JP2020070246A - Device and method for detecting composition for oral administration, and composition for oral administration - Google Patents

Abstract

To provide a composition for oral administration that can confirm whether or not the composition for oral administration comprising a magnetic material detectable by a magnetoresistive effect element is taken or ingested, and to provide a device and a method for detecting the same.SOLUTION: The above problem is solved by a composition 20 for oral administration comprising a magnetic material detectable by a magnetoresistive effect element 10 placed outside the body. The composition 20 for oral administration is preferably pharmaceuticals, health foods, functional foods, nutritional supplementary foods, supplements, foods with health claims, foods for specified health uses, foods with nutrient function claims, foods with functional claims, and the like. The magnetic material is preferably iron oxide. A detection device 1 is a device for detecting the composition 20 for oral administration, having the magnetoresistive effect element 10 for detecting whether or not the composition 20 for oral administration is present in the digestive tract and configured so that the magnetoresistive effect element 10 oscillates.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an orally administrable composition, a detection device and a detection method for the orally administrable composition, which can confirm whether or not the orally administered composition is taken or ingested.

  It is desirable that a composition for oral administration such as a pharmaceutical product be sure to take a predetermined amount at a predetermined date and time in order to exert a predetermined effect. In addition to forgetting to take the drug, overdose or repeated dosing may result in the inability to obtain the effects of medicines and the like and disturb the doctor's treatment plan. In response to these problems, patients have been instructed to record the medication status in a memo or the like to prevent forgetting to drink or repeated drinking.

  However, if the patient himself / herself should be able to record properly, he / she may forget to record or make inaccurate records, and it was difficult to say enough for medication management. In order to solve such problems, in recent years, various medication management utilizing application software of smartphones have been proposed.

  As an example, in Patent Document 1, even if a nursing care facility staff member or a patient misses the medication at the time of medication, the visiting pharmacy can grasp the medication in real time, manage the medication, and prevent forgetting to take the medication. A medication management system and a medication detection device used therefor have been proposed. This medication management system is provided with four rows of pockets on the surface, an infrared sensor that senses the presence or absence of medication stored in each pocket, an LED light that lights up when the medication is taken, and an infrared sensor. And a medication detection device body including control means for controlling the LED light, and control information of the control means is set via a network, and information about the presence or absence of medication stored in the pocket is displayed on the display screen. It is composed of a terminal device and a database for storing the control information and the data obtained from the infrared sensor.

  On the other hand, Patent Document 2 proposes a device for measuring compliance of drug therapy by detecting intake of a drug containing a drug and a permanent magnet. The apparatus includes at least two magnetic field sensors spaced apart from each other on a necklace, each magnetic field sensor receiving a signal from the magnetic field sensor to determine the passage of a permanent magnet between the magnetic field sensors. It is in electronic communication with the processor. In this device, the tracer is a small disk-shaped rare earth permanent magnet coated with a biocompatible material based on silicone or other polymer, which produces a magnetic field through the tissue and passes through the esophagus. It acts to provide the detector with the necessary information about the movement of the dose of medication involved. The detection device is a wearable high resolution magnetic field sensor array placed around the neck and is said to be able to detect the tracer as it passes through the esophagus, regardless of its orientation. As the magnetic field sensor, Hall effect, magnetic-resistance type and magnetic-induction type sensors can be used, and the magnetic-induction type sensor is said to be preferable.

JP, 2018-94440, A JP, 2009-535103, A

  However, the technology described in Patent Document 1 may not be able to sufficiently administer medication except for patients who can operate smartphones and handle application software. Further, since the technique described in Patent Document 2 uses a disc-shaped rare earth permanent magnet as a tracer, it is necessary to consider the shape restriction and the influence of a large coercive force of the permanent magnet. Further, the two magnetic field sensors provided separately on the necklace detect the tracer when passing through the esophagus, but there is a possibility that the tracer passes quickly and cannot be accurately detected.

  The present invention has been made to solve the above problems, and its purpose is to take or ingest various compositions for oral administration, such as drug administration status, health food or functional food intake status, etc. An object of the present invention is to provide a composition for oral administration, a detection device and a detection method for the same, which can be confirmed.

  (1) The composition for oral administration according to the present invention is characterized by containing a magnetic material that can be detected by a magnetoresistive effect element placed outside the body.

