WO2025023260A1 - Magnetic particles used for medication management - Google Patents

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

This disclosure relates to magnetic particles for use in medication management, their manufacturing method, and their applications.

Drug efficacy depends on the patient's compliance with medication. Using a magnetic probe can improve compliance. Reasons for leftover medication include self-regulation, taking medication as needed, forgetting to take a dose, duplicate prescriptions, excessive prescription dates, and adjustments to topical medications.

The present disclosure relates to a sensing magnetic probe that enables medication management. The magnetic probe of the present disclosure shows a magnetic response rate of 5 to 10 times by controlling the production of particles with irregular shapes and non-spherical shapes, even if they are relatively small. By using a magnetic probe containing the magnetic particles of the present disclosure, it is possible to prevent self-regulation and forgetting to take medication, which are the causes of leftover medication.
The present disclosure is as follows.
(Item 1)
Magnetic particles having a non-spherical shape.
(Item 1B)
The magnetic particle according to the preceding item, wherein the non-spherical shape is determined by images obtained by electron microscopy.
(Item 1C)
13. The magnetic particle of any one of the preceding claims, wherein the non-spherical shape is determined by SEM (scanning electron microscope) or TEM (transmission electron microscope).
(Item 2)
Item 11. The magnetic particles according to any one of the preceding items, characterized in that the magnetic particles have a magnetic response rate/particle size of 0.5×10 ⁻³ μT/(mg·nm) or more.
(Item 3)
10. The magnetic particle of any one of the preceding claims, wherein the particle size of the magnetic particle is between 10 nm and 500 nm.
(Item 3B)
10. The magnetic particle of claim 1, wherein the particle size of the magnetic particle is measured by an image obtained by an electron microscope.
(Item 3C)
Item 11. Magnetic particles according to any one of the preceding items, wherein the electron microscope is a SEM (scanning electron microscope) or a TEM (transmission electron microscope).
(Item 4)
10. The magnetic particle of any one of the preceding items, wherein the magnetic particle is an iron-containing metal magnetic particle or an iron-containing metal oxide magnetic particle.
(Item 5)
10. The magnetic particle according to claim 9, wherein the magnetic particle has a sphericity of 1.1 or more.
(Item 6)
A magnetic particle agglomerate comprising magnetic particles having a non-spherical shape.
(Item 7)
Item 11. The magnetic particle assembly according to any one of the preceding items, wherein the magnetic particles having a non-spherical shape are as defined in any one of the preceding items.
(Item 8)
2. The magnetic particle assembly according to any one of the preceding items, wherein a content of the magnetic particles having a non-spherical shape is 40% or more with respect to the total amount of magnetic particles.
(Item 9)
Item 10. The magnetic particle assembly according to any one of the preceding items, wherein a content of the magnetic particles having a non-spherical shape is 50% or more with respect to the total amount of magnetic particles.
(Item 10)
13. A composition comprising the magnetic particle assembly according to any one of the preceding items, wherein the content of said magnetic particles having a non-spherical shape is 50% or more relative to the composition.
(Item 11)
A magnetic particle-containing ink 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.
(Item 12)
10. The magnetic particle-containing ink of any one of the preceding items, wherein the ink is for printing the magnetic particles or the magnetic particle aggregates on a formulation surface by inkjet.
(Item 13)
13. The magnetic particle-containing ink of any one of the preceding items, further comprising a dye or pigment.
(Item 14)
13. The magnetic particle-containing ink of any one of the preceding items, further comprising a solvent, a surfactant, an additive or purified water.
(Item 15)
A method for producing a magnetic particle according to any one of the preceding items or a magnetic particle assembly according to any one of the preceding items, comprising the steps of:
a) forming nuclei by hydrolyzing a metal salt with water;
b) adding a protective agent to form a protective agent around the core;
and c) refluxing the cores with said protecting agent.
(Item 16)
A method for producing a magnetic particle according to any one of the preceding items or a magnetic particle assembly according to any one of the preceding items, comprising the steps of:
A method 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') optionally selecting and collecting desired magnetic particles or magnetic particle aggregates; and e') optionally classifying particles of a desired particle size.
(Item 17)
13. The method of any one of the preceding items, wherein the concentration of the metal salt is from 0.04 mol to 0.06 mol.
(Item 18)
2. 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)
8. The method of any one of the preceding items, wherein the hydrolysis is accomplished by adding water.
(Item 20)
13. 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 according to any one of the preceding items, wherein the moiety attached to the nucleus by the protecting agent is an acetate ion, an ascorbate ion, a malate ion or a citrate ion.
(Item 22)
The method of any one of the preceding items, wherein c') comprises stirring at 90°C to 100°C prior to said refluxing.
(Item 23)
A magnetic particle or magnetic particle collection produced by the method according to any one of the preceding items.
(Item 24)
A formulation comprising the magnetic particle according to any one of the preceding items, or the magnetic particle assembly according to any one of the preceding items, an active ingredient, and optionally an additive.
(Item 25)
The formulation of any one of the preceding claims, wherein the formulation is provided in the form of a tablet, capsule, caplet, pill, granule, or liquid.
(Item 26)
10. The formulation of any one of the preceding claims, wherein the magnetic particles or magnetic particle aggregates are included in the formulation in inkjet printed form.
(Item 26B)
13. The formulation of any one of the preceding claims, wherein the magnetic particles or magnetic particle aggregates are printed on the medication to contain information about the medication.
(Item 26C)
The formulation of any one of the preceding claims, wherein information about the drug is conveyed by the number or dose of the magnetic particles.
(Item 26D)
The formulation of any one of the preceding claims, wherein the medication information comprises visually perceptible information.
(Item 27)
1. A system for detecting medication ingestion, comprising:
A formulation according to any one of the preceding items;
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 magnetism.
(Item 28)
11. The system of claim 1, wherein the detection means detects the amount of the formulation taken by the subject based on the sensed magnetism.
(Item 29)
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;
7. The system of any one of the preceding claims, further comprising: means for taking an action in response to a result of the determination by the determining means.
(Item 30)
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;
11. The system of any one of the preceding items, wherein the action includes at least one of raising an alarm and sending a message.
(Item 31)
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 system of any one of the preceding claims, wherein the action includes at least one of sending a message and storing medication information in association with a therapeutic effect.
(Item 32)
The formulation has information printed thereon by the magnetic particles,
13. The system of claim 1, wherein the detection means detects the information based on the sensed magnetism.
(Item 33)
A method for detecting ingestion, the formulation to be administered comprises a magnetic particle or a magnetic particle assembly as described in any one of the preceding items, or is a formulation as described in any one of the preceding items, the method comprising:
placing a sensing means for sensing the magnetic field of the formulation around the subject;
sensing the magnetic field of the formulation from within the subject with the sensing means;
and detecting that the subject has ingested the formulation based on the sensed magnetism.
(Item 34)
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;
The method of any one of the preceding items, comprising 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.
(Item 35)
A program for detecting ingestion, the program being executed in a computer system having a processor, the formulation to be administered comprising the magnetic particles or the magnetic particle assembly of any one of the preceding items, or the formulation of any one of the preceding items, the program comprising:
receiving a signal representative of the magnetic properties of the formulation as sensed by sensing means disposed about the subject;
and detecting that the subject has taken the formulation based on a signal representing the magnetism.
(Item 36)
The process comprises:
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;
7. The program of claim 1, further comprising: performing an action in response to the determining.
(Item 37)
The magnetic particles contained in the preparation are printed on the preparation, and information is imparted to the magnetic particles by the printing.
In the determination, information printed on the formulation is also used.
13. A program according to any one of the preceding items.
It is contemplated that the present disclosure may provide one or more of the above 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.

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 about 100 nm to 200 nm, which previously had low magnetic response rates.

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

(Definition)
The present invention will now be described in further detail.
Throughout this specification, the expression of the singular form should be understood to include the concept of the plural form, unless otherwise specified. Therefore, the singular article (e.g., in the case of English, "a", "an", "the", etc.) should be understood to include the concept of the plural form, 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 field, unless otherwise specified. Therefore, unless otherwise defined, all technical terms and scientific and technical terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention belongs. In case of conflict, the specification (including definitions) will take precedence.
First, the terms and general techniques used in the present invention are explained.

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

In this specification, the term "magnetic particles" refers to particles having magnetism, such as ferromagnetic (Ferromagnetic, Fe, _Ni , _Co , etc.), ferrimagnetic (Ferrimagnetic, _Fe2O3 , _MnFe2O4 , BAO6Fe2O3, _etc. ), paramagnetic (Paramagnetic, Al, Ti, Cu alloy, etc.), and superparamagnetic (Superparamagnetic, _{Fe3O4 , etc.} ), and includes any particles having magnetism, regardless of the degree or type of magnetism _. Sizes can 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, about 10 nm to about 400 nm, and the like.

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

As used herein, "iron-containing metal oxide magnetic particles" refers to _magnetic particles that contain iron oxide (e.g., _Fe2O3 and/or _{Fe3O4 )} .

