system further comprising any one of the preceding items. (Item 30) The means for performing the aforementioned action performs the action in response to determining that the subject has not taken the preparation at the predetermined time, or that the subject has not taken the predetermined amount of the preparation. The system described in any one of the preceding items, wherein the action includes at least one of issuing an alarm or sending a message. (Item 31) The means for performing the aforementioned action performs the action in response to determining that the subject has taken the preparation at the predetermined time, or that the subject has taken the predetermined amount of the preparation. The system described in any one of the preceding items, wherein the action includes at least one of sending a message or associating and remembering medication information with therapeutic effects. (Item 32) The aforementioned formulation has information printed on it by the magnetic particles, The detection means is a system according to any one of the preceding items, which detects the information based on the sensed magnetism. (Item 33) A method for detecting medication administration, wherein the medication to be administered contains magnetic particles or aggregates of magnetic particles as described in any one of the preceding items, or is a medication as described in any one of the preceding items, and the method is The means for sensing the magnetic field of the preparation is placed around the target, The sensing means detects the magnetism of the preparation from within the object, Based on the detected magnetic field, it is possible to detect that the subject has taken the medication. Methods that include... (Item 34) Determining whether the subject took the preparation at a predetermined time and / or whether the amount of the preparation taken by the subject was a predetermined amount, In response to determining that the subject has not taken the preparation at the predetermined time, or has not taken the predetermined amount of the preparation, an action is taken. The method described in any one of the preceding items, including the method described in the preceding item. (Item 35) A program for detecting medication administration, the program is executed in a computer system equipped with a processor, and the medication to be administered contains magnetic particles or an aggregate of magnetic particles as described in any one of the preceding items, or is a medication as described in any one of the preceding items, and the program is The sensing means arranged around the target receive a signal representing the magnetic field of the preparation that it has detected, Based on the signal representing the magnetic field, it is possible to detect that the subject has taken the preparation. A program that causes the processor to perform a process that includes [a specific function / process]. (Item 36) The aforementioned process is, Determining whether the subject took the preparation at a predetermined time and / or whether the amount of the preparation taken by the subject was a predetermined amount, In response to the determination, an action will be taken. A program that includes any one of the preceding items. (Item 37) The magnetic particles contained in the formulation are printed on the formulation, and information is provided by the printing. In the aforementioned determination, the information printed on the formulation is also used. The program described in any one of the preceding items. In this disclosure, the one or more of the above features are intended to be provided in combinations other than those explicitly stated. Further embodiments and advantages of this disclosure will be apparent to those skilled in the art, by reading and understanding the detailed description below as necessary. [Effects of the Invention]

[0004] By utilizing the results of this research, we were able to improve the magnetic response rate of magnetic particles of approximately 100-200 nm, which conventionally do not have a high magnetic response rate, by controlling their shape and content, resulting in a tenfold improvement. [Brief explanation of the drawing]

[0005] [Figure 1] Figure 1 shows a schematic diagram of a cross-section of a particle with an irregular shape. [Figure 2] Figure 2 shows an example of a program that directs the processor unit to perform the processing required to detect medication intake. [Figure 3] Figure 3 shows an SEM image of the magnetic particles prepared in Example 1. [Figure 4] Figure 4 shows the relationship between the magnetic response coefficient and particle size of the magnetic particles produced in Example 1 and Comparative Example 1. [Figure 5] Figure 5 shows the relationship between magnetic response and sphericity of the magnetic particles prepared in Example 1 and Comparative Example 1. [Modes for carrying out the invention]

[0006] (definition) The present invention will be described in more detail below. Throughout this specification, singular expressions should be understood to include the concept of their plural form unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the" in English) should be understood to include the concept of their plural form unless otherwise specified. Furthermore, terms used herein should be understood to have the meaning commonly used in the art unless otherwise specified. Accordingly, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. In case of any conflict, this specification (including definitions) shall prevail. First, the terms and general techniques used in this invention will be explained.

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

[0008] In this specification, "magnetic particles" refers to particles that possess magnetism, such as ferromagnetic (Fe, Ni, Co, etc.), ferrimagnetic (Fe2O3, MnFe2O4, BAO6Fe2O3, etc.), paramagnetic (Al, Ti, Cu alloys, etc.), and superparamagnetic (Fe3O4, etc.). It includes all magnetic particles, regardless of the degree or type of magnetism. Possible sizes include, but are not limited to, approximately 1 nm to 1000 nm, approximately 1 nm to 800 nm, approximately 1 nm to 600 nm, approximately 1 nm to 400 nm, approximately 10 nm to 1000 nm, approximately 10 nm to 800 nm, approximately 10 nm to 600 nm, and approximately 10 nm to 400 nm.

[0009] In this specification, "iron-containing metallic magnetic particles" means magnetic particles containing iron. Here, iron may also be in the form of ions or salts.

[0010] In this specification, "iron-containing metal oxide magnetic particles" means magnetic particles containing iron oxide (e.g., Fe2O3 and / or Fe3O4).

[0011] In this specification, "circularity" means circularity = (4πS / L 2 Circularity is measured by the following formula: where S is the two-dimensional projected area of ​​the particle and L is the two-dimensional projected perimeter. For measuring circularity, electron microscope images are binarized using image processing, and the circularity can be determined for each individual particle. The two-dimensional projected area of ​​the particle is obtained by determining the area of ​​the particle on the image from the acquired two-dimensional image of the particle. The two-dimensional projected perimeter is measured by taking the acquired two-dimensional image of the particle, including any notches such as edges. The circularity defined in this disclosure refers to the average value of the circularity obtained by measuring 500 randomly selected particles. A circularity of 1.0 indicates a perfect sphere, and a lower value indicates more irregularities on the outer circumference and a higher degree of deformity. For magnetic particles having a non-spherical shape, the circularity is preferably 0.6 or less.