  Since the composition for oral administration according to the present invention contains a magnetic material, the composition for oral administration existing in the digestive tract can be detected by vibrating the magnetoresistive effect element arranged outside the body. As a result, it can be confirmed that the composition for oral administration was orally administered. For example, by outputting the detection record such as the detection time, the family, doctor, nurse, caregiver, etc. can take medications. You can also check the intake status of health foods and functional foods. The magnetic material contained in the composition for oral administration can be preferably used because it is a magnetizable magnetic material having no large coercive force. The magnetizable magnetic material may be magnetized after the production of the composition for oral administration containing it, or may be magnetized before the production, even before being detected by the detection device according to the present invention. So long as it is magnetized.

  In the composition for oral administration according to the present invention, the magnetic material contained is not particularly limited as long as it is magnetizable and can be detected by a magnetoresistive effect element, but iron oxide is preferable. Iron oxide is known as an additive for medicines and foods, and is a substance that can be taken orally.

  The composition for oral administration according to the present invention is a drug, a health food, a functional food, a dietary supplement, a supplement, a food with health claims, a food for specified health uses, a nutritionally functional food, or a food with functional claims. By doing so, it is possible to confirm the medication status and the intake status of health foods and functional foods. The shape of the composition for oral administration is not particularly limited as long as it exhibits the effects of the present invention, and examples thereof include tablets, capsules, and granules.

  The magnetic material contained in the composition for oral administration according to the present invention may be contained in the composition for oral administration or may cover the surface of the composition for oral administration, It may be printed on the surface of the composition or a combination thereof. By doing so, the magnetic material can be included in the composition for oral administration in various forms.

  (2) The composition detecting device for oral administration according to the present invention is a device for detecting the composition for oral administration according to the present invention, and whether or not the composition for oral administration is present in the digestive tract. Is provided, and the magnetoresistive effect element vibrates.

  According to the present invention, it is possible to detect whether or not a composition for oral administration containing a magnetic material is present in the digestive tract. As a result, it is possible to confirm whether or not the composition for oral administration is taken or ingested, and for example, by outputting detection information such as the detection time thereof, other than the patient, family, doctor, nurse, caregiver, etc. Can check the medication status and intake status of health foods and functional foods. In the present invention, "the composition for oral administration exists in the digestive tract" means not only when the composition for oral administration exists in a state before administration, but also when it decomposes in the digestive tract and exists in a dissolved state. Is also included.

  In the composition detecting device for oral administration according to the present invention, the magnetoresistive effect element is selected from the front-rear direction, the left-right direction, the vertical direction and the oblique direction with respect to the composition for oral administration in the digestive tract. Amplifies in the above direction. By doing so, even if the composition for oral administration is in a static or substantially static state in the digestive tract, the composition for oral administration containing a magnetic material can be easily detected by oscillating the magnetoresistive effect element. it can.

  In the composition detecting device for oral administration according to the present invention, the vibration frequency of the amplitude of the magnetoresistive effect element is within a range of 1 to 200 Hz. A frequency range with less noise such as external noise and in-device noise generated from an electric circuit or a motor is preferable, and a particularly preferable frequency range is within a range of 1 to 20 Hz. By doing so, it is possible to avoid overlapping with noise, and it is possible to detect that the composition for oral administration is being taken or ingested, with the influence of noise being suppressed as much as possible.

  (3) The method for detecting a composition for oral administration according to the present invention is a method for detecting the composition for oral administration according to the present invention, which is performed in a digestive tract by a detection device equipped with a magnetoresistive effect element capable of amplitude. It is characterized by detecting whether or not the composition for oral administration is present.

  In the method for detecting a composition for oral administration according to the present invention, one or two or more of the detection devices are installed at any position of a torso including a chest and an abdomen. By doing so, it can be provided at a necessary place according to the circumstances of the person to be detected, and the medication status and intake status of the composition for oral administration can be accurately confirmed.

  According to the present invention, by a configuration different from the conventional medication management means, it is possible to confirm whether or not various compositions for oral administration have been taken or ingested, such as the medication status of medicines, the intake status of health foods and functional foods, etc. It is possible to provide a composition for oral administration, a detection device and a detection method thereof.