In this specification, the "circularity" is measured by the formula: circularity=(4πS/L ² ). Here, S is the two-dimensional projected area of the particle, and L is the two-dimensional projected perimeter. To measure the circularity, an electron microscope image is binarized by image processing, and the circularity can be calculated for each particle. The two-dimensional projected area of the particle is obtained by calculating 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 measuring the acquired two-dimensional image of the particle, including notches such as edges. The circularity defined in this disclosure means the average value of the circularity calculated by measuring 500 particles randomly. When the circularity is 1.0, it is a perfect sphere, and the lower the value, the more uneven the outer periphery is, and the higher the degree of irregularity. In magnetic particles having a non-spherical shape, the circularity is preferably 0.6 or less.

In this specification, the "sphericity" is determined by observing a particle in a micrograph and calculating the sum of the circumference and the length of the depression on the particle surface according to the following formula.
Sphericity = (Circumference + Total Length of Indentations on Particle Surface)/Circumference Here, an indentation is determined to exist if (R1-R2)/(R1) is 10% or more, as shown in Figure 1. R1 is the radius of an imaginary outer 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 outer sphere and whose periphery passes through the point closest to the center of the indentation.
The length of the cavity is calculated by R1-R2. When a particle has multiple cavities, the length of the cavities is calculated by adding them together.
The sphericity defined in this disclosure means the average sphericity value obtained by measuring 500 randomly selected particles. A sphericity of 1.0 indicates a perfect sphere, and the larger the value, the more irregular the outer periphery is, and the greater the degree of irregularity.

In this specification, "particle size" refers to the diameter of a particle, and the defined particle size range refers to the range of diameters of each single particle. In this specification, the particle size of magnetic particles is measured from images obtained by 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 a SEM (scanning electron microscope).

As used herein, "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.

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

In this specification, the term "visible material" refers to a material that can be seen with the naked eye and can be colored by adding it. Examples of visible materials include, but are not limited to, dyes and pigments.

In this specification, "ink" refers to a colored liquid or suspension for coloring a substance. It refers to a printing method in which ink is ejected from a jetting basic structure (architecture) such as inkjet architecture and sprayed onto a substance.

In this specification, the term "core" refers to a basic substance that forms a particle. For example, the core may be a metal or a metal oxide, and examples of the metal or metal oxide include iron, ferric oxide, or triiron tetroxide, and preferably ferric oxide. Since the present disclosure may be used in the pharmaceutical field, in this case, the core is preferably a pharma-ceutically acceptable substance, and is preferably a pharma-ceutically acceptable metal or metal oxide.

In this specification, "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.

"Hydrolysis" is used herein to refer to a chemical reaction in which water reacts with a compound to produce another compound, which involves the cleavage of a chemical bond with the addition of hydrogen cations and hydroxide anions from the water. For example, when hydrolyzing iron salts, the progress of the hydrolysis can be monitored by using an iron(III) ion titrant such as EDTA.

In this specification, the term "protective agent" refers to an agent for protecting the nuclei. By using a protective agent, the size growth reaction of the nuclei can be stopped and the nuclei can be stabilized in the solvent. Examples of protective agents include, but are not limited to, sodium acetate, sodium ascorbate, sodium malate, and sodium citrate.

In this specification, the "protective substance" imparted by the "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, and citrate ions.

In this specification, "administration" refers to dispensing an appropriate medication and giving it to a patient, and "taking medication" refers to a patient taking a medication.

As used herein, "magnetic" includes all magnetic, paramagnetic and/or ferromagnetic elements.

In this specification, "sensing means for sensing magnetism" refers to means capable of sensing magnetism and/or changes in a magnetic field. Examples of the sensing means include magnetic sensors, and can be in the form of a necklace, an adhesive sheet (which can be a patch, a tape, etc.), a strap, clothing, underwear, a brassiere, a belt, suspenders, etc.

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., dogs and cats), a livestock animal (e.g., cows, horses, sheep, goats, and pigs), and/or a laboratory animal (e.g., mice, rats, hamsters, guinea pigs, pigs, rabbits, dogs, and monkeys). In some embodiments, the subject (or patient) is a human.

Preferred Embodiments
The preferred embodiments of the present disclosure are 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 a person skilled in the art can make appropriate modifications within the scope of the present disclosure in light of the description in this specification. It is also understood that the following embodiments of the present disclosure can be used alone or in combination.

<Magnetic particles>
In one aspect, the present 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 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, circularity, sphericity, or theoretical surface area ratio (R=Adα/6, where R: surface area ratio, d: D50 particle diameter, α: particle density, and A: BET specific surface area).

In one embodiment, the particle size of the magnetic particles of the present disclosure is 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, or about 10 nm to about 400 nm, preferably 10 nm to 400 nm. It is preferable that the particle size is suitable for use in inkjet.

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.

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, the magnetic responsiveness can be improved, and the magnetic particles can be detected with high sensitivity by the magnetic sensor.

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, the magnetic responsiveness can be improved, and the magnetic particles can be detected with high sensitivity by a magnetic sensor.

<Magnetic particle assembly>
In one aspect, the present disclosure provides a magnetic particle assembly including magnetic particles having a non-spherical shape for use 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>.

In one embodiment, the content of the magnetic particles having a non-spherical shape 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 magnetic particles having a non-spherical shape 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.

<Ink>
In one aspect, the ink of the present disclosure contains the magnetic particles or the 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 <Magnetic particles> and <Magnetic particle aggregates>.

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

In one embodiment, the ink of the present disclosure may further include a solvent, a surfactant, an additive, purified water, etc.

In one embodiment, the ink of the present disclosure contains a visible material, which makes it visible when printed with an inkjet. The inkjet of the present disclosure is selected from the group consisting of dyes, pigments, solvents, surfactants, additives, purified water, etc.

The solvent used in this 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% to 50% by weight, and more preferably 20% to 45% by weight, in the composition. Among these, glycerin or propylene glycol is more preferred as the solvent. This is because these solvents are excellent as humectants and are easily available.

The surfactant used in the present disclosure may include an edible surfactant. The surfactant adjusts the surface tension of the ink composition to an appropriate range, improving the ejection stability of the ink. Examples of surfactants that can be used in the present invention include caffetannin, polyglycerin fatty acid ester, Quillaja saponin, propylene glycol fatty acid ester, lecithin, enzyme-treated lecithin, glycerin fatty acid ester, organic acid monoglyceride, amylose, barium chloride hydrate, sucrose fatty acid ester, sorbitan fatty acid ester, rosemary, sodium pyrophosphate, and the like. 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.

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 in the composition is preferably 0.01% by weight to 0.5% by weight. 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, diacetyl tartaric acid monoglyceride, pectin, tamarind gum, xanthan gum, potassium metaphosphate, carboxymethylcellulose, citric acid, hydroxypropylcellulose, polyvinylpyrrolidone, sodium erythorbate, methylcellulose, and the like. 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.

The water used in this disclosure is preferably water of high purity, such as purified water or ion-exchanged 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.

<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 a nucleus by hydrolyzing a metal salt with water, b) forming a protective substance around the nucleus by adding a protective agent, and c) refluxing the nucleus having the protective agent. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in <Magnetic Particles>.

In one embodiment, the step of hydrolyzing the 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 is capable of forming nuclei.

In one embodiment, the protecting agent can be added by any method, and can usually be added by adding a solution of the protecting agent in a suitable reaction solvent.
Without wishing to be bound by theory, it is believed that upon addition of the protective agent, the protective substance components contained in the protective agent interact with the nucleus and a protective substance is formed around the nucleus, which may be formed via covalent or non-covalent bonds (e.g., ionic bonds, hydrophobic bonds, etc.).

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

In one aspect, the present disclosure provides a method for producing a magnetic particle of the present disclosure, or a magnetic particle assembly of the present disclosure, comprising the steps of:
The method 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') selecting and collecting desired magnetic particles or magnetic particle aggregates as necessary, and e') classifying particles of a desired particle size as necessary. It is understood that the various embodiments described herein can be applied by appropriately combining any of the forms described in <Magnetic Particles>.

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 the formation of nuclei. The conditions that result in the formation of nuclei are typically achieved by mixing the metal salt with a suitable reaction solvent.

In one embodiment, the protective agent can be added in any manner. Without wishing to be bound by theory, it is preferred that the protective agent is added under conditions that result in the formation of a protective substance around the core. The conditions that result in the formation of a protective substance are typically achieved by mixing the protective agent with the core in a suitable reaction solvent.

In one embodiment, refluxing of the cores with the protecting agent can typically be accomplished 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.

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 ... ol ~ 0.04 mol, 0.02 mol ~ 0.03 mol, 0.03 mol ~ 0.1 mol, 0.03 mol ~ 0.09 mol, 0.03 mol ~ 0.08 mol, 0.03 mol~0.07mol, 0.03mol~0.06mol, 0.03mol~0.05mol, 0.03mol~0.04mol, 0.04mol~0.1mol, 0.04 mol ~ 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. 05 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. 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, 0.09 mol to 0.1 mol. The metal salt concentration is preferably 0.04 mol to 0.06 mol. By using a high concentration, the probability of collision between metal salts can be increased, and the probability of forming magnetic particles having a non-spherical shape can be improved.

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, the metal salt is iron chloride, iron bromide, iron perchlorate, or iron hydroxide.

In one embodiment, the hydrolysis in step a) or a') is accomplished 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 0.05 mol, 0.1 mol to 0.06 mol, 0.1 mol to 0.09 mol, 0.1 mol to 0.08 ... ．． 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 ol, 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. By using a high concentration, the probability of collision between metal ions generated by hydrolysis can be increased, and the probability of forming magnetic particles having a non-spherical shape can be improved.

In one embodiment, the hydrolysis in step a) or a') is achieved by heating. The temperature used in 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 temperature is 70°C to 80°C. Heating activates the movement of the material and earns collision energy, which increases the probability of metal ions colliding and improves the probability of forming magnetic particles having a non-spherical shape.

In one embodiment, the protective agent of the present disclosure is sodium acetate, sodium ascorbate, sodium malate, or sodium citrate. The protective agent can be used to control the size growth reaction of the nuclei during nucleation and stabilize them in the solvent. Furthermore, the particles can be made monodisperse, making it possible to produce small particles.

In one embodiment, step b) or b') of the present disclosure includes a step of heating and stirring after adding the protective agent. The temperature at which the mixture is heated 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. The temperature is preferably 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.

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

In one embodiment, step c') of the present disclosure includes a step of heating and stirring before refluxing. The temperature at which the mixture is heated 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, and 90°C to 100°C. It is preferably achieved at 90°C to 100°C. The movement of the substance can be activated and collision energy can be earned, so that the probability of collision of metal ions can be increased, and the probability of forming magnetic particles having a non-spherical shape can be improved.

In one embodiment, step d') of the present disclosure includes collecting the magnetic particles and sorting the desired magnetic particles or magnetic particle aggregates. By sorting the particles, only the more magnetic nanoparticles can be extracted.

<Preparation>
In one aspect, the present disclosure provides a formulation comprising the magnetic particles of the present disclosure, the magnetic particle assembly of the present disclosure, an active ingredient, and, if necessary, an additive. 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 assembly>, and <Ink>. In the present disclosure, the term "active ingredient" is used in the same sense as it is usually used in the art, and refers to any ingredient that is effective in treating or preventing a disease, disorder, or symptom that is the target of treatment or prevention.

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

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.

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

In one embodiment, the information about the formulation of the present disclosure may be the type of formulation (e.g., active ingredient and, if necessary, additives), the dosage, and/or the method of use. It is transmitted by printing an ink containing the magnetic particles or magnetic particle aggregates of the present disclosure on the formulation.

In one embodiment, information about the formulation of the present disclosure, such as the number and dosage, is transmitted by detecting the magnetic information of the magnetic particles. By detecting the magnetic information, it is possible to prevent forgetting to take a dose, taking too much medicine, and taking the wrong medicine, check combinations of medicines (contraindications), check expiration dates (lot numbers), reduce the burden on caregivers, and make remaining medicine management more efficient.

The particles of the present disclosure can be printed on 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. Furthermore, these formulations can be manufactured by known methods, such as by adding additives commonly used as pharmaceutical additives to the active ingredient.

These additives may include excipients, disintegrants, binders, flow agents, lubricants, coating agents, solubilizers, solubilizers, thickeners, dispersants, stabilizers, sweeteners, flavors, etc., depending on the purpose. 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.

In one embodiment, the formulation information of the present disclosure includes visually perceptible information.

(Synthesis Example)
(Method of manufacturing magnetic particles according to the present disclosure)
Specific synthesis examples of the method for producing magnetic particles according to the present disclosure are given in the Examples below, 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.

The magnetic particles of the present disclosure can be produced, for example, by the production methods described below, although they are not limited thereto. These production methods can be appropriately improved based on the knowledge of those skilled in the art.
The iron metal salt 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 solution is refluxed to produce magnetic particles.

(Application)
The magnetic particles, magnetic particle aggregates, inks, and preparations or medication systems printed with magnetic particles of the present disclosure can be used for any purpose, for example, in tablet ink development, detection devices, medication management systems, and the like. The method of the present disclosure provides magnetic particles, magnetic particle aggregates, inks, and preparations or medication systems printed with magnetic particles for these purposes. Preferably, a special material can be printed on the tablet surface by high-speed printing of magnetic nanoparticles using an inkjet, etc., making it possible to sense with a smart necklace or the like, and to identify the tablet type using a sensor. Alternatively, it is a service provided to patients, families, and medical professionals, and individual support can be provided by combined analysis of vital information, and notification of the effects of medication can be made.

Without wishing to be bound by theory, the formulation or medication system disclosed herein may provide unprecedented benefits in terms of safety, cost, and versatility. For example, in vivo safety is guaranteed, and it is dramatically safer than embedding a chip in a tablet. In terms of cost, mass production is easy and inexpensive, 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 are advantageous in that they are different from technologies that have high cost and regulatory hurdles and are difficult to apply to various drugs.

(Example of a medication system)
The system for detecting the taking of medicine according to the present disclosure (sometimes referred to as a medicine taking 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 of medicine by attaching a detection device (e.g., a necklace-type detection device or a patch-type detection device) capable of detecting the magnetic particle aggregate according to the present disclosure to the subject by wearing or attaching it to a part of the subject where the digestive tract of the subject can be detected (e.g., the subject's neck or chest). The information according to the present disclosure can be combined with vital data, activity data, dietary data, sleep data, and the like for each individual subject to provide data on the effect of taking medicine, etc., tailored to the lifestyle of each subject.

<Medication System>
In one aspect, the present disclosure provides a system for detecting ingestion of a drug. Here, the system for detecting ingestion of a drug includes the 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>. The "formulation" described below means the "formulation" of the present disclosure unless otherwise specified.

The detection means of the present disclosure can detect that a subject has taken a formulation, for example, based on the intensity of the sensed magnetism, the distribution (position) of the sensed magnetism, the type of the sensed magnetism, and the manner of printing. For example, it can detect that a subject has taken a formulation when the intensity of the sensed magnetism 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 a disease, etc.).

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

In one embodiment, the system of the present disclosure further includes 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.

The determination means can communicate with the detection means and can receive information from the detection means regarding the subject taking the formulation. The information regarding the subject taking the formulation can include at least one of the fact that the subject has taken the formulation, the amount of the formulation taken by the subject, and information printed on the formulation taken by the subject.

The determination means, for example, identifies the time when the subject took the formulation based on the 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 a predetermined time. For example, if the subject is instructed to take the formulation after waking up, the determination means will determine whether the identified time is between 6:00 and 8:00 a.m. The predetermined time may be, for example, a time window with such a range, or it may be a pinpoint time.

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 a predetermined amount of the formulation. For example, if the subject is instructed to take one tablet of the formulation per dose, the determination means will determine whether the identified amount of the formulation is one tablet.

The determination means can use the information received from the detection means in combination with other sensors (such as sensors that can determine the state of chewing and swallowing, blood glucose level, body temperature, pulse, 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 obtaining the information simultaneously or in parallel with taking the medicine include:
・Breathing, voice, eye movement, excretion, facial expression ・Location information ・Number of steps, walking speed, activity level, food, calorie intake ・Vital data (heart rate, blood pressure, blood glucose level, blood flow, blood oxygen saturation, sleep data, brain waves, weight, body temperature, basal body temperature)
・This includes, but is not limited to, electronic medical record data, health checkup and medical examination data, etc. By combining medication data with the above information, it can be used to visualize the effects of treatment and motivate patients, and to visualize the effects of treatment from the medical and caregiver perspective, as well as for disease management, recurrence prevention, and prognosis management.

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 at a predetermined amount. This is the case when the subject has not taken the formulation as instructed, i.e., when there is poor compliance. Thus, the action at this time can be to encourage the subject to take the medication. For example, the action can be to issue an alarm, and the means for performing the action can be an alarm means. The alarm can be issued visually (e.g., by light), audibly (e.g., by an alarm sound), tactilely (e.g., by vibration), or olfactory (e.g., by 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 medication, and can be sent to the subject's information terminal. The message may be, for example, a message informing the subject that he/she has not taken his/her medication, and may be sent to people in the vicinity of the subject (for example, the subject's family, doctor, nurse, caregiver, etc.). Here, the information terminal may include, but is not limited to, a mobile phone, a smartphone, a tablet, a smart watch, smart glasses, a personal computer, a smart speaker, and a smart TV.

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 is the case when the subject is taking the formulation as instructed, i.e., when compliance is good. Therefore, the action at this time can be for maintaining motivation to take the medication. For example, the action can be sending a message, and 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 information terminal of the subject. The message can be, for example, a message informing the subject that he or she has taken the medication, and can be sent to people around the subject (for example, the subject's family, doctor, nurse, caregiver, etc.). For example, the action can be for storing medication information in association with a treatment effect, and the means for performing the action can be a storage means. For example, a record of taking the medication will be stored in a medication diary or the like.

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 regarding the type of drug, dosage, and/or usage printed thereon using magnetic particles, and the detection means receives a signal from a magnetic sensor to detect the strength of the magnetic field, the distribution (position) of the magnetic field, and the type of the magnetic field.

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

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 with each other via a wire or wirelessly.

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

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

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 the target or a person around the target can communicate with the information processing device via the interface unit.

The interface unit includes, for example, an input unit that enables information to be input to the information processing device. There is no restriction on the manner in which the input unit enables information to be input to the information processing device. For example, if the input unit is a receiver, the receiver may input information by receiving information from outside the information processing device via a network. For example, if the input unit is a data reading device, the information may be input 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.

The interface unit includes, for example, an output unit that enables information to be output from the information processing device. There is no restriction on the manner in which 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 information may be output by the transmitter transmitting the information to the outside of the information processing device via a network.

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 the memory and executes the program. This makes it possible for 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.

The memory stores a program required to execute the processing of the information processing device, data required to execute the program, etc. The memory may store a program for causing the processor unit to execute processing for detecting medication (e.g., a program that realizes the processing shown in FIG. 2). Here, there is no restriction on how the program is stored in the memory. 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.

For example, the above-mentioned detection means and determination means can be implemented by a processor of the information processing device. For example, the above-mentioned means for performing an action can be implemented by a processor of the information processing device, or a processor and an interface unit. Alternatively, the means for performing an action can be implemented by an external device that communicates with the information processing device.

For example, the processor of the above-mentioned information processing device can perform the process shown in FIG.
First, the sensing means receives a signal representing the magnetism of the formulation detected. 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.

In one embodiment, a method for detecting ingestion of the present disclosure, in which the formulation to be ingested includes magnetic particles or magnetic particle aggregates of the present disclosure, or is a formulation of the present disclosure, includes disposing sensing means for sensing the magnetism of the formulation around the subject, sensing the magnetism of the formulation from within the subject with the sensing means, and detecting that the subject has ingested the formulation based on the sensed magnetism.

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 taking 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.

In one embodiment, a program for detecting the ingestion of the present disclosure is provided. Here, the program is executed in a computer system having a processor, and the formulation to be ingested 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 sensing means arranged around the subject, and detecting that the subject has taken the formulation based on the signal representing the magnetism.

In one embodiment, the process of the present disclosure 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.

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

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.

Below, the implementation of this disclosure will be explained using examples, but this disclosure is of course not limited to these. Specific reagents used are those described in the examples, but equivalent products from other manufacturers (Sigma-Aldrich, Wako Pure Chemical Industries, Nakarai, etc.) can be used instead.

(Example 1: Preparation of magnetic particles)
Details are as follows:
(procedure)
FeCl _{3.6H 2} O was dissolved in ethylene glycol. The resulting 0.04 mol _FeCl 3.6H ₂ 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 kept at 70°C and stirred 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 generation of magnetic particles was determined by confirming the change in the color of the solution from brown to black.
The resulting magnetic particles were classified by particle size by methods known in the art.

(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 shown 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 ratio of the raw materials introduced (molar amount: mol. The numbers for iron trichloride, sodium acetate, and distilled water in the table mean mol), and the results are shown in Table 1.

(Example 2: Evaluation of magnetic particles)
An electron microscope image was obtained using a SEM (FIG. 3) of the magnetic particles produced in Example 1. 500 particles were analyzed from the obtained electron microscope image to measure the 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. The magnetic response rate (slope of the calibration curve) (mT/g) was obtained by dividing the obtained magnetic value by the mass of the measured magnetic particles. The magnetic response rate and particle size of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in FIG. 4. The magnetic response rate and sphericity of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in FIG. 5. The magnetic response rate and sphericity of the magnetic particles produced in Example 1 and Comparative Example 1 are summarized in Table 2.

(Example 3: Preparation of ink containing magnetic particles)
The 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.

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

Example 5: Animal Experiments
Dogs or monkeys equipped with a magnetic sensor are used to orally administer the magnetic particle-containing formulation of the present disclosure.
A comparison can then be made between the placebo and the magnetic particle-containing formulation to assess the drug administration of the magnetic particle-containing formulation of the present disclosure as it passes through the dog or monkey body.

Example 6: Human Application: Dosage Examples
The 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 taking the formulation. If the type of formulation taken, the amount of formulation taken, and the timing of taking the formulation can be measured, the method can be widely used in a medication management system.
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 taking medication in accordance with lifestyle.

(Note)
As described above, the present disclosure has been illustrated using preferred embodiments of the present disclosure, but it is understood that the scope of the present disclosure should be interpreted only by the scope of the claims. It is understood that the patents, patent applications and other documents cited in this specification should be incorporated by reference to this specification in the same manner as if the contents themselves were specifically described in this specification. 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.

The technology provided in this disclosure can be used in any field that utilizes technology to observe magnetism within the body.

Claims (37)

Magnetic particles with a non-spherical shape. 2. The magnetic particles according to claim 1, wherein the magnetic particles have a magnetic response rate/particle size of 0.5×10 ⁻³ μT/(mg·nm) or more. The magnetic particles according to claim 1 or 2, wherein the particle size of the magnetic particles is 10 nm to 500 nm. 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. 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. A magnetic particle aggregate including magnetic particles having a non-spherical shape. The magnetic particle aggregate according to claim 6, wherein the magnetic particles having a non-spherical shape are as described in any one of claims 2 to 5. The magnetic particle assembly according to claim 6 or 7, wherein the content of the non-spherical magnetic particles is 40% or more of the total magnetic particles. The magnetic particle assembly 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. A composition comprising the magnetic particle aggregate according to any one of claims 6 to 9, wherein the content of the magnetic particles having a non-spherical shape is 50% or more relative to the composition. A magnetic particle-containing ink containing the magnetic particles described in any one of claims 1 to 5, or the magnetic particle aggregate described in any one of claims 6 to 10. 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. The magnetic particle-containing ink according to claim 11 or 12, further comprising a dye or pigment. 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. 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 nuclei by hydrolyzing a metal salt with water;
b) adding a protective agent to form a protective agent around the core;
and c) refluxing the cores with said protecting agent. 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 method 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') optionally selecting and collecting desired magnetic particles or magnetic particle aggregates; and e') optionally classifying particles of a desired particle size. The method according to claim 15 or 16, wherein the concentration of the metal salt is 0.04 mol to 0.06 mol. The method according to any one of claims 15 to 17, wherein the metal salt comprises iron chloride, iron bromide, iron perchlorate or iron hydroxide. The method of claim 15 or 16, wherein the hydrolysis is accomplished by adding water. The method of claim 15 or 16, wherein the protective agent comprises sodium acetate, sodium ascorbate, sodium malate or sodium citrate. The method according to claim 15 or 16, wherein the portion of the protective agent applied to the nucleus is an acetate ion, an ascorbate ion, a malate ion, or a citrate ion. The method according to claim 15 or 16, wherein step c') includes a step of stirring at 90°C to 100°C before the refluxing. 　Magnetic particles or magnetic particle aggregates produced by the method according to any one of claims 15 to 22. A formulation comprising the magnetic particles 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, if necessary, 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. The formulation of claim 24 or 25, wherein the magnetic particles or magnetic particle aggregates are contained in the formulation in an inkjet printed form. 1. A system for detecting medication ingestion, 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 magnetism. The system of claim 27, wherein the detection means detects the amount of the formulation administered to the subject based on the sensed magnetism. 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;
30. The system of claim 28, further comprising: means for taking an action in response to a result of the determination by the means for determining. 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;
30. The system of claim 29, wherein the action includes at least one of raising an alarm and sending a message. 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 system of claim 30, wherein the action includes at least one of sending a message and storing medication information in association with a therapeutic effect. The formulation has information printed thereon by the magnetic particles,
A system according to any one of claims 27 to 31, wherein the detection means detects the information based on the sensed magnetism. A method for detecting ingestion of a drug, the drug formulation to be ingested 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 the drug formulation according to any one of claims 24 to 26, the method comprising the steps of:
placing a sensing means for sensing the magnetic field of the formulation around the subject;
sensing the magnetic field of the formulation from within the subject with the sensing means;
and detecting that the subject has ingested the formulation based on the sensed magnetism. 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;
34. The method of claim 33, comprising taking 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. A program for detecting ingestion of a drug, the program being executed in a computer system having a processor, the drug formulation to be ingested comprising the magnetic particles according to any one of claims 1 to 5 or the magnetic particle assembly according to any one of claims 6 to 9, or the drug formulation according to any one of claims 24 to 26, the program comprising:
receiving a signal representative of the magnetic properties of the formulation as sensed by sensing means disposed about the subject;
and detecting that the subject has taken the formulation based on a signal representing the magnetism. The process comprises:
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;
36. The method of claim 35, further comprising: performing an action in response to said determining. The magnetic particles contained in the preparation are printed on the preparation, and information is imparted to the magnetic particles by the printing.
The program of claim 35 or 36, wherein information printed on the formulation is also utilized in the determination.