[0012] In this specification, "sphericity" is determined by observing a particle from a microscopic photograph and using the following formula, which is the sum of its circumference and the length of the depression on the particle surface. Sphericity = (Circumference + Sum of the lengths of depressions on the particle surface) / Circumference Here, a depression is determined to exist if (R1-R2) / (R1) is 10% or more, as shown in Figure 1. R1 is the radius of a virtual outer sphere that inscribes the non-spherical particle, and R2 is the radius of a virtual inner sphere whose center is the same as the center of the virtual outer sphere, and whose outer sphere passes through the point closest to the center of the depression. The length of the depression is calculated using R1 - R2. If a single particle has multiple depressions, the lengths of the depressions are added together to calculate the length. As defined in this disclosure, sphericity refers to the average value of sphericity obtained by measuring 500 randomly selected particles. A sphericity of 1.0 indicates a perfect sphere, while a higher value indicates more irregularities on the outer surface and a greater degree of shape distortion.

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

[0014] In this specification, "electron microscope" refers to a microscope that uses a beam of accelerated electrons as a light source for a sample and provides a magnified image. Examples include, but are not limited to, SEM (scanning electron microscope) or TEM (transmission electron microscope). These electron microscopes can be used to measure particle size, roundness, sphericity, etc.

[0015] In this specification, "magnetic particle aggregate" means an aggregate of multiple magnetic particles.

[0016] In this specification, "visible material" means a material that can be seen and, when added, can be used to create color. Examples of visible materials include, but are not limited to, dyes and pigments.

[0017] In this specification, "ink" refers to a colored liquid or suspension used to color a substance. It also refers to a printing method that prints by spraying ink, ejected from a basic spraying structure (architecture) such as an inkjet architecture, onto a substance.

[0018] In this specification, “nucleus” refers to the basic substance used to form particles. For example, the nucleus may be a metal or a metal oxide, and examples of metals or metal oxides include iron, diiron trioxide, or triiron tetroxide, preferably diiron trioxide. Since this disclosure may be used in the pharmaceutical field, in that case, the nucleus may be a pharmaceutically acceptable substance, and preferably a pharmaceutically acceptable metal or metal oxide.

[0019] In this specification, "metal salt" refers to a salt of a metal ion with a free acid. By adding water and hydrolyzing, metal ions can be generated. Examples of metal salts include, but are not limited to, iron chloride, iron bromide, iron perchlorate, and iron hydroxide.

[0020] In this specification, "hydrolysis" is used to refer to a chemical reaction in which water reacts with a compound to produce another compound, and this reaction includes the cleavage of chemical bonds by the addition of hydrogen cations and hydroxide anions derived from water. For example, when hydrolyzing an iron salt, the progress of hydrolysis can be confirmed by using an iron(III) ion titration reagent such as EDTA.

[0021] In this specification, "protective agent" refers to a drug used to protect the nucleus. By using a protective agent, the size growth reaction of the nucleus can be stopped and it can be stabilized in the solvent. Examples of protective agents include, but are not limited to, sodium acetate, sodium ascorbate, sodium malate, or sodium citrate.

[0022] In this specification, the "protective substance" imparted by a "protective agent" refers to a reagent that, when added, can generate a protective substance for protecting the nucleus. Examples of protective substances include, but are not limited to, acetate ions, ascorbate ions, malate ions, or citrate ions.

[0023] In this specification, "medication" means dispensing and giving appropriate medication to a patient, and "medication intake" means the patient taking the medication.

[0024] In this specification, “magnetic” encompasses all elements of magnetism, paramagnetism, and / or ferromagnetism.

[0025] In this specification, “magnetic sensing means” means capable of sensing magnetism and / or changes in magnetic fields. Hereinafter, the sensing means may be a magnetic sensor, etc., and may take the form of a necklace, adhesive sheet (which may be a patch, adhesive adhesive, tape, etc.), strap, clothing, underwear, bra, belt, and suspenders.

[0026] In this specification, “subject” means an animal, such as a mammal (including a human), that has been or will be the target of a treatment, observation, or experiment. The methods described herein may be useful for the treatment and / or veterinary applications in humans. 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 a cat), a livestock animal (e.g., a cattle, a horse, a sheep, a goat, or a pig), and / or an experimental animal (e.g., a mouse, a rat, a hamster, a guinea pig, a pig, a rabbit, a dog, or a monkey). In some embodiments, the subject (or patient) is a human.

[0027] (Preferred embodiment) Preferred embodiments of the Disclosure are described below. The embodiments provided below are provided for a better understanding of the Disclosure, and it will be understood that the scope of the Disclosure should not be limited to the descriptions below. Accordingly, it will be obvious that those skilled in the art can make appropriate modifications within the scope of the Disclosure, taking into consideration the descriptions herein. It will also be understood that the embodiments of the Disclosure below can be used individually or in combination.

[0028] <Magnetic particles> In one aspect, this disclosure provides magnetic particles having a non-spherical shape. By using magnetic particles having a non-spherical shape, magnetic responsiveness can be improved, and magnetic sensors can sensitively detect the magnetic particles. Whether a magnetic particle has a non-spherical shape can be measured by observation with a microscope, circularity, sphericity, or the ratio of theoretical surface areas (R = Adα / 6, where R is the ratio of surface areas, 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 this disclosure is approximately 1 nm to approximately 1000 nm, approximately 1 nm to approximately 800 nm, approximately 1 nm to approximately 600 nm, approximately 1 nm to approximately 400 nm, approximately 10 nm to approximately 1000 nm, approximately 10 nm to approximately 800 nm, approximately 10 nm to approximately 600 nm, or approximately 10 nm to approximately 400 nm, preferably 10 nm to 400 nm. It is preferable that the particle size is suitable for use in inkjet printing.

[0030] In one embodiment, the magnetic particles of this disclosure are iron-containing metal magnetic particles or iron-containing metal oxide magnetic particles. The magnetic particles used in this disclosure are preferably those that do not exhibit toxicity to the human body.

[0031] In one embodiment, the circularity of the magnetic particles of this 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, the magnetic responsiveness 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 greater, 1.02 or greater, 1.03 or greater, 1.04 or greater, 1.05 or greater, 1.06 or greater, 1.07 or greater, 1.08 or greater, 1.09 or greater, or 1.1 or greater. More preferably, the sphericity is 1.1 or greater. By using magnetic particles having a non-spherical shape with a sphericity greater than 1, the magnetic responsiveness can be improved, and the magnetic particles can be detected with high sensitivity by a magnetic sensor.

[0033] <Magnetic particle aggregate> In one aspect, the present disclosure provides a collection of magnetic particles comprising 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 form described in <magnetic particles>.

[0034] In one embodiment, the content of non-spherical magnetic particles of the 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 non-spherical magnetic particles of the Disclosure is preferably 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 inks of the Disclosure contain magnetic particles or aggregates of magnetic particles of the Disclosure and a visible material. It is understood that the various embodiments described herein can be applied in any combination of the forms described in <magnetic particles> and <aggregates of magnetic particles>.

[0036] In one embodiment, the ink of the present disclosure is for printing the magnetic particles or aggregates of magnetic particles of the present disclosure onto the surface of a pharmaceutical formulation by inkjet. By printing on the surface of the pharmaceutical formulation, information about the formulation and a two-dimensional barcode can be inscribed. Because it is printable on the surface of a pharmaceutical formulation, it is also applicable to existing pharmaceutical formulations.

[0037] In one embodiment, the ink of the present disclosure may further comprise a solvent, a surfactant, an additive, purified water, and the like.

[0038] In one embodiment, the ink of the Disclosure contains a visible material, thereby making it visible when printed by inkjet. The inkjet in the Disclosure is selected from the group consisting of dyes, pigments, solvents, surfactants, additives, purified water, and the like.

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

[0040] The surfactants used in this disclosure may include edible surfactants. The surfactants adjust the surface tension of the ink composition to an appropriate range, thereby improving the ink ejection stability. 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, sodium pyrophosphate, and the like. Surfactants may be used alone or in combination of multiple types. The surfactant content is preferably 0.01 to 0.5% by weight in the composition.

[0041] The additives used in this disclosure are various additives commonly used in ink compositions, and may include edible additives. Examples of such additives include chelating agents and antifungal agents. The amount of each is preferably 0.01 to 0.5% by weight in the composition. Chelating agents are particularly 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, diacetyl tartrate monoglyceride, pectin, tamarind gum, xanthan gum, potassium metaphosphate, carboxymethylcellulose, citric acid, hydroxypropylcellulose, polyvinylpyrrolidone, sodium erythorbate, and methylcellulose. These additives may be used individually or in combination. The additive content is preferably 0.05 to 11% by weight in the composition.

[0042] The water used in this disclosure is preferably highly purified water, such as purified water or deionized water. Considering the fluidity of the ink composition, the water content is preferably 20 to 65% by weight, and more preferably 40 to 60% by weight.

[0043] <Manufacturing method> In one aspect, the present disclosure provides a method for producing magnetic particles of the present disclosure or magnetic particle aggregates of the present disclosure. The method for producing magnetic particles of the present disclosure or magnetic particle aggregates of the present disclosure includes 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 combinations of any form described in <Magnetic Particles>.

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

[0045] In one embodiment, the addition of the protective agent can be carried out by any method. Typically, the protective agent is added by adding a solution in which the protective agent is dissolved in a suitable reaction solvent. While we do not wish to be bound by theory, the addition of a protective agent causes the protective substance components contained in the agent to interact with the nucleus, forming a protective substance around the nucleus. This formation around the nucleus may occur via covalent or non-covalent bonds (e.g., ionic bonds, hydrophobic bonds, etc.).

[0046] In one embodiment, reflux of nuclei with a protective agent can typically be performed by heating a suitable reaction solvent to reflux temperature.

[0047] In one aspect, the Disclosure provides a method for producing magnetic particles of the Disclosure or aggregates of magnetic particles of the Disclosure. a') A step of hydrolyzing a sample containing a metal salt The process involves adding a protective agent to the hydrolysate of b')a') and The process of refluxing the product obtained in c')b') d') A step of selecting and collecting desired magnetic particles or aggregates of magnetic particles as needed. e') A step of classifying particles of a desired particle size as needed. It is understood that the various embodiments described herein can be applied by appropriately combining any form described in <Magnetic Particles>.

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

[0049] In one embodiment, the addition of the protective agent can be carried out in any manner. While we do not wish to be bound by theory, it is preferable that the addition of the protective agent be carried out under conditions in which the protective substance is formed around the nucleus. The conditions for the formation of the protective substance can usually be achieved by mixing the protective agent with the nucleus in a suitable reaction solvent.

[0050] In one embodiment, reflux of the nuclei with the protective agent can usually be carried out by heating a suitable reaction solvent to reflux temperature, preferably under conditions that form 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 used at a high concentration, for example, 0.02-0.1 mol, 0.02-0.09 mol, 0.02-0.08 mol, 0.02-0.07 mol, 0.02-0.06 mol, 0.02-0.05 mol, 0.02-0.04 mol, 0.02-0.03 mol, 0.03-0.1 mol, 0.03-0.09 mol, 0.03-0.08 mol, 0.03-0.07 mol, 0.03-0.06 mol, 0.03-0.05 mol, 0.03-0.04 mol, 0.04-0.1 mol The concentrations are 0.04-0.09 mol, 0.04-0.08 mol, 0.04-0.07 mol, 0.04-0.06 mol, 0.04-0.05 mol, 0.05-0.1 mol, 0.05-0.09 mol, 0.05-0.08 mol, 0.05-0.07 mol, 0.05-0.06 mol, 0.06-0.1 mol, 0.06-0.09 mol, 0.06-0.08 mol, 0.06-0.07 mol, 0.07-0.1 mol, 0.07-0.09 mol, 0.07-0.08 mol, 0.08-0.1 mol, 0.08-0.09 mol, and 0.09-0.1 mol. Preferably, the concentration of the metal salt is 0.04-0.06 mol. By using high concentrations, the probability of collisions between metal salts can be increased, thereby improving the probability of forming magnetic particles with a non-spherical shape.

[0052] In one embodiment, the metal salt of the present disclosure may be any salt that forms a metal group ion upon hydrolysis, preferably an iron salt. More preferably, it may be iron chloride, iron bromide, iron perchlorate, or iron hydroxide.

[0053] In one embodiment, hydrolysis in step a) or step a') is achieved by adding water. The concentration of water used for hydrolysis in step a) or step a') is high, for example, 0.1-1 mol, 0.1-0.9 mol, 0.1-0.8 mol, 0.1-0.7 mol, 0.1-0.6 mol, 0.1-0.5 mol, 0.1-0.4 mol, 0.1-0.03 mol, 0.1-0.02 mol, 0.2-1 mol, 0.2-0.9 mol, 0.2-0.8 mol, 0.2-0.7 mol, 0.2-0.6 mol, 0.2-0.5 mol, 0.2-0.4 mol, 0.2-0.3 mol, 0.3-1 mol, 0.3-0.9 mol, 0.3-0.8 mol, 0. The concentrations are 3-0.7 mol, 0.3-0.6 mol, 0.3-0.5 mol, 0.3-0.4 mol, 0.4-1 mol, 0.4-0.9 mol, 0.4-0.8 mol, 0.4-0.7 mol, 0.4-0.6 mol, 0.4-0.5 mol, 0.5-1 mol, 0.5-0.9 mol, 0.5-0.8 mol, 0.5-0.7 mol, 0.5-0.6 mol, 0.6-1 mol, 0.6-0.9 mol, 0.6-0.8 mol, 0.6-0.7 mol, 0.7-1 mol, 0.7-0.9 mol, 0.7-0.8 mol, 0.8-1 mol, 0.8-0.9 mol, and 0.9-1 mol. Preferably, the concentration of water is 0.4-0.6 mol. By using it at high concentrations, the probability of collisions between metal ions generated by hydrolysis can be increased, thereby improving the probability of forming magnetic particles with a non-spherical shape.

[0054] In one embodiment, hydrolysis in step a) or step a') is achieved by heating. The hydrolysis temperature used in step a) or step 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, it is achieved at 70°C to 80°C. Heating activates the movement of the material and increases collision energy, thereby increasing the probability of metal ions colliding and improving the probability of forming magnetic particles with a non-spherical shape.

[0055] In one embodiment, the protective agent of this disclosure is sodium acetate, sodium ascorbate, sodium malate, or sodium citrate. By using a protective agent, the size growth reaction of the nuclei during nucleation can be controlled and stabilized in the solvent. Furthermore, the particles can be made monodisperse, enabling the production of smaller particles.

[0056] In one embodiment, step b) or b') of the present disclosure includes adding a protective agent and then heating and stirring. The heating temperature 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, 80°C to 100°C, 80°C to 90°C, or 90°C to 100°C. Preferably, it is 90°C to 100°C. Heating can promote the reduction reaction from metal ions to metal, and further promote the formation of bonds between the protective agent and iron.

[0057] In one embodiment, in step b) or step b'), it is possible to confirm that the protective agent has bound to the magnetic particles or their nuclei by electrophoresis or zeta potential measurement. Furthermore, changes in the binding state of the protective agent can be confirmed using X-ray photoelectron spectroscopy (XPS) or infrared absorption spectroscopy (IR).

[0058] In one embodiment, step c') of the present disclosure includes heating and stirring before reflux. The temperature during heating 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. This can activate the movement of the material and increase collision energy, thereby increasing the probability of metal ions colliding and improving the probability of forming magnetic particles having a non-spherical shape.

[0059] In one embodiment, step d') of the present disclosure includes the steps of collecting magnetic particles and sorting the desired magnetic particles or aggregate of magnetic particles. By sorting the particles, only the nanoparticles with higher magnetism can be extracted.

[0060] <Pharmaceutical Products> In one aspect, the Disclosure provides formulations comprising magnetic particles of the Disclosure, magnetic particle aggregates of the Disclosure, an active ingredient, and optionally an additive. It is understood that the various embodiments described herein can be applied in any combination of the forms described herein as appropriate, such as <magnetic particles>, <magnetic particle aggregates>, and <inks>. In the Disclosure, "active ingredient" is used in the same sense as it is commonly used in the Art, and means any ingredient that is effective in treating or preventing a disease, disorder, or condition for which the treatment or prevention is the objective.

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

[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 liquid formulations.

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

[0064] In one embodiment, information about the formulation of the Disclosure may include the type of formulation (e.g., active ingredients and optionally additives), dosage and / or method of use. This information is conveyed by printing on the formulation with an ink containing magnetic particles or aggregates of magnetic particles of the Disclosure.

[0065] In one embodiment, information about the formulation of the present disclosure, such as the number of particles and dosage, is transmitted by detecting the magnetic information of the magnetic particles. By sensing the magnetic information, it is possible to prevent missed doses, overdoses, and incorrect medication intake, to check for drug combinations (contraindications), to check for expiration dates (lot number), to reduce the burden on caregivers, and to improve the efficiency of managing remaining medication.

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

[0067] Depending on the purpose, these additives may include excipients, disintegrants, binders, fluidizers, lubricants, coating agents, solvents, solubilizers, thickeners, dispersants, stabilizers, sweeteners, flavorings, etc. Specific examples of these additives, though not limited to these, include 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, stearyl sodium fumarate, polyethylene glycol, propylene glycol, titanium dioxide, talc, and the like.

[0068] In one embodiment, the information of the formulation of the present disclosure includes visually recognizable information.

[0069] (Example of combination) (Method for producing magnetic particles according to this disclosure) The following examples illustrate the manufacturing method of the magnetic particles described herein, but are not limited to these examples. Representative schemes are described below, but the disclosure is not limited to these.

[0070] The magnetic particles of this disclosure can be manufactured, for example, by the manufacturing methods described below. These manufacturing 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 mixture is heated and stirred. Then, a protective agent such as sodium acetate is added, and the mixture is heated and stirred. Finally, reflux is performed to generate magnetic particles.

[0071] (Application) The magnetic particles, magnetic particle aggregates, inks, formulations printed with magnetic particles, or medication systems disclosed herein can be used for any application, for example, in the development of tablet inks, detection devices, medication management systems, etc. The methods disclosed herein provide magnetic particles, magnetic particle aggregates, inks, formulations printed with magnetic particles, or medication systems for these applications. Preferably, a special material can be printed on the surface of a tablet by high-speed inkjet printing of magnetic nanoparticles, enabling sensing by smart necklaces, etc., and allowing tablet type identification by sensors. Alternatively, it can provide services to patients, families, and healthcare professionals, enabling individualized support through combined analysis of vital information, and enabling notification of the effects of medication.

[0072] While we do not wish to be bound by theory, the formulation or drug delivery system described herein may offer unprecedented advantages in terms of safety, cost, and versatility. For example, in vivo safety is guaranteed, and it is significantly safer than cases where chips are embedded in tablets. In terms of cost, it can be mass-produced simply and inexpensively, without increased costs due to the difficulty of production. In terms of versatility, it does not require major prescription changes, the regulatory hurdles are low, and under Japanese regulations, it is judged that changes can be made with only a minor change notification. Furthermore, it can be applied to existing drugs, which is an advantage compared to technologies that have high cost and regulatory hurdles and are difficult to apply to various drugs.

[0073] (Example of a medication management system) The medication detection system of this disclosure (which may also be referred to as the medication system in this specification) 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 or patching a detection device (e.g., a necklace-type detection device or a patch-type detection device) capable of detecting the magnetic particle aggregate of this disclosure to a site on the subject's digestive tract where detection is possible (e.g., the subject's neck or chest). The information of this disclosure can be combined with vital data, activity data, dietary data, sleep data, etc., for each subject to provide data on the effects of medication tailored to each subject's lifestyle.

[0074] <Medication Management System> In one aspect, the Disclosure provides a system for detecting medication administration. The system comprises a formulation of the Disclosure, a sensing means for sensing the magnetic field of the formulation, and a detection means for detecting, based on the sensed magnetic field, that a subject has administered the formulation. It is understood that the various embodiments described herein can be applied in any combination of the forms described in <magnetic particles>, <magnetic particle aggregates>, and <inks>. Unless otherwise specified, “formulation” as used herein means “formulation” as described herein.

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

[0076] In one embodiment, the detection means of the present disclosure detects the amount of a drug administered to a subject based on a sensed magnetic field. For example, the detection means may use a function that defines the relationship between the intensity of the sensed magnetic field and the amount of drug administered to detect the amount of drug administered to the subject, or it may use a lookup table that defines the relationship between the intensity of the sensed magnetic field and the amount of drug administered to detect the amount of drug administered to the subject, or it may use machine learning to detect the amount of drug administered to the subject. When machine learning is used to detect the amount of drug administered, the machine learning model used learns the relationship between the intensity of the magnetic field and the amount of drug administered to the subject. For example, it learns data from multiple trials, using the intensity of the magnetic field as input training data and the amount of drug administered 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 determination means for determining whether a subject has taken a formulation at a predetermined time and / or whether a subject has taken a predetermined amount of the formulation, and means for taking an action in response to the result of the determination by the determination means.

[0078] The determination means can communicate with the detection means and receive information from the detection means regarding whether the subject has taken the preparation. The information regarding whether the subject has taken the preparation may include at least one of the following: the fact that the subject took the preparation, the amount of the preparation taken by the subject, and information printed on the preparation taken by the subject.

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

[0080] The determination means identifies the amount of the preparation taken by the subject based on information received from the detection means, for example. By determining whether the identified amount is a predetermined amount, it is possible to determine whether the subject has taken a predetermined amount of the preparation. For example, if the subject is instructed to take one tablet of the preparation per dose, the determination means will determine whether the identified amount of the preparation 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 detect chewing and swallowing status, blood glucose levels, body temperature, pulse, blood oxygen saturation, and whether the person is lying down). Information obtained from other sensors that can be used by acquiring it simultaneously with or in parallel with medication administration includes, for example, • Breathing, voice, eye movements, excretion, facial expressions ·Location information • Steps, walking speed, activity level, meals, calorie intake • Vital data (heart rate, blood pressure, blood glucose level, blood flow, blood oxygen saturation, sleep data, electroencephalogram, weight, body temperature, basal body temperature) • Electronic medical record data, health checkup / medical examination data These are some examples, but are not limited to them. By combining medication data with the above information, it can be used from the patient's perspective to visualize treatment effects and motivate them, and from the perspective of healthcare professionals and caregivers to visualize treatment effects as well as for disease management, recurrence prevention, and prognosis management.

[0082] In one embodiment, the means for performing the action of the present disclosure may take action in response to the determination that the subject has not taken the formulation at a predetermined time or has not taken the predetermined amount of the formulation. This is the case when the subject has not taken the formulation as instructed, i.e., poor medication compliance. Therefore, the action in this case may be to encourage medication. For example, the action may be to issue an alarm, in which case the means for performing the action may be an alarm-issuing means. The alarm may be issued visually (e.g., by light), aurally (e.g., by an alarm sound), tactilely (e.g., by vibration), or olfactorily (e.g., by smell). For example, the action may be to send a message, in which case the means for performing the action may be a communication means. The message may be, for example, a message encouraging the subject to take medication, and may be sent to the subject's information terminal. The message could be, for example, a message informing that the subject has not taken their medication, and could be sent to people around the subject (e.g., family members, attending physician, nurse, caregiver, etc.). Here, the information terminal includes, but is not limited to, mobile phones, smartphones, tablets, smartwatches, smart glasses, personal computers, smart speakers, and smart TVs.

[0083] In one embodiment, the means for performing the action of the present disclosure can perform the action in response to the determination that the subject has taken the formulation at a predetermined time or that the subject has taken a predetermined amount of the formulation. This is the case when the subject is taking the formulation as instructed, i.e., when medication compliance is good. Therefore, the action in this case may be for maintaining motivation to take the medication. For example, the action may be sending a message, in which case the means for performing the action may be a communication means. The message may be, for example, a message praising the subject for taking the medication, and may be sent to the subject's information terminal. The message may be, for example, a message informing the subject that they have taken the medication, and may be sent to people around the subject (e.g., the subject's family, attending physician, nurse, caregiver, etc.). For example, the action may be for associating and remembering medication information with therapeutic effects, in which case the means for performing the action may be a memory means. For example, records of medication would be stored in a medication diary, etc.

[0084] In one embodiment, the formulation of the present disclosure has information printed on it by magnetic particles, and a detection means detects the information based on the sensed magnetism. More specifically, the formulation has information about the type of drug, dosage and / or how to use it printed on it by magnetic particles, and a detection means can receive a signal from a magnetic sensor to detect the intensity of the magnetism, the distribution (location) of the magnetism, and the type of magnetism.

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

[0086] The sensing means for detecting the magnetism of the above-mentioned formulation can be implemented by a magnetic sensor. The magnetic sensor is configured 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 by wireless connection.

[0087] An information processing device can be any device capable of processing information, and is typically a mobile phone, smartphone, tablet, smartwatch, or personal computer, and preferably the device is a portable device.

[0088] The information processing device comprises an interface unit, a processor, and 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 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 signals to the information processing device via the interface unit. For example, a terminal device of a target or a person in the vicinity of a target can communicate with the information processing device via the interface unit.

[0090] The interface unit includes, for example, an input unit that enables information to be input to the information processing device. The manner in which the input unit enables information to be input to the information processing device is not limited. For example, if the input unit is a receiver, the receiver may input information by receiving it 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 it 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 the output of information from the information processing device. The mode by which the output unit enables the output of information from the information processing device is not limited. For example, if the output unit is a display, it may output information by displaying a screen on the display. For example, if the output unit is a speaker, it may output sound externally. For example, if the output unit is a data writing device, it may output information by writing information to a storage medium connected to the information processing device. Alternatively, if the output unit is a transmitter, it may output information by the transmitter transmitting information outside the information processing device via a network.

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

[0093] Memory stores programs necessary for executing the processing of an information processing device, as well as data necessary for the execution of those programs. Memory may also store a program that causes the processor to perform processing for detecting medication (for example, a program that implements the processing shown in Figure 2). Here, it is not relevant how the program is stored in memory. For example, the program may be pre-installed in memory. Alternatively, the program may be installed in memory by being downloaded via a network. Alternatively, the program may be stored in a non-transient computer-readable storage medium. Memory can be implemented by any storage means.