It is a schematic diagram which shows the aspect which equips with the detection apparatus of the composition for oral administration which concerns on this invention. It is an example of the composition for oral administration containing a magnetic material. It is a measurement result of the residual magnetization when a magnetic material is included in the composition for oral administration in the forms of FIGS. 2 (A) to (H). This is the relationship between the type of magnetic material and the residual magnetization. This is the relationship between the blending amount of the magnetic material and the residual magnetization. It is a block diagram which shows an example of a magnetoresistive effect element. It is a result of a detection experiment with a TMR element when a tablet sample passes through a rubber tube. It is a detection result when a tablet sample is ingested, (A) is a result when the detection device is installed at the position of the neck, and (B) is a result when the detection device is installed at the position of the stomach. It is a result when vibrating a detection apparatus at 3 Hz-13.33 Hz. The result of FIG. 9 is the result after the zero correction with the average value and the band-pass filter processing. It is a result (A) when the detection device is oscillated in a range of 1 mm to 4 mm, and a result (B) after the result is zero-corrected by an average value and band-pass filtered. It is a result of fitting by the inverse square attenuation and the dependence of the magnetic field strength on the x direction distance at y = 0.0 mm and z = 0.0 mm.

  The composition for oral administration according to the present invention, the detection device and the detection method thereof will be described with reference to the drawings. The present invention is not limited to the illustrated embodiment.

[Composition for Oral Administration, Detection Device and Detection Method Therefor]
The composition for oral administration 20 according to the present invention is characterized by containing a magnetic material detectable by a magnetoresistive effect element (hereinafter also referred to as a TMR element) 10 arranged outside the body. Examples of the composition for oral administration include medicines, health foods, functional foods, dietary supplements, supplements, foods with health claims, foods for specified health uses, foods with nutritional functions, foods with functional claims, and the like.

  The present invention also provides an apparatus and method for detecting the above-mentioned composition 20 for oral administration. An orally administered composition detecting device 1 is, for example, as shown in FIG. 1, a device including a magnetoresistive effect element 10 for detecting whether or not the orally administered composition 20 is present in the digestive tract. The method for detecting the composition for administration is a method for detecting whether or not the composition 20 for oral administration is present in the digestive tract by the detection device 1 including the magnetoresistive effect element 10.

  Since the composition 20 for oral administration contains the magnetic material 21, the composition 20 for oral administration existing in the digestive tract can be detected by oscillating the magnetoresistive effect element 10 arranged outside the body. As a result, it can be confirmed that the composition 20 for oral administration has been orally administered, and for example, by outputting detection records such as the detection time thereof, other than the patient, the family, doctor, nurse, caregiver, etc. can take the medicine. You can check the status and intake status of health foods and functional foods. The magnetic material 21 contained in the composition 20 for oral administration can also be preferably used because it is a magnetizable magnetic material having no large coercive force. Furthermore, the detecting device and the detecting method of the composition for oral administration 20 can detect whether or not the composition for oral administration 20 including the magnetized magnetic material 21 exists in the digestive tract.

  The TMR element 10 does not detect the change in the angle of magnetization caused by the magnetostrictive effect, but has the antiparallel coupling film structure 15 (see FIG. 6) and is orally administered to the detection target at the measurement target site 50. The magnetic field generated from the composition 20 (see FIG. 1) is spatially detected, the change in the captured magnetic field is detected as an angle change of magnetization, and the angle change is read out as a change in resistance (change in current) by the TMR effect. That is.

  Hereinafter, each component of the composition for oral administration, the detection device and the detection method will be described in detail.

[Composition for oral administration]
The composition 20 for oral administration contains at least the composition material 22 and the magnetic material 21, as shown in FIG. The present invention is characterized in that the composition 20 for oral administration contains the magnetic material 21 detectable by the TMR element 10, and the magnetic material 21 is detected by the TMR element 10.

(Composition material)
The composition material 22 is not particularly limited, and for example, in the case of a pharmaceutical product, in addition to the active ingredient, additives such as an excipient, a binder, a disintegrant, etc. may be contained. In addition, the health foods and functional foods may contain various auxiliary components and additives in addition to the main components of those foods.

(Magnetic material)
The magnetic material 21 needs to be harmless as a substance to be taken or ingested, and further needs to have magnetic characteristics that can be detected by the TMR element 10 even in a minute amount. In the present invention, it is desirable to use a known iron oxide as an additive for medicines and foods. As iron oxide, hematite (hematite, α-Fe ₂ O ₃ ), magnetite (magnetite, Fe ₃ O ₄ ), maghemite (maghemite, γ-Fe ₂ O ₃ ), limