Digestive function measurement device, digestive function measurement system, and digestive function measurement method

Abstract

The function of digestive fluids is evaluated non-invasively. [Solution] A digestive function measuring device according to one embodiment measures the digestive function of digestive fluid. This digestive function measuring device comprises a measuring unit including a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles placed in the digestive fluid, a receiving unit that detects a magnetic signal including a magnetization response signal that shows the magnetization response of one or more magnetic particles to the external magnetic field, and an analysis unit that acquires parameters indicating the digestive function of the digestive fluid based on the magnetic signal received by the receiving unit.

Description

Technical Field

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[0001] The present disclosure relates to a digestive function measuring device, a digestive function measuring system, and a digestive function measuring method.

Background Art

[0002] Measuring the function of digestive juices is important for evaluating the function of the entire digestive system. There are extremely few non-invasive methods for evaluating the function of digestive juices. For example, as a technique for evaluating the function of the digestive system, X-ray computed tomography (CT) that images the inside of a living body using X-rays is known. In addition, as other techniques for imaging the inside of a living body, imaging techniques using magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) are known (for example, Patent Document 1 and Patent Document 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] X-ray CT technology has problems with the safety of continuous monitoring due to the influence of radiation exposure. Although the techniques described in Patent Documents 1 and 2 can image the digestive system, it is not easy to evaluate the function of digestive juices from the images of the digestive system.

[0005] Therefore, an object of the present disclosure is to non-invasively evaluate the function of digestive juices. <0​​​​​A digestive function measuring device according to one embodiment measures the digestive function of digestive fluid. This digestive function measuring device comprises a measuring unit including a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles placed in the digestive fluid, a receiving unit that detects a magnetic signal including a magnetization response signal that shows the magnetization response of one or more magnetic particles to the external magnetic field, and an analysis unit that acquires parameters indicating the digestive function of the digestive fluid based on the magnetic signal received by the receiving unit.

[0007] In the digestive function measuring device according to this embodiment, an external magnetic field is applied to magnetic particles placed in digestive fluid, and a magnetic signal including the magnetization response signal of the magnetic particles is acquired. Since the magnetization response of the magnetic particles changes according to the degree of digestion of the magnetic particles by the digestive fluid, this digestive function measuring device allows for the non-invasive measurement of the digestive function of the digestive fluid based on the magnetic signal.

[0008] A digestive function measuring device according to one embodiment further comprises a reference unit including a magnetic field generating unit that applies an external magnetic field to one or more reference magnetic particles placed outside the digestive fluid, a receiving unit that detects a reference signal including a magnetization response signal showing the magnetization response of one or more reference magnetic particles to the external magnetic field, and a processing unit that acquires a difference signal showing the difference between the magnetic signal and the reference signal, and an analysis unit that acquires parameters showing the digestive function of the digestive fluid based on the difference signal. In this embodiment, by using a difference signal showing the difference between the magnetic signal and the reference signal, noise components in the magnetic signal caused by unwanted radiation can be removed. Therefore, the measurement accuracy of the digestive function of the digestive fluid can be improved.

[0009] In one embodiment, the analysis unit may obtain parameters indicating the digestive function of the digestive fluid based on the signal intensity in each frequency domain obtained by performing a Fourier transform of the difference signal with respect to the time variable. By using the signal intensity in each frequency domain, the digestive function of the digestive fluid can be measured with high accuracy.

[0010] In one embodiment, the analysis unit may obtain parameters indicating the digestive function of the digestive fluid based on the phases of each frequency domain obtained by performing a Fourier transform of the difference signal with respect to the time variable. By using the phases of each frequency domain, the digestive function of the digestive fluid can be measured with high accuracy.

[0011] A digestive function measuring device according to one embodiment further includes a storage unit that stores difference signals observed when an external magnetic field is applied to one or more magnetic particles placed in another digestive fluid having known digestive function, and parameters indicating the digestive function of the digestive fluid may be obtained based on the correlation between the difference signals obtained by the processing unit and the difference signals stored in the storage unit. In this case, the digestive function of the digestive fluid can be measured with high accuracy.

[0012] In one embodiment, the analysis unit may acquire information indicating the acidity of the digestive fluid based on the magnetic signal. In this embodiment, the acidity of the digestive fluid, which is a useful indicator for evaluating the function of the digestive fluid, can be acquired.

[0013] In one embodiment, the analysis unit may acquire information indicating the particle size of one or more magnetic particles as a parameter indicating the digestive function of the digestive fluid. In this embodiment, the function of the digestive fluid can be evaluated from the particle size of the magnetic particles, which changes over time according to the stage of digestion.

[0014] A digestive function measuring device according to one embodiment further comprises a reference unit including a magnetic field generating unit that applies an external magnetic field to one or more reference magnetic particles placed in another digestive fluid, and a receiving unit that detects a reference signal including a magnetization response signal showing the magnetization response of one or more reference magnetic particles to the external magnetic field, a function adjustment unit that adjusts the digestive function of another digestive fluid, and a processing unit that acquires a difference signal showing the difference between a magnetic signal and a reference signal, wherein the analysis unit may identify the digestive function of another digestive fluid that minimizes the difference signal while changing the digestive function of the other digestive fluid by the function adjustment unit, and determine the identified digestive function of the other digestive fluid as the digestive function of the digestive fluid.

[0015] A digestive function measuring device according to one embodiment may include a drive unit for moving a measuring unit and an image generation unit for generating an intensity distribution image showing the distribution of signal intensity of the magnetic signal detected by the measuring unit at each position. The distribution of signal intensity of the magnetic signal corresponds to the distribution of magnetic particles. Therefore, the distribution of magnetic particles can be visually recognized from the intensity distribution image.

[0016] In one embodiment, the image generation unit periodically generates intensity distribution images to create a plurality of intensity distribution images arranged in a time series, and the digestive function measuring device may include an image analysis unit that analyzes the plurality of intensity distribution images to identify the position of one or more magnetic particles at each time point, and acquires the movement velocity of the magnetic particles based on the position of one or more magnetic particles at each time point. In this embodiment, the movement velocity of the magnetic particles, which is a useful indicator for evaluating the function of the entire digestive system, can be acquired.

[0017] In one embodiment, the magnetic particles include a plurality of magnetic particles supported on a transport carrier, and the image analysis unit may analyze a plurality of intensity distribution images to obtain information indicating the time required from administration to disintegration of the transport carrier, the disintegration location of the transport carrier, and the amount of magnetic particles released. By understanding the time required from administration to disintegration of the transport carrier, the disintegration location of the transport carrier, and the amount of magnetic particles released, it becomes possible to accurately deliver the drug to the target site, thereby contributing to an improvement in the accuracy of drug delivery.

[0018] In one embodiment, the magnetic particles include a plurality of magnetic particles supported on a transport carrier, the image generation unit periodically generates intensity distribution images to generate a plurality of intensity distribution images arranged in a time series, and the digestive function measuring device may include an image analysis unit that analyzes the plurality of intensity distribution images to identify the distribution of the plurality of magnetic particles at each time point and acquires information indicating the inner diameter of the digestive tract based on the distribution of the plurality of magnetic particles at each time point.

[0019] In one embodiment, the receiving unit may include an induction coil, a Hall sensor, a magnetoresistive element, an optical pumping magnetometer, or a superconducting quantum interferometer.

[0020] In one embodiment, the analysis unit may acquire parameters indicating the digestive function of the digestive fluid using time-domain analysis, frequency-domain analysis, harmonic analysis, phase analysis, intermodulation, or interference measurement of the magnetic signal.

[0021] A digestive function measurement system according to one embodiment measures the digestive function of digestive fluid. This digestive function measurement system comprises a measurement unit including one or more magnetic particles placed in the digestive fluid, a magnetic field generating unit that applies an external magnetic field to the one or more magnetic particles whose magnetic field strength changes over time, and a receiving unit that detects a magnetic signal including a magnetization response signal showing the magnetization response of one or more magnetic particles to the external magnetic field, and an analysis unit that acquires parameters indicating the digestive function of the digestive fluid based on the magnetic signal received by the receiving unit.

[0022] In the digestive function measurement system according to this embodiment, an external magnetic field is applied to magnetic particles placed in digestive fluid, and a magnetic signal including the magnetization response signal of the magnetic particles is acquired. Since the magnetization response of the magnetic particles changes according to the degree of digestion of the magnetic particles by the digestive fluid, this digestive function measurement device can non-invasively measure the digestive function of the digestive fluid based on the magnetic signal.