[0094] For example, the detection means and determination means described above can be implemented by the processor of the information processing device. For example, the means for performing the actions described above can be implemented by the processor of the information processing device, or by the processor and interface unit. Alternatively, the means for performing the actions 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 Figure 2. First, the sensing device receives a signal representing the magnetic field of the detected drug. Next, based on the magnetic field signal, it detects that the subject has taken the drug. Then, it confirms whether the subject took the drug as instructed. If the subject took the drug as instructed, it issues instructions to take actions to maintain the subject's motivation to take the drug as instructed. If the subject did not take the drug as instructed, it issues instructions to take actions to encourage the subject to take the drug as instructed.

[0096] In one embodiment, a method for detecting administration of the present disclosure, wherein the administered preparation comprises magnetic particles or aggregates of magnetic particles of the present disclosure, or is a preparation of the present disclosure, the method comprising: placing a sensing means for sensing the magnetism of the preparation around an object; sensing the magnetism of the preparation from within the object using the sensing means; and detecting, based on the sensed magnetism, that the object has administered the preparation.

[0097] In one embodiment, the method includes determining whether a subject of the Disclosure 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 taking action in response to the determination that the subject has not taken the formulation at the predetermined time or has not taken the predetermined amount of the formulation.

[0098] In one embodiment, a program for detecting the administration of the present disclosure is provided. The program is executed in a computer system having a processor, and the administered formulation comprises magnetic particles or aggregates of magnetic particles of the present disclosure, or is a formulation of the present disclosure. The program of the present disclosure can also cause the processor to perform a process that includes receiving a signal representing the magnetism of the formulation sensed by sensing means positioned around the subject, and detecting, based on the signal representing the magnetism, that the subject has administered the formulation.

[0099] In one embodiment, the processing of the present disclosure includes determining whether a 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 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 them by printing, and the information printed on the formulation is also used in the determination.

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

[0102] The following provides examples of how this disclosure can be implemented, but this disclosure is by no means limited to these examples. Specifically, the reagents used are those described in the examples, but equivalent products from other manufacturers (Sigma-Aldrich, Wako Pure Chemical Industries, Nakarai, etc.) can be substituted.

[0103] (Example 1: Preparation of magnetic particles) Details are as follows: (procedure) FeCl3·6H2O was dissolved in ethylene glycol. The resulting 0.04 mol FeCl3·6H2O·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 kept warm and stirred at 70°C for a further 60-120 minutes. Next, sodium acetate was added, and the mixture was stirred at 100°C for 1 hour, followed by reflux for 50-80 hours. The formation of magnetic particles was determined by observing the change in the solution's color from brown to black. The obtained magnetic particles were classified by particle size using methods known in the field.

[0104] (Comparative Example 1: Confirmation of Size Effect) As raw materials, iron trichloride hexahydrate (FeCl3·6H2O), sodium acetate (CH3COONa), and distilled water (H2O) were dissolved in ethylene glycol in the molar amounts listed in Table 1 below. 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 proportion of the raw materials introduced (molar amount: mol. In the table, the amounts for iron trichloride, sodium acetate, and distilled water are in moles), and the results are summarized in Table 1.

[0105] [Table 1]

[0106] (Example 2: Evaluation of magnetic particles) Electron microscope images were obtained using a scanning electron microscope (SEM) for the magnetic particles prepared in Example 1 (Figure 3). 500 particles were analyzed from the obtained electron microscope images to measure their particle size and sphericity. Next, the magnetism of the magnetic particles obtained in Example 1 and Comparative Example 1 was measured. The magnetism was measured using a magnetic sensor. By dividing the obtained magnetism by the mass of the measured magnetic particle, the magnetic response rate (slope of the calibration curve) (mT / g) was obtained. The magnetic response rate and particle size of the magnetic particles prepared in Example 1 and Comparative Example 1 are summarized in Figure 4. The magnetic response rate and sphericity of the magnetic particles prepared in Example 1 and Comparative Example 1 are summarized in Figure 5. The magnetic response rate and sphericity of the magnetic particles prepared in Example 1 and Comparative Example 1 are summarized in Table 2.

[0107] [Table 2]

[0108] (Example 3: Preparation of magnetic particle-containing ink) The magnetic particle-containing ink of this disclosure is prepared using a method similar to that described in Japanese Patent Application Publication No. 2016-37566. The magnetic particles, solvent, surfactant, and additive 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 the ink composition.

[0109] (Example 4: Preparation of a formulation containing magnetic particles) A formulation containing magnetic particles is prepared by printing tablets using an inkjet printer with the ink composition obtained in the above example.

[0110] (Example 5: Animal experiment) A dog or monkey equipped with a magnetic sensor is orally administered the magnetic particle-containing formulation of this disclosure. Subsequently, a comparison can be made between the placebo and the magnetic particle-containing formulation to evaluate the drug management of the magnetic particle-containing formulation of this disclosure as it passes through the bodies of dogs or monkeys.

[0111] (Example 6: Human application: Example of administration) The magnetic particle-containing formulation described herein is administered to a person wearing a magnetic sensor. Data from the magnetic sensor is analyzed to determine the type of formulation administered, the amount administered, and the timing of administration. If the type of formulation, the amount administered, and the timing of administration can be measured, it can be widely used in medication management systems. Therefore, it is possible to measure which of multiple formulations was taken, when, and in what quantity. By combining this with vital data, activity data, dietary data, sleep data, etc., the effects of medication tailored to a person's lifestyle can be analyzed.