[0023] In one embodiment, the magnetic particles comprise a plurality of magnetic particles, and the digestive function measurement system further comprises a crosslinking agent that is digestible by digestive fluid and binds the plurality of magnetic particles together to form aggregates. The analysis unit may acquire parameters indicating the digestive function of the digestive fluid based on a magnetic signal that changes according to the degree of dispersion of the plurality of magnetic particles due to the digestion of the crosslinking agent. Since the magnetization response of the magnetic particles changes according to the degree of dispersion of the plurality of magnetic particles, the analysis unit can evaluate the digestive function of the digestive fluid based on a magnetic signal that changes according to the degree of dispersion of the magnetic particles due to the digestion of the crosslinking agent.

[0024] In one aspect, the one or more magnetic particles include a plurality of magnetic particles, the plurality of magnetic particles are coated with a hydrophilic agent that is digested by a digestive fluid, and the analysis unit may obtain a parameter indicating the digestive function of the digestive fluid based on a magnetic signal that changes according to the degree of condensation of the magnetic particles due to the digestion of the hydrophilic agent. When the hydrophilic agent is digested by the digestive fluid, the hydrophobic magnetic particles gather and aggregate together. Since the magnetization response of the magnetic particles changes according to the degree of aggregation of the plurality of magnetic particles, the analysis unit can evaluate the digestive function of the digestive fluid based on the magnetic signal that changes according to the degree of aggregation of the magnetic particles due to the digestion of the cross-linking agent.

[0025] A method for measuring a digestive function according to one aspect includes applying an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles disposed in a digestive fluid, detecting a magnetic signal including a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field, and obtaining a parameter indicating the digestive function of the digestive fluid based on the change over time of the magnetic signal.

Advantages of the Invention

[0026] According to the present disclosure, the function of the digestive fluid can be evaluated non-invasively.

Brief Description of the Drawings

[0027] [Figure 1] It is a diagram schematically showing a digestive function measurement system according to one embodiment. [Figure 2] It is a diagram showing a plurality of magnetic particles supported on a carrier. [Figure 3] (a) to (c) are diagrams showing the relationship between the particle size of magnetic particles and the magnetization curve of the magnetic particles. [Figure 4] (a) to (c) are diagrams showing examples of the frequency spectrum of a reference signal, (d) to (f) are diagrams showing examples of the frequency spectrum of a magnetic signal, and (g) to (i) are diagrams showing examples of the frequency spectrum of a differential signal. [Figure 5] It is a diagram showing a plurality of magnetic particles bonded with a cross-linking agent. [Figure 6](a) shows magnetic particles in an aggregated state and their magnetization curve, and (b) shows magnetic particles in a dispersed state and their magnetization curve. [Figure 7] (a) shows an example of the frequency spectrum of aggregated magnetic particles, (b) shows an example of the frequency spectrum of dispersed magnetic particles, (c) shows an example of the phase spectrum of aggregated magnetic particles, and (d) shows an example of the phase spectrum of dispersed magnetic particles. [Figure 8] (a) and (b) are diagrams showing multiple magnetic particles dispersed by a hydrophilic agent. [Figure 9] (a) shows magnetic particles in a dispersed state and their magnetization curve, and (b) shows magnetic particles in an aggregated state and their magnetization curve. [Figure 10] (a) shows an example of the frequency spectrum of dispersed magnetic particles, (b) shows an example of the frequency spectrum of aggregated magnetic particles, (c) shows an example of the phase spectrum of dispersed magnetic particles, and (d) shows an example of the phase spectrum of aggregated magnetic particles. [Figure 11] This figure schematically shows a digestive function measurement system according to another embodiment. [Figure 12] (a) is a diagram showing an example of the waveform of a reference signal, (b) is a diagram showing an example of the waveform of a magnetic signal, and (c) is a diagram showing an example of the waveform of a difference signal, which shows the difference between the reference signal shown in (a) and the magnetic signal shown in (b). [Figure 13] This is a schematic diagram illustrating a digestive function measurement system according to yet another embodiment. [Figure 14] This is a schematic diagram showing the measurement unit. [Figure 15] This figure shows an example of an intensity distribution image. [Figure 16] This figure shows the trajectory of magnetic particles. [Figure 17] Figures (a) to (c) show the intensity distribution images at time t1, time t2, and time t3, respectively. [Figure 18] This figure shows a gel containing multiple magnetic particles. [Figure 19]Figures (a) to (d) show examples of intensity distribution images. [Figure 20] A flowchart showing a method for measuring digestive function according to one embodiment. [Figure 21] This flowchart shows a method for measuring digestive function according to another embodiment. [Modes for carrying out the invention]

[0028] Embodiments of the present disclosure will be described below with reference to the drawings. In the following description, the same or equivalent elements will be denoted by the same reference numerals, and redundant descriptions will not be repeated.

[0029] Figure 1 is a schematic diagram of a digestive function measurement system 1 according to one embodiment. The digestive function measurement system 1 shown in Figure 1 non-invasively evaluates the function of digestive fluids using magnetic particles S1. Digestive fluids are liquids containing digestive enzymes secreted from the digestive organs, such as saliva, gastric juice, pancreatic juice, bile, or intestinal juice. The function of digestive fluids refers to the digestive capacity, decomposition capacity, or activity of digestive enzymes of the digestive fluids. Parameters indicating the digestive capacity of digestive fluids include, for example, the acidity of the digestive fluid, the digestion rate, and the amount of digestive enzymes.

[0030] Magnetic particles S1 are particles that have the property of becoming magnetized in response to an external magnetic field. Magnetic particles S are, for example, metallic magnetic particles. As magnetic particles S1, for example, iron oxide (Fe3O4) with nanoscale particle size is used. Note that magnetic particles S1 may also contain magnetic particles other than iron, such as nickel or cobalt. The following describes the case where the digestive fluid is stomach acid capable of digesting magnetic particles S1.

[0031] The magnetization properties of magnetic particles S1 change depending on factors such as particle size, composition, temperature, external magnetic field strength, and interparticle interactions. For example, Figures 3(a) to 3(c) show the relationship between the particle size of magnetic particles S1 and the magnetization curve of magnetic particles S1. Figure 3(a) shows magnetic particles S1 in their initial state (before digestion) and their magnetization curve, and Figure 3(b) shows magnetic particles S1 and their magnetization curve in a state where the particle size has decreased due to digestion (during digestion). Figure 3(c) shows magnetic particles S1 and their magnetization curve in a state where they have been completely digested (after digestion). As shown in Figure 3(a), magnetic particles S1 before digestion have a nonlinear magnetization curve. In contrast, as shown in Figures 3(b) and 3(c), as the particle size of magnetic particles S1 decreases due to digestion, the magnetization curve of magnetic particles S1 gradually approaches linearity. The digestion function measurement system 1 measures the function of the digestive fluid based on the magnetization properties of magnetic particles S1 that change according to the progress of digestion.

[0032] As shown in Figure 1, the digestive function measurement system 1 comprises one or more magnetic particles S1, one or more reference magnetic particles S0, and a digestive function measurement device 2. The magnetic particles S1 are placed in the measurement area MR. The measurement area MR is a region within the digestive fluid 4. That is, the magnetic particles S1 are placed within the digestive fluid 4. The digestive fluid 4 is, for example, gastric juice capable of digesting the magnetic particles S1. As shown in Figure 2, the multiple magnetic particles S1 are orally administered to the subject while being carried on a transport carrier 70. The transport carrier 70 is, for example, a capsule, tablet, gel carrier, etc. The transport carrier 70 may also contain a drug along with the multiple magnetic particles S1.

[0033] A digestive function measuring device 2 according to one embodiment comprises a measuring unit 10, a reference unit 20, a processing unit 30, an analysis unit 40, and a storage unit 50. The measuring unit 10 includes a magnetic field generating unit 11 and a receiving unit 12. The magnetic field generating unit 11 applies an external magnetic field H(t) to the measurement area MR. The measurement area MR is a region within the digestive fluid 4, and magnetic particles S1 are placed in the measurement area MR. The magnetic field generating unit 11 includes an AC power supply 13, an excitation coil 14, and a phase modulator 15.

[0034] The AC power supply 13 supplies voltage to the excitation coil 14. For example, the AC power supply 13 generates an AC voltage having a frequency of 0.1 kHz to 300 kHz. The excitation coil 14 generates an external magnetic field H(t) with the supplied AC voltage and applies this external magnetic field H(t) to the measurement region MR. The magnetic field strength of the external magnetic field H(t) changes over time according to time t. For example, the external magnetic field H(t) is an AC magnetic field whose magnetic field strength changes periodically. The external magnetic field H(t) generated by the excitation coil 14 has, for example, a magnetic field strength (RMS value) of 1 kA / m to 30 kA / m and a frequency of 0.1 kHz to 300 kHz. The external magnetic field H(t) may also be a pulsed magnetic field having a pulsed waveform. The magnetic field generation unit 11 may be equipped with a magnetic transducer or magnetic antenna, etc., instead of the excitation coil 14, as long as it can generate the external magnetic field H(t).

[0035] The phase modulator 15 adjusts the phase of the AC voltage supplied to the excitation coil 14. This controls the phase of the external magnetic field H(t) generated by the excitation coil 14. The phase modulator 15 is composed of an LC circuit, for example, a combination of an inductor and a capacitor.

[0036] The receiving unit 12 includes a receiving coil 16 and a phase modulator 17. The receiving coil 16 is an induction coil that detects a magnetic signal MS1 which includes a magnetization response signal indicating the magnetization response of a magnetic particle S1 to an external magnetic field H(t). When an external magnetic field H(t) is applied to the measurement region MR from the excitation coil 14, the magnetization of the magnetic particle S1 placed in the measurement region MR changes. This change in magnetization depends on the characteristics of the magnetic particle S1 (e.g., particle size, composition, temperature, strength of the external magnetic field, interparticle interaction, etc.). The change in magnetization of the magnetic particle S1 (magnetization response) affects the surrounding magnetic field. The receiving coil 16 generates an induced electromotive force corresponding to the magnetization response of the magnetic particle S1 and outputs this induced electromotive force as a magnetic signal MS1. The magnetic signal MS1 is a time-changing signal which includes the magnetization response signal. The magnetization response signal is a signal which indicates the change in the magnetic signal MS1 associated with the magnetization response of the magnetic particle S1. Furthermore, if the receiving unit 12 can detect the magnetic signal MS1, it may have a Hall sensor, a magnetoresistive element, an optical pumping magnetometer, or a superconducting quantum interferometer instead of the receiving coil 16.

[0037] The phase modulator 17 adjusts the phase of the magnetic signal MS1 output from the receiving coil 16. The phase modulator 17 is composed of an LC circuit, for example, a combination of an inductor and a capacitor.

[0038] The reference unit 20 is a device for generating a reference signal MS2 and has substantially the same configuration as the measurement unit 10. Specifically, the reference unit 20 includes a magnetic field generator 21 and a receiving unit 22. The magnetic field generator 21 applies an external magnetic field to the reference region RR. The reference region RR is a region outside the digested fluid 4. Reference magnetic particles S0 are placed in the reference region RR. The reference magnetic particles S0 are magnetic materials having the same material and particle size as the magnetic particles S1. As described above, the magnetic particles S1 are exposed to the digested fluid 4, whereas the reference magnetic particles S0 are not exposed to the digested fluid 4.

[0039] The magnetic field generator 21 includes an AC power supply 23, an excitation coil 24, and a phase modulator 25. The AC power supply 23 supplies an AC voltage to the excitation coil 24. For example, the AC power supply 23 generates an AC voltage having a frequency of 0.1 kHz to 300 kHz. The excitation coil 24 generates an external magnetic field H(t) with the supplied AC voltage and applies this external magnetic field to the reference region RR. The magnetic field strength of the external magnetic field H(t) changes over time according to time t. The external magnetic field H(t) generated by the excitation coil 24 is substantially the same as the external magnetic field generated by the excitation coil 14. That is, the external magnetic field H(t) has, for example, a magnetic field strength (RMS value) of 1 kA / m to 30 kA / m and a frequency of 0.1 kHz to 300 kHz. Note that the external magnetic field H(t) may be a pulsed magnetic field having a pulsed waveform in terms of magnetic field strength. The magnetic field generating unit 21 may be equipped with a magnetic transducer or magnetic antenna, etc., instead of the excitation coil 24, as long as it can generate an external magnetic field H(t).

[0040] The phase modulator 25 adjusts the phase of the AC voltage supplied to the excitation coil 24. This controls the phase of the external magnetic field generated by the excitation coil 24. The phase modulator 25 is composed of an LC circuit, for example, a combination of an inductor and a capacitor.

[0041] The receiving unit 22 includes a receiving coil 26 and a phase modulator 27. The receiving coil 26 is an induction coil that detects a reference signal MS2 which includes a magnetization response signal that shows the magnetization response of a reference magnetic particle S0 to an external magnetic field H(t). The receiving coil 16 generates an induced electromotive force corresponding to the magnetization response of the reference magnetic particle S0 and outputs this induced electromotive force as the reference signal MS2. The reference signal MS2 is a time-changing signal which includes the magnetization response signal of the reference magnetic particle S0 that is not affected by digestion by the digestive fluid 4. The magnetization response signal is a signal that shows the change in the reference signal MS2 due to the magnetization response of the reference magnetic particle S0. The receiving unit 12 may have a Hall sensor, a magnetoresistive element, an optical pumping magnetometer, or a superconducting quantum interferometer instead of the receiving coil 16, as long as it can detect the reference signal MS2.

[0042] The phase modulator 27 adjusts the phase of the reference signal MS2 output from the receiving coil 26 so that the phase of the magnetic signal MS1 output from the receiving coil 16 matches the phase of the reference signal MS2 output from the receiving coil 26. The phase modulator 27 is composed of, for example, an LC circuit combining an inductor and a capacitor.

[0043] The processing unit 30 is a circuit that receives magnetic signal MS1 and reference signal MS2 from the measurement unit 10 and reference unit 20, and calculates the difference between the two signals. As shown in Figure 1, the processing unit 30 includes a filter 31, an operational amplifier 32, and an AD converter 33. The filter 31 receives magnetic signal MS1 and reference signal MS2 from the measurement unit 10 and reference unit 20, and removes noise components from magnetic signal MS1 and reference signal MS2. For example, filter 31 is a low-pass filter that removes high-frequency components from magnetic signal MS1 and reference signal MS2.

[0044] The operational amplifier 32 receives the magnetic signal MS1 and the reference signal MS2 from the filter 31, from which noise components have been removed, and outputs a difference signal DS that shows the difference between the magnetic signal MS1 and the reference signal MS2. For example, the operational amplifier 32 inverts the phase of one of the signals, the magnetic signal MS1 or the reference signal MS2, and combines the two signals. As described above, the magnetic signal MS1 includes the magnetization response signal and the external magnetic field H(t), but the component of the magnetization response signal is very small compared to the component of the external magnetic field H(t). That is, the component of the external magnetic field H(t) becomes unwanted radiation interference. The difference signal DS is the signal obtained by removing unwanted radiation components other than the magnetization response signal from the magnetic signal MS1. That is, the difference signal DS contains a magnetization response signal with a high signal-to-noise ratio. The difference signal DS changes over time according to time t.

[0045] The AD converter 33 samples the difference signal DS output from the operational amplifier 32 at a predetermined sampling frequency and converts the difference signal DS into digital data.

[0046] The analysis unit 40 is, for example, a computing device including a processor, and acquires parameters indicating the digestive function of the digestive fluid 4 based on the time-dependent changes in the difference signal DS output from the AD converter 33. As described above, since the difference signal DS is generated using the magnetic signal MS1, it can also be said that the analysis unit 40 acquires parameters indicating the digestive function of the digestive fluid 4 based on the magnetic signal MS1, which includes the magnetic response signal. For example, the analysis unit 40 analyzes the signal intensity in each frequency domain obtained by performing a Fourier transform on the difference signal DS with respect to the time variable. The Fourier transform is, for example, the Fast Fourier Transform or the Discrete Fourier Transform.

[0047] Figures 4(a) to 4(c) show examples of frequency spectra obtained by Fourier transforming the reference signal MS2. Figure 4(d) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to the magnetic particle S1 before digestion. Figure 4(e) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to the magnetic particle S1 during digestion. Figure 4(f) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to the magnetic particle S1 after digestion. Note that the frequency spectra shown in Figures 4(d) to 4(f) are shown with the signal intensity inverted.

[0048] Figure 4(g) shows the frequency spectrum of the difference signal DS, which represents the difference between the frequency spectrum of the reference signal MS2 shown in Figure 4(a) and the frequency spectrum of the magnetic signal MS1 shown in Figure 4(d). Figure 4(h) shows the frequency spectrum of the difference signal DS, which represents the difference between the frequency spectrum of the reference signal MS2 shown in Figure 4(b) and the frequency spectrum of the magnetic signal MS1 shown in Figure 4(e). Figure 4(i) shows the frequency spectrum of the difference signal DS, which represents the difference between the frequency spectrum of the reference signal MS2 shown in Figure 4(c) and the frequency spectrum of the magnetic signal MS1 shown in Figure 4(f). In practice, the analysis unit 40 may generate only the frequency spectrum of the difference signal DS without generating the frequency spectrum of the reference signal MS2 for the magnetic signal MS1.

[0049] As shown in Figures 4(d) to (f), the signal intensity of the frequency spectrum of the magnetic signal MS1 before digestion is high, and as digestion progresses, the signal intensity gradually decreases. Finally, after digestion, the signal intensity decreases further, and the signal intensity of the frequency spectrum of the magnetic signal MS1 approaches zero. As a result, as shown in Figures 4(g) to (i), as digestion progresses, the signal intensity in each frequency range of the frequency spectrum of the difference signal DS increases. Therefore, the degree of digestion of the magnetic particles S1 (e.g., the particle size of the magnetic particles S1) can be evaluated through the change in the frequency spectrum of the difference signal DS.

[0050] For example, the memory unit 50 stores the frequency spectrum of the difference signal DS observed when an external magnetic field H(t) is applied to a magnetic particle S1 of a known degree of digestion (e.g., a known particle size). The analysis unit 40 determines the degree of digestion of the magnetic particle S1 based on the correlation between the frequency spectrum of the difference signal DS output from the processing unit 30 and the frequency spectrum stored in the memory unit 50. For example, the analysis unit 40 identifies a frequency spectrum from among the multiple frequency spectra stored in the memory unit 50 that has the spectral pattern closest to the frequency spectrum of the difference signal DS, and determines the particle size associated with the identified frequency spectrum as the particle size of the magnetic particle S1. The particle size of the magnetic particle S1 is an indicator of the degree of digestion of the magnetic particle S1.

[0051] The analysis unit 40 may determine the degree of digestion of the magnetic particles S1 using the average value of the signal intensity in each frequency region of the frequency spectrum, or it may determine the degree of digestion of the magnetic particles S1 using the signal intensity in a specific frequency region of the frequency spectrum.

[0052] The analysis unit 40 may acquire the degree of digestion of the magnetic particles S1 over time and obtain other parameters indicating the function of the digesting fluid 4 from the time-series change in the degree of digestion of the magnetic particles S1. For example, the analysis unit 40 may acquire information indicating the digestion rate of the magnetic particles S1 by the digesting fluid 4 based on the time from the start to the end of digestion. The analysis unit 40 may also acquire the acidity of the digesting fluid 4 from the time-series change in the particle size of the magnetic particles S1. For example, the analysis unit 40 evaluates that the acidity of the digesting fluid 4 is higher the larger the rate of change per unit time of the particle size of the magnetic particles S1.

[0053] The analysis unit 40 outputs parameters indicating the digestive function of the acquired digestive fluid 4. For example, the digestive function measuring device 2 may display information indicating the acquired parameters on a display device, or it may transmit information indicating the acquired parameters to another device via a network.

[0054] As described above, in the digestive function measuring device 2 according to one embodiment, an external magnetic field H(t) is applied to magnetic particles S1 placed in the digestive fluid 4, and a magnetic signal MS1 including a magnetization response signal is acquired. By utilizing the fact that the magnetization response of the magnetic particles S1 changes according to the degree of digestion of the magnetic particles S1 by the digestive fluid 4, the digestive function measuring device 2 can non-invasively measure the digestive function of the digestive fluid 4 based on the change in the magnetic signal MS1 over time. In particular, iron oxide is a substance that is highly safe for living organisms and can be used in food. Therefore, this digestive function measuring device 2 can measure the function of the digestive fluid 4 with high biocompatibility.

[0055] Furthermore, the digestive function measuring device 2 can remove noise components in the magnetic signal MS1 caused by unwanted radiation by using a difference signal DS that shows the difference between the magnetic signal MS1 and the reference signal MS2. Therefore, the digestive function of the digestive fluid 4 can be measured with high accuracy. If the noise components of the magnetic signal MS1 can be removed, the digestive function of the digestive fluid 4 may be measured based on the change in the magnetic signal MS1 over time without using the difference signal DS.

[0056] In the above-described embodiment, parameters indicating the digestive function of the digestive fluid 4 are obtained based on the signal intensity of the magnetic signal MS1, which changes according to the degree of digestion of the magnetic particles S1. However, in one embodiment, parameters indicating the digestive function of the digestive fluid 4 may be obtained based on the signal intensity of the magnetic signal MS1, which changes due to interparticle interactions. This method is mainly useful for measuring the function of digestive fluids 4 that do not digest the magnetic particles S1, such as pancreatic juice, bile, and intestinal juice. Below, an embodiment in which parameters indicating the digestive function of the digestive fluid 4 are obtained using interparticle interactions will be described.

[0057] The digestive function measurement system 1 according to this embodiment includes a crosslinking agent 72. As shown in Figures 5(a) and 5(b), the crosslinking agent 72 binds a plurality of magnetic particles S1 to form aggregates of the plurality of magnetic particles S1. The crosslinking agent 72 is, for example, a crosslinked linker or crosslinked polymer that can be digested by the digestive fluid 4. As a digestible crosslinked linker, for example, a peptide is used. As a digestible crosslinked polymer, for example, crosslinked casein is used. Before the digestion of the crosslinking agent 72, the plurality of magnetic particles S1 are bound to each other. The state in which the plurality of magnetic particles S1 are bound to each other is called the aggregated state. When the crosslinking agent 72 is digested by the digestive fluid 4, the binding of the plurality of magnetic particles S1 is released, and they become dispersed. In order to promote the dispersion of the plurality of magnetic particles S1, each of the plurality of magnetic particles S1 may be coated with a hydrophilic agent that is not digested by the digestive fluid 4.

[0058] The magnetization properties of multiple magnetic particles S1 depend on inter-particle interactions. In this embodiment, the function of the digestive fluid 4 is measured based on the magnetization properties of the magnetic particles S1 that change due to inter-particle interactions. For example, Figure 6(a) shows magnetic particles S1 in an aggregated state and their magnetization curve, and Figure 6(b) shows magnetic particles S1 in a dispersed state and their magnetization curve. As shown in Figure 6(a), the magnetization curve of magnetic particles S1 in an aggregated state becomes a hysteresis curve due to the magnetic interaction of multiple magnetic particles S1. In contrast, as shown in Figure 6(b), in the dispersed state, the distance between multiple magnetic particles S1 increases and the magnetic interaction decreases. Therefore, the hysteresis property disappears.

[0059] As described above, when the spacing between multiple magnetic particles S1 changes due to the digestion of the crosslinking agent 72, the magnetization properties of the multiple magnetic particles S1 change. In this embodiment, the function of the digestate 4 is measured based on the magnetization properties of the multiple magnetic particles S1 that change in response to the digestion of the crosslinking agent 72. Figure 7(a) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in an aggregated state (before digestion of the crosslinking agent 72). Figure 7(b) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in a dispersed state (after digestion of the crosslinking agent 72).

[0060] As shown in Figures 7(a) and 7(b), the signal intensity of the frequency spectrum of the magnetic signal MS1 in the aggregated state is relatively high, while the signal intensity of the frequency spectrum of the magnetic signal MS1 in the dispersed state is relatively low. The analysis unit 40 can evaluate the degree of digestion of the crosslinking agent 72 through these changes in the frequency spectrum of the magnetic signal MS1.

[0061] Furthermore, the analysis unit 40 may evaluate the degree of digestion of the crosslinking agent 72 based on the phase spectrum of the magnetic signal MS1. The phase spectrum is obtained by performing a fast Fourier transform on the magnetic signal MS1. For example, Figure 7(c) shows an example of the phase spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in an aggregated state (before digestion of the crosslinking agent 72). Figure 7(d) shows an example of the phase spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in a dispersed state (after digestion of the crosslinking agent 72).

[0062] As shown in Figures 7(c) and 7(d), the signal intensity of the phase spectrum of the magnetic signal MS1 in the aggregated state is relatively low, while the signal intensity of the phase spectrum of the magnetic signal MS1 in the dispersed state is relatively high. The analysis unit 40 can evaluate the degree of digestion of the crosslinking agent 72 through these changes in the phase spectrum of the magnetic signal MS1.

[0063] One embodiment of the digestion function measurement system 1 may include a hydrophilic agent 74. As shown in Figures 8(a) and 8(b), the hydrophilic agent 74 forms a hydrophilic layer on the surface of the magnetic particles S1, preventing contact between multiple magnetic particles S1. The hydrophilic agent 74 is, for example, a hydrophilic polymer that can be digested by the digesting fluid 4. As the digestible hydrophilic polymer, for example, a cross-linked dextran lactose polymer is used. Before the digestion of the hydrophilic agent 74, the multiple magnetic particles S1 are separated from each other and in a dispersed state. When the hydrophilic agent 74 is digested by the digesting fluid 4, the multiple hydrophobic magnetic particles S1 gather together and become aggregated. As described above, when the spacing between multiple magnetic particles S1 changes due to the digestion of the hydrophilic agent 74, the magnetization characteristics of the multiple magnetic particles S1 change. The analysis unit 40 measures the function of the digesting fluid 4 based on the magnetization characteristics of the multiple magnetic particles S1 that change in response to the digestion of the hydrophilic agent 74.

[0064] For example, Figure 9(a) shows magnetic particles S1 in a dispersed state and their magnetization curve, and Figure 9(b) shows magnetic particles S1 in an aggregated state and their magnetization curve. As shown in Figure 9(a), the magnetic particles S1 in a dispersed state have wide spacing between them and weak magnetic interaction, so their magnetization curve does not exhibit hysteresis characteristics. In contrast, as shown in Figure 9(b), the magnetization curve of magnetic particles S1 in an aggregated state becomes a hysteresis curve due to the magnetic interaction between the multiple magnetic particles S1.

[0065] As described above, when the spacing between multiple magnetic particles S1 changes due to the digestion of the hydrophilic agent 74, the magnetization properties of the multiple magnetic particles S1 change. In one embodiment, the function of the digestate 4 is measured based on the magnetization properties of the multiple magnetic particles S1 that change in response to the digestion of the hydrophilic agent 74. Figure 10(a) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in a dispersed state (before digestion of the hydrophilic agent 74). Figure 10(b) shows an example of the frequency spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in an aggregated state (after digestion of the hydrophilic agent 74).

[0066] As shown in Figures 10(a) and (b), the signal intensity of the frequency spectrum of the magnetic signal MS1 in the dispersed state is relatively low, while the signal intensity of the frequency spectrum of the magnetic signal MS1 in the aggregated state is relatively high. The analysis unit 40 can evaluate the degree of digestion of the hydrophilic agent 74 through these changes in the frequency spectrum of the magnetic signal MS1.

[0067] Furthermore, the analysis unit 40 may evaluate the degree of digestion of the hydrophilic agent 74 based on the phase spectrum of the magnetic signal MS1. The phase spectrum is obtained by performing a fast Fourier transform on the magnetic signal MS1. For example, Figure 10(c) shows an example of the phase spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in a dispersed state (before digestion of the hydrophilic agent 74). Figure 10(d) shows an example of the phase spectrum of the magnetic signal MS1 observed when an external magnetic field H(t) is applied to magnetic particles S1 in an aggregated state (after digestion of the hydrophilic agent 74).

[0068] As shown in Figures 10(c) and (d), the signal intensity (absolute value) of the phase spectrum of the magnetic signal MS1 in the dispersed state is relatively high, while the signal intensity (absolute value) of the phase spectrum of the magnetic signal MS1 in the aggregated state is relatively low. The analysis unit 40 can evaluate the degree of digestion of the crosslinking agent 72 through such changes in the phase spectrum of the magnetic signal MS1.

[0069] Next, a digestive function measurement system 1A according to another embodiment will be described. Figure 11 is a schematic diagram showing a digestive function measurement system 1A according to another embodiment. The digestive function measurement system 1A includes a digestive function measurement device 2A instead of the digestive function measurement device 2. In the following, the differences from the digestive function measurement device 2 will be mainly explained, and redundant explanations will be omitted.

[0070] As shown in Figure 11, in the digestive function measuring device 2A, the reference magnetic particle S0 located in the reference region RR is exposed to a digestive fluid 5 that is different from the digestive fluid 4 to which the magnetic particle S1 is exposed. Typically, the measurement region MR is an in vivo region, and the reference region RR is an extra vivo region.

[0071] The digestive function measuring device 2A further comprises a function adjustment unit 52 and a function measuring unit 53. The function adjustment unit 52 adjusts the digestive function of the digestive fluid 5, for example, the activity of the digestive fluid 5. When measuring the acidity of the digestive fluid 4 as a digestive function, the function adjustment unit 52 supplies hydrochloric acid or sodium hydroxide to the digestive fluid 5 in the reference region RR to adjust the acidity of the digestive fluid 5. The function measuring unit 53 measures the digestive function of the digestive fluid 5. For example, the function measuring unit 53 is a pH meter and measures the acidity of the digestive fluid 5.

[0072] Furthermore, when measuring the activity of digestive enzymes in the digestive fluid 4 as part of the digestive function, the function adjustment unit 52 may supply an enzyme activator, enzyme inhibitor, or digestive enzyme to the digestive fluid 5 in the reference region RR to adjust the digestive activity of the digestive fluid 5. In this case, the function measurement unit 53 measures the activity state of the digestive enzymes in the digestive fluid 5.

[0073] The digestive function measuring device 2A measures the digestive function of digestive fluid 4 placed in the measurement area MR based on a difference signal DS, which represents the difference between the magnetic signal MS1 and the reference signal MS2. Figure 12(a) shows an example of the waveform of the reference signal MS2, and Figure 12(b) shows an example of the waveform of the magnetic signal MS1. Figure 12(c) shows an example of the waveform of the difference signal DS, which represents the difference between the reference signal MS2 shown in Figure 12(a) and the magnetic signal MS1 shown in Figure 12(b).

[0074] The function adjustment unit 52 of the digestive function measuring device 2A adjusts the digestive function of the digestive fluid 5 so that the difference signal DS is minimized. As shown in Figures 12(a) and 12(b), when the reference signal MS2 and the magnetic signal MS1 have the same waveform, the voltage value (signal value) of the difference signal DS becomes 0, which is the minimum value, as shown in Figure 12(c). When the voltage value of the difference signal DS becomes 0, it is inferred that the digestive function of digestive fluid 4 and the digestive function of digestive fluid 5 are the same. Therefore, the analysis unit 40 of the digestive function measuring device 2A changes the digestive function of digestive fluid 5 by the function adjustment unit 52, identifies the digestive function of digestive fluid 5 that minimizes the difference signal DS, and determines the identified digestive function as the digestive function of digestive fluid 4. For example, the analysis unit 40 determines the acidity of digestive fluid 5 measured by the function measuring unit 53 when the difference signal DS is minimized as the acidity of digestive fluid 4.

[0075] The digestive function measuring device 2A can measure the digestive function of digestive fluid 4 without frequency domain analysis by identifying the digestive function of digestive fluid 5 that minimizes the difference signal DS as the digestive function of digestive fluid 4. Therefore, the computational load of the digestive function measuring device 2A can be reduced, and the digestive function of digestive fluid 4 can be measured at high speed.

[0076] In one embodiment, the digestive function measuring device 2A may include a control circuit 80. The control circuit 80 is an analog circuit such as a PID control circuit or an operational amplifier comparator circuit. The control circuit 80 is connected to the function adjustment unit 52 and the function measuring unit 53, and controls the function adjustment unit 52 to adjust the digestive function of the digestive fluid 5 so that the voltage value of the difference signal DS becomes 0. By adjusting the digestive function of the digestive fluid 5 using the control circuit 80 instead of the analysis unit 40, the computational load on the analysis unit 40 can be reduced, and the measurement delay can be reduced. When using the control circuit 80, the above logic can be executed without using the analysis unit 40.

[0077] In this embodiment, even if the measurement region MR is a region within a living organism and the digestive function of digestive fluid 4 cannot be directly measured using a measuring instrument such as a pH meter, the digestive function of digestive fluid 4 can be measured through the digestive function of digestive fluid 5 measured using a measuring instrument.

[0078] Next, a digestive function measurement system 1B according to another embodiment will be described. Figure 13 is a schematic diagram showing a digestive function measurement system 1B according to another embodiment. The digestive function measurement system 1B includes a digestive function measurement device 2B instead of the digestive function measurement device 2. In the following, the differences from the digestive function measurement device 2 will be mainly explained, and redundant explanations will be omitted.

[0079] As shown in Figures 13 and 14, the digestive function measuring device 2B further comprises an image generation unit 60 and a drive unit 62. The drive unit 62 includes an actuator for moving the measuring unit 10, for example, moving the measuring unit 10 in a two-dimensional direction perpendicular to the irradiation direction of the external magnetic field H(t). The drive unit 62 only needs to move the measuring unit 10 relative to the measuring area MR, and may be configured to move an object (e.g., a human body) containing the measuring area MR relative to the measuring unit 10.

[0080] The analysis unit 40 acquires the magnetic signal MS1 at each position of the measurement unit 10 moved by the drive unit 62. The magnetic signal MS1 measured at each position of the measurement unit 10 is recorded in the storage unit 50. By measuring the magnetic signal MS1 while moving the measurement unit 10, information showing the relationship between the position of the measurement unit 10 and the signal strength of the magnetic signal MS1 is generated.

[0081] The image generation unit 60 generates an intensity distribution image Im showing the intensity distribution of the magnetic signal MS1 based on the signal intensity of the magnetic signal MS1 measured at each location. The intensity distribution of the magnetic signal MS1 is visually represented by using appropriate interpolation methods and color mapping during imaging. For example, the image generation unit 60 divides the measurement area MR into a grid and represents the signal intensity at each grid point as the brightness of each pixel in the intensity distribution image Im. Alternatively, the intensity at each grid point may be represented as the color of the intensity distribution image Im. For example, areas with low signal intensity are represented as dark colors, and areas with high signal intensity are represented as bright colors. Since the signal intensity of the magnetic signal MS1 increases at locations where magnetic particles S1 are present, the intensity distribution image Im can also be said to show the distribution of magnetic particles S1. By generating the intensity distribution image Im, the distribution of magnetic particles S1 can be visually understood. Figure 15 shows an example of an intensity distribution image Im showing the distribution of magnetic particles S1.

[0082] The image generation unit 60 may periodically generate intensity distribution images Im, and may generate multiple intensity distribution images Im arranged in a time series. The digestion process of magnetic particles S1 can be visually evaluated from the multiple intensity distribution images Im arranged in a time series.

[0083] In one embodiment, as shown in Figure 13, the digestive function measuring device 2B may further include an image analysis unit 64 that analyzes intensity distribution images Im to acquire various parameters indicating the function of the digestive system. For example, the image analysis unit 64 analyzes a plurality of intensity distribution images Im arranged in a time series and identifies the position of the magnetic particle S1 at each time from the brightness values ​​of the plurality of intensity distribution images Im. The image analysis unit 64 then acquires the movement velocity of the magnetic particle S1 in the digestive tract from the position of the magnetic particle S1 at each time. For example, as shown in Figure 16, the image analysis unit 64 identifies the movement trajectory of the magnetic particle S1 from the position information of the magnetic particle S1 at time ti (i=1,2,···,I), and acquires the movement velocity of the magnetic particle S1 by dividing the distance traveled by the magnetic particle S1 along the movement trajectory by the travel time. The movement velocity of the magnetic particle S1 in the digestive tract is an important parameter indicating the function of the digestive system.

[0084] Furthermore, the image analysis unit 64 may obtain at least one of the following based on the distribution of brightness values ​​of multiple intensity distribution images Im: the time required from administration to disintegration of the transport carrier 70, the disintegration location of the transport carrier 70, and the amount of magnetic particles S1 released from the transport carrier 70. Figures 17(a) to (c) show the intensity distribution images Im at times t1, t2, and t3, respectively. Note that time t2 is later than time t1, and time t3 is later than time t2. As shown in Figures 17(a) and (b), at times t1 and t2, multiple magnetic particles S1 are concentrated in localized areas, indicating that the multiple magnetic particles S1 remain within the transport carrier 70. In contrast, in Figure 17(c), multiple magnetic particles S1 are dispersed over a wide area, indicating that the transport carrier 70 has disintegrated. In this way, the image analysis unit 64 identifies the disintegration location of the transport carrier 70 and the time required to disintegrate from the dispersion of magnetic particles S1 in a specific region. Furthermore, the image analysis unit 64 determines the amount of magnetic particles S1 emitted from the ratio of the sum of brightness values ​​in the region where the brightness value is above a reference value to the sum of brightness values ​​in the region where the brightness value is below a reference value.

[0085] The image analysis unit 64 may analyze the intensity distribution image Im to evaluate whether the drug encapsulated in the transport carrier 70 is adequately protected from the digestive fluid 4, and whether it has successfully passed through the digestive tract (not only overall, but also locally, for example, whether it was protected from stomach acid and safely reached the duodenum). If multiple magnetic particles S1 are uniformly distributed in the tablet, the size of the tablet can be measured from the intensity distribution image Im, making it possible to evaluate the dissolution rate of the tablet. It is also possible to evaluate whether the capsule was excreted from the body without disintegrating.

[0086] Furthermore, the image analysis unit 64 may analyze multiple intensity distribution images Im to identify the distribution of multiple magnetic particles S1 at each time point, and obtain information indicating the inner diameter of the digestive tract based on the distribution of multiple magnetic particles S1 at each time point. For example, as shown in Figure 18, a quantitative amount of gel G containing multiple magnetic particles S1 is administered orally, and magnetic imaging is performed. The magnetic particles S1 uniformly dispersed in the gel G make it possible to visualize the gel G. The gel G allows the penetration of digestive fluid 4, but prevents leakage of magnetic particles S1 from the outside using indigestible dietary fiber, and has a fibrous structure that maintains the overall size of the gel G even when exposed to digestive fluid 4. The magnetic particles S1 dispersed in the gel G are gradually digested, but the gel G itself is not digested.

[0087] Figures 19(a) to (d) each show an example of an intensity distribution image Im indicating the distribution of magnetic particles S1. As shown in Figures 19(a) to (d), the shape of the quantitative gel G mass directly reflects the inner diameter of the digestive tract, becoming narrower or rounder depending on the inner diameter of the digestive tract. Figures 19(a) and (b) show the distribution of magnetic particles S1 placed in a digestive tract with a narrow inner diameter. Figure 19(a) is the intensity distribution image Im of magnetic particles S1 before digestion, and Figure 19(b) is the intensity distribution image Im of magnetic particles S1 during digestion. Figures 19(c) and (d) show the distribution of magnetic particles S1 placed in a digestive tract with a wide inner diameter. Figure 19(c) is the intensity distribution image Im of magnetic particles S1 before digestion, and Figure 19(d) is the intensity distribution image Im of magnetic particles S1 during digestion.

[0088] As described above, in this image analysis, (1) changes in signal intensity (image brightness values) reflect corrosion and digestion by gastric acid and enzymes, and (2) the quantitative shape of gel G reflects the local shape of the gastrointestinal lumen, and both types of information can be obtained from a single image. This method is superior in terms of safety and simplicity compared to CT imaging using barium contrast, as there are no concerns about radiation exposure.

[0089] Next, with reference to Figure 20, a digestive function measurement method according to one embodiment will be described. The digestive function measurement method MT1 shown in Figure 20 is performed using the digestive function measurement device 2B. Figure 20 is a flowchart of the digestive function measurement method MT1 according to one embodiment. In the digestive function measurement method MT1, the function of the digestive fluid 4 is measured using magnetic particles S1.

[0090] In this digestive function measurement method MT1, first, the magnetic field generator 11 of the measurement unit 10 applies an external magnetic field H(t) whose magnetic field strength changes over time to the measurement region MR (step ST1). The external magnetic field H(t) has a magnetic field strength of, for example, 1 kA / m to 30 kA / m and a frequency of 0.1 kHz to 300 kHz. The magnetization of the magnetic particles S1 placed in the measurement region MR changes in response to the applied external magnetic field H(t). Similarly, the magnetic field generator 21 of the reference unit 20 applies an external magnetic field H(t) whose magnetic field strength changes over time to the reference region RR.

[0091] Next, the receiving unit 12 of the measurement unit 10 detects the magnetic signal MS1, and the receiving unit 22 of the reference unit 20 detects the reference signal MS2 (step ST2). The magnetic signal MS1 is a signal that includes a magnetization response signal showing the magnetization response of the magnetic particle S1 to the external magnetic field H(t). The reference signal MS2 is a signal that includes a magnetization response signal showing the magnetization response of the reference magnetic particle S0 to the external magnetic field H(t).

[0092] Next, the processing unit 30 acquires a difference signal DS representing the difference between the magnetic signal MS1 and the reference signal MS2 (step ST3). More specifically, in step ST3, after noise components are removed from the magnetic signal MS1 and the reference signal MS2 by the filter 31, the difference signal DS representing the difference between the magnetic signal MS1 and the reference signal MS2 is generated by the operational amplifier 32. The difference signal DS output from the operational amplifier 32 is converted into digital data by the AD converter 33.

[0093] Next, the analysis unit 40 acquires parameters indicating the digestive function of the digestive fluid 4 based on the time-dependent changes in the difference signal DS output from the AD converter 33 (step ST4). For example, the analysis unit 40 performs a fast Fourier transform on the difference signal DS with respect to the time variable to generate a frequency spectrum of the difference signal DS, and identifies the degree of digestion (particle size) of the magnetic particles S1 based on the signal intensity of the generated frequency spectrum. Alternatively, the analysis unit 40 may acquire the acidity of the digestive fluid 4 from the time-series change in the degree of digestion of the magnetic particles S1. The analysis unit 40 may also generate a phase spectrum of the difference signal DS and acquire parameters indicating the digestive function of the digestive fluid 4 based on the time-dependent changes in the difference signal DS, which change according to the degree of dispersion of the magnetic particles S1 due to the digestion of the crosslinking agent 72 or the hydrophilic agent 74.

[0094] In one embodiment, after step ST4, the drive unit 62 may be driven and the measurement unit 10 may be moved relative to the measurement area MR (step ST5). For example, the drive unit 62 moves the measurement unit 10 in a two-dimensional direction perpendicular to the irradiation direction of the external magnetic field H(t). Next, it is determined whether or not a magnetic signal MS1 is detected at all positions in the two-dimensional direction (step ST6). If a magnetic signal MS1 is not detected at all positions, the processes of steps ST1 to ST5 are repeated until a magnetic signal MS1 is detected at all positions.

[0095] When a magnetic signal MS1 is detected at all positions in the two-dimensional direction, the image generation unit 60 generates an intensity distribution image Im that shows the distribution of signal intensity of the magnetic signal MS1 acquired at each position in the two-dimensional direction (step ST7).

[0096] As explained above, the digestive function measurement method MT1 described above can non-invasively measure the digestive function of digestive fluid 4 by utilizing the magnetization response that changes according to the degree of digestion of magnetic particles S1 by digestive fluid 4. In addition, by generating an intensity distribution image Im that shows the distribution of signal intensity of the magnetic signal MS1, the distribution of magnetic particles S1 can be visually understood.

[0097] Next, with reference to Figure 21, a digestive function measurement method MT2 according to another embodiment will be described. The digestive function measurement method MT2 shown in Figure 21 is performed using the digestive function measurement device 2A. Figure 21 is a flowchart of the digestive function measurement method MT2 according to one embodiment. In the following, the differences from the digestive function measurement method MT1 will be mainly explained, and redundant explanations will be omitted.

[0098] In the digestive function measurement method MT2, first, the magnetic field generator 11 of the measurement unit 10 applies an external magnetic field H(t) whose magnetic field strength changes over time to the measurement region MR (step ST11). Similarly, the magnetic field generator 21 of the reference unit 20 applies an external magnetic field H(t) whose magnetic field strength changes over time to the reference region RR. Next, the receiving unit 12 of the measurement unit 10 detects the magnetic signal MS1, and the receiving unit 22 of the reference unit 20 detects the reference signal MS2 (step ST12). Next, the processing unit 30 acquires a difference signal DS that shows the difference between the magnetic signal MS1 and the reference signal MS2 (step ST13).

[0099] Next, the analysis unit 40 determines whether the intensity (effective value) of the difference signal DS is 0 or not (step ST14). If the intensity of the difference signal DS is not 0, the function adjustment unit 52 controls the acidity of the other digestive fluid 5 located in the reference region RR so that the intensity of the difference signal DS becomes 0 (step ST15). In other words, the analysis unit 40 adjusts the digestive function of the other digestive fluid 5 so that the magnetic signal MS1 and the reference signal MS2 have the same waveform.

[0100] In step ST14, when the intensity of the difference signal DS becomes 0, the analysis unit 40 obtains the acidity of another digested fluid 5 when the intensity of the difference signal DS is 0 from the function measurement unit 53 and determines it as the acidity of the digested fluid 4 (step ST16). Next, steps ST17 to ST19 are performed. The processing performed in steps ST17 to ST19 is the same as the processing performed in steps ST5 to ST7 of the digestive function measurement method MT1.

[0101] The digestive function measurement method MT2 measures the digestive function of digestive fluid 4 without frequency domain analysis, thereby reducing the computational load. Furthermore, the digestive function measurement method MT2 can be implemented as an analog circuit, and the digestive function of digestive fluid 4, which is effectively located in the measurement region MR, can be directly displayed by a measuring instrument (e.g., a pH meter) that measures the digestive function of digestive fluid 5, which is located in the reference region RR. In other words, by synchronizing the states of the two digestive fluids, the digestive function measurement method MT2 allows for the effective measurement of the digestive function of digestive fluid 4 in the measurement region MR (e.g., inside the human body or in areas where measuring instruments cannot be inserted), through the reference region RR, to which measuring instruments can be applied. Magnetic "synchronization" enables a digestive function measurement method that is normally inapplicable.

[0102] Although various embodiments of the digestive function measurement systems 1, 1A, 1B, digestive function measurement devices 2, 2A, 2B, and digestive function measurement methods have been described above, various modified forms can be constructed without changing the gist of the invention, and the invention is not limited to the embodiments described above.

[0103] For example, in the above embodiment, the magnetic signal MS1 and the reference signal MS2 are received from the measurement unit 10 and the reference unit 20, and the digestive function of the digestive fluid 4 is measured using the difference signal DS, which shows the difference between the magnetic signal MS1 and the reference signal MS2. However, the digestive function measuring devices 2, 2A, and 2B do not necessarily have a reference unit 20. For example, information showing the waveform of the reference signal MS2 may be stored in advance in the storage unit 50, and the difference between the magnetic signal MS1 acquired by the measurement unit 10 and the reference signal MS2 read from the storage unit 50 may be acquired as the difference signal DS.

[0104] Furthermore, although the embodiments described above mainly described examples of measuring the function of human digestive fluids, the digestive function measurement systems 1, 1A, 1B, digestive function measurement devices 2, 2A, 2B, and digestive function measurement methods can also measure the function of digestive fluids of animals other than humans. Note that the digestive fluids do not necessarily have to be of biological origin; for example, the digestive function measurement systems 1, 1A, 1B, digestive function measurement devices 2, 2A, 2B, and digestive function measurement methods can also measure the acidity of corrosive wastewater from outside the drainpipe.

[0105] In the embodiment described above, the analysis unit 40 performs a Fourier transform on the difference signal DS with respect to the time variable and performs frequency domain analysis on the magnetization response signal included in the magnetic signal MS1. However, in one embodiment, the analysis unit 40 may obtain parameters indicating the digestive function of the digestive fluid 4 from the magnetic signal MS1 using time domain analysis, harmonic analysis, phase analysis, intermodulation, or interference measurement. For example, the analysis unit 40 may obtain parameters indicating the digestive function of the digestive fluid 4 based on the signal intensity of the magnetic signal MS1.

[0106] The various embodiments described above can be combined in a non-consistent manner.

[0107] This disclosure includes the following:

[0108] [1] A digestive function measuring device for measuring the digestive function of digestive fluids, A measuring unit comprising: a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles placed in the digested liquid; and a receiving unit that detects a magnetic signal including a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field; An analysis unit that acquires parameters indicating the digestive function of the digestive fluid based on the magnetic signal received by the receiving unit, A digestive function measuring device equipped with the following features.

[0109] [2] A reference unit comprising: a magnetic field generating unit that applies the external magnetic field to one or more reference magnetic particles placed outside the digested liquid; and a receiving unit that detects a reference signal including a magnetization response signal indicating the magnetization response of the one or more reference magnetic particles to the external magnetic field; A processing unit that acquires a difference signal indicating the difference between the magnetic signal and the reference signal, Furthermore, The digestive function measuring device according to [1], wherein the analysis unit acquires parameters indicating the digestive function of the digestive fluid based on the difference signal.

[0110] [3] The digestive function measuring device according to [2], wherein the analysis unit obtains parameters indicating the digestive function of the digestive fluid based on the signal intensity in each frequency domain obtained by performing a Fourier transform of the difference signal with respect to the time variable.

[0111] [4] The digestive function measuring device according to [2] or [3], wherein the analysis unit obtains parameters indicating the digestive function of the digestive fluid based on the phases of each frequency domain obtained by performing a Fourier transform of the difference signal with respect to a time variable.

[0112] [5] Further comprising a storage unit for storing the difference signals observed when the external magnetic field is applied to the one or more magnetic particles placed in another digestive fluid having a known digestive function, A digestive function measuring device according to any one of [2] to [4], wherein parameters indicating the digestive function of the digestive fluid are obtained based on the correlation between the difference signal obtained by the processing unit and the difference signal stored in the storage unit.

[0113] [6] The digestive function measuring device according to any one of [1] to [5], wherein the analysis unit acquires the acidity of the digestive fluid as a parameter indicating the digestive function of the digestive fluid.

[0114] [7] The digestive function measuring device according to any one of [1] to [6], wherein the analysis unit acquires information indicating the particle size of the one or more magnetic particles as a parameter indicating the digestive function of the digestive fluid.

[0115] [8] A reference unit comprising: a magnetic field generating unit that applies the external magnetic field to one or more reference magnetic particles placed in another digestive fluid; and a receiving unit that detects a reference signal including a magnetization response signal indicating the magnetization response of the one or more reference magnetic particles to the external magnetic field, A function adjustment unit for adjusting the digestive function of the aforementioned other digestive fluid, A processing unit that acquires a difference signal indicating the difference between the magnetic signal and the reference signal, Furthermore, The digestive function measuring device according to [1], [6] and [7], wherein the analysis unit identifies the digestive function of the other digestive fluid that minimizes the difference signal while changing the digestive function of the other digestive fluid by the function adjustment unit, and determines the identified digestive function of the other digestive fluid as the digestive function of the digestive fluid.

[0116] [9] A drive unit for moving the measuring unit, An image generation unit generates an intensity distribution image showing the distribution of signal intensity of the magnetic signal detected by the measurement unit at each position, A digestive function measuring device according to any one of items [1] to [8], comprising the following:

[0117]

[10] The image generation unit periodically generates the intensity distribution images to generate a plurality of intensity distribution images arranged in time series, The digestive function measuring device according to [9], further comprising an image analysis unit that analyzes the plurality of intensity distribution images to identify the position of the one or more magnetic particles at each time point and acquires the movement velocity of the magnetic particles based on the position of the one or more magnetic particles at each time point.

[0118]

[11] The magnetic particles include a plurality of magnetic particles supported on a transport carrier, The digestive function measuring device according to

[10] , wherein the image analysis unit analyzes the plurality of intensity distribution images to obtain information indicating the time required from administration of the transport carrier to disintegration, the disintegration position of the transport carrier, and the amount of release of the plurality of magnetic particles.

[0119]

[12] The magnetic particles include a plurality of magnetic particles supported on a transport carrier, The image generation unit periodically generates the intensity distribution image to generate a plurality of intensity distribution images arranged in time series. The digestive function measuring device is an image analysis unit that analyzes the plurality of intensity distribution images to identify the distribution of the plurality of magnetic particles at each time point and acquires information indicating the inner diameter of the digestive tract based on the distribution of the plurality of magnetic particles at each time point, as described in any one of [9] to

[11] .

[0120]

[13] The digestive function measuring device according to any one of [1] to

[12] , wherein the receiving unit includes an induction coil, a Hall sensor, a magnetoresistive element, an optical pumping magnetometer, or a superconducting quantum interferometer.

[0121]

[14] The digestive function measuring device according to any one of [1] to

[13] , wherein the analysis unit obtains parameters indicating the digestive function of the digestive fluid using time-domain analysis, frequency-domain analysis, harmonic analysis, phase analysis method, intermodulation method, or interference measurement method of the magnetic signal.

[0122]

[15] A digestive function measuring system for measuring the digestive function of digestive fluids, One or more magnetic particles placed in the digestive fluid, A measuring unit comprising: a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles; and a receiving unit that detects a magnetic signal including a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field; An analysis unit that acquires parameters indicating the digestive function of the digestive fluid based on the magnetic signal received by the receiving unit, A digestive function measurement system equipped with the following features.

[0123]

[16] The one or more magnetic particles include a plurality of magnetic particles, The digestive function measurement system further comprises a crosslinking agent that is digestible by the digestive fluid and that binds the plurality of magnetic particles together to form aggregates. The digestive function measurement system according to

[15] , wherein the analysis unit obtains parameters indicating the digestive function of the digestive fluid based on the magnetic signal which changes according to the degree of dispersion of the plurality of magnetic particles due to the digestion of the crosslinking agent.

[0124]

[17] The one or more magnetic particles include a plurality of magnetic particles, The plurality of magnetic particles are coated with a hydrophilic agent that is digested by the digestive fluid. The digestive function measurement system according to

[13] or

[16] , wherein the analysis unit obtains parameters indicating the digestive function of the digestive fluid based on the magnetic signal which changes according to the degree of condensation of the magnetic particles due to the digestion of the hydrophilic agent.

[0125]

[18] The steps include applying an external magnetic field whose magnetic field strength changes over time to one or more magnetic particles placed in the digestive fluid, The steps include detecting a magnetic signal that includes a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field, The steps include obtaining parameters indicating the digestive function of the digestive fluid based on the temporal changes in the magnetic signal, A method for measuring digestive function, including the following. [Explanation of Symbols]

[0126] 1,1A,1B...Digestive function measurement system, S1...Magnetic particles, 2,2A,2B...Digestive function measurement device, 4...Digestive fluid, 5...Another digestive fluid, 10...Measurement unit, 11,21...Magnetic field generation unit, 12,22...Receiving unit, 20...Reference unit, 30...Processing unit, 40...Analysis unit, 50...Storage unit, 60...Image generation unit, 62...Drive unit, 64...Image analysis unit, 70...Transport carrier, 72...Crosslinking agent, 74...Hydrophilic agent, DS...Differential signal, H...External magnetic field (t), Im...Intensity distribution image, MS1...Magnetic signal, MS2...Reference signal.

Claims

1. A device for evaluating drug delivery, A measuring unit comprising: a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to a transport carrier orally administered to a subject, wherein the transport carrier carries a drug and one or more magnetic particles; and a receiving unit that detects a magnetic signal including a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field; An analysis unit that acquires information regarding the delivery function of the drug carried on the transport carrier based on the magnetic signal received by the receiving unit, A device equipped with the following features.

2. A reference unit comprising: a magnetic field generating unit that applies the external magnetic field to one or more reference magnetic particles placed outside the body of the subject; and a receiving unit that detects a reference signal including a magnetization response signal indicating the magnetization response of the one or more reference magnetic particles to the external magnetic field; A processing unit that acquires a difference signal indicating the difference between the magnetic signal and the reference signal, Furthermore, The apparatus according to claim 1, wherein the analysis unit acquires information regarding the drug delivery function based on the difference signal.

3. The apparatus according to claim 2, wherein the analysis unit obtains information regarding the drug delivery function based on the signal intensity in each frequency domain obtained by performing a Fourier transform of the difference signal with respect to a time variable.

4. The apparatus according to claim 2, wherein the analysis unit obtains information regarding the drug delivery function based on the phases of each frequency domain obtained by performing a Fourier transform of the difference signal with respect to a time variable.

5. The system further includes a storage unit that stores the difference signal observed when the external magnetic field is applied to the one or more magnetic particles placed in a digestive fluid having a known digestive function, The apparatus according to claim 2, wherein information regarding the drug delivery function is obtained based on the correlation between the difference signal obtained by the processing unit and the difference signal stored in the storage unit.

6. The apparatus according to claim 1, wherein the analysis unit acquires information indicating the particle size of the one or more magnetic particles as information relating to the drug delivery function.

7. A drive unit for moving the aforementioned measuring unit, An image generation unit generates an intensity distribution image showing the distribution of signal intensity of the magnetic signal detected by the measurement unit at each position, The apparatus according to claim 1, comprising:

8. The image generation unit periodically generates the intensity distribution image to generate a plurality of intensity distribution images arranged in time series. The apparatus according to claim 7, further comprising an image analysis unit that analyzes the plurality of intensity distribution images to determine the position of the transport carrier that carries the one or more magnetic particles at each time point.

9. The apparatus according to claim 8, wherein the image analysis unit obtains the movement speed of the transport carrier based on the positions of the one or more magnetic particles at each time point.

10. The apparatus according to claim 8, wherein the image analysis unit analyzes the plurality of intensity distribution images to obtain at least one of the following: information indicating the time required from administration of the transport carrier to disintegration, information indicating the disintegration position of the transport carrier, and information indicating the amount of magnetic particles released.

11. The apparatus according to claim 8, wherein the image analysis unit analyzes the intensity distribution image to determine whether the drug carried on the transport carrier is protected from the subject's digestive fluid.

12. The apparatus according to claim 8, wherein the image analysis unit analyzes the intensity distribution image to determine whether or not the transport carrier has been expelled from the subject's body.

13. The apparatus according to claim 1, wherein the transport carrier is a capsule, tablet, or gel carrier.

14. The transport carrier is a tablet, The apparatus according to claim 8, wherein the image analysis unit analyzes the intensity distribution image to determine the dissolution rate of the tablet.

15. The apparatus according to claim 1, wherein the receiving unit includes an induction coil, a Hall sensor, a magnetoresistive element, an optical pumping magnetometer, or a superconducting quantum interferometer.

16. The apparatus according to claim 1, wherein the analysis unit acquires information regarding the drug delivery function using time-domain analysis, frequency-domain analysis, harmonic analysis, phase analysis method, intermodulation method, or interference measurement method of the magnetic signal.

17. A system for evaluating drug delivery, A transport carrier that carries a drug and one or more magnetic particles, A measurement unit comprising: a magnetic field generating unit that applies an external magnetic field whose magnetic field strength changes over time to the transport carrier orally administered to a subject; and a receiving unit that detects a magnetic signal including a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field; An analysis unit that acquires information regarding the delivery function of the drug carried on the transport carrier based on the magnetic signal received by the receiving unit, A system equipped with these features.

18. A method for evaluating drug delivery, The steps include: administering a drug and a carrier carrying one or more magnetic particles orally to a subject; The steps include applying an external magnetic field to the transport carrier, the magnetic field strength of which changes over time, The steps include detecting a magnetic signal that includes a magnetization response signal indicating the magnetization response of the one or more magnetic particles to the external magnetic field, A step of obtaining information regarding the delivery function of the drug carried on the transport carrier based on the change in the magnetic signal over time, Methods that include...

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