[0112] (Note) As described above, while the present disclosure has been illustrated using preferred embodiments thereof, it is understood that the scope of this disclosure should be interpreted solely by the claims. Patents, patent applications and other documents cited herein should be incorporated herein by reference as if their contents were specifically described herein. [Industrial applicability]

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

Claims

1. Magnetic particles having a non-spherical shape.

2. The magnetic particles are 0.5 × 10 －３ The magnetic particle according to claim 1, characterized by having a magnetic response coefficient / particle size of μT / (mg・nm) or greater.

3. The magnetic particle according to claim 1 or 2, wherein the particle size of the magnetic particle 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 metallic magnetic particles or iron-containing metal oxide magnetic particles.

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

6. A collection of magnetic particles containing magnetic particles with a non-spherical shape.

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

8. The magnetic particle aggregate according to claim 6 or 7, wherein the content of the non-spherical magnetic particles is 40% or more of the total magnetic particles.

9. A magnetic particle aggregate according to any one of claims 6 to 8, wherein the content of the non-spherical magnetic particles is 50% or more of the total magnetic particles.

10. A composition comprising a magnetic particle aggregate according to claims 6 to 9, wherein the content of the non-spherical magnetic particles is 50% or more of the composition.

11. A magnetic particle-containing ink comprising magnetic particles according to any one of claims 1 to 5, or a collection of magnetic particles 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 aggregate of magnetic particles onto the surface of a pharmaceutical product by inkjet.

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

14. A 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 magnetic particles according to any one of claims 1 to 5, or a magnetic particle aggregate according to any one of claims 6 to 9, a) A step of forming a nucleus by hydrolyzing a metal salt with water, b) A step of forming a protective agent around the nucleus by adding a protective agent, c) A step of refluxing the nucleus having the protective agent. A method for producing magnetic particles or aggregates of magnetic particles, including [the specified element].

16. A method for producing magnetic particles according to any one of claims 1 to 5, or a magnetic particle aggregate according to any one of claims 6 to 9, a') A step of hydrolyzing a sample containing a metal salt The process involves adding a protective agent to the hydrolysate of b') a') and The process of refluxing the product obtained in c') b') d') A step of selecting and collecting desired magnetic particles or aggregates of magnetic particles as needed. e') A step of classifying particles of a desired particle size as needed. A method of including.

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

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

19. The method according to claim 15 or 16, wherein the hydrolysis is achieved by adding water.

20. The method according to claim 15 or 16, wherein the protective agent comprises sodium acetate, sodium ascorbate, sodium malate, or sodium citrate.

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

22. The method according to claim 15 or 16, wherein c') includes a step of stirring at 90°C to 100°C before reflux.

23. Magnetic particles or aggregates of magnetic particles manufactured by the method described in any one of claims 15 to 22.

24. A formulation comprising magnetic particles according to any one of claims 1 to 5, or a collection of magnetic particles according to any one of claims 6 to 9 or 23, an active ingredient, and optionally an additive.

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

26. The formulation according to claim 24, wherein the magnetic particles or aggregate of magnetic particles are included in the formulation in a form printed by inkjet.

27. A system for detecting medication intake, A preparation according to any one of claims 24 to 26, A sensing means for sensing the magnetic field of the preparation, A detection means that detects whether a subject has taken the preparation based on the sensed magnetic field. A system equipped with these features.

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

29. A determination means for determining whether the subject took the preparation at a predetermined time and / or whether the subject took a predetermined amount of the preparation, A means for performing an action in response to the result of the determination by the determination means. The system according to claim 28, further comprising:

30. The means for performing the aforementioned action performs the action in response to determining that the subject has not taken the preparation at the predetermined time, or that the subject has not taken the predetermined amount of the preparation. The system according to claim 29, wherein the action includes at least one of issuing an alarm and sending a message.

31. The means for performing the aforementioned action performs the action in response to determining that the subject has taken the preparation at the predetermined time, or that the subject has taken the predetermined amount of the preparation. The system according to claim 30, wherein the action includes at least one of sending a message and associating and storing medication information with therapeutic effects.

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

33. A method for detecting medication administration, wherein the administered preparation comprises magnetic particles according to any one of claims 1 to 5 or a collection of magnetic particles according to claims 6 to 9, or the preparation according to claims 24 to 26, and the method is The means for sensing the magnetic field of the preparation is placed around the target, The sensing means detects the magnetism of the preparation from within the object, Based on the detected magnetic field, it is possible to detect that the subject has taken the medication. Methods that include...

34. Determining whether the subject took the preparation at a predetermined time and / or whether the amount of the preparation taken by the subject was a predetermined amount, In response to determining that the subject has not taken the preparation at the predetermined time, or has not taken the predetermined amount of the preparation, an action is taken. The method according to claim 33, including the method described in claim 33.

35. A program for detecting medication administration, the program is executed in a computer system equipped with a processor, and the administered preparation comprises magnetic particles according to any one of claims 1 to 5 or a collection of magnetic particles according to claims 6 to 9, or the preparation according to claims 24 to 26, and the program is The sensing means arranged around the target receive a signal representing the magnetic field of the preparation that it has detected, Based on the signal representing the magnetic field, it is possible to detect that the subject has taken the preparation. A program that causes the processor to perform a process that includes [a specific function / process].

36. The aforementioned process is, Determining whether the subject took the preparation at a predetermined time and / or whether the amount of the preparation taken by the subject was a predetermined amount, In response to the determination, an action will be taken. The program according to claim 35, including the program described in claim 35.

37. The magnetic particles contained in the formulation are printed on the formulation, and information is provided by the printing. In the aforementioned determination, the information printed on the formulation is also used. The program according to claim 35 or 36.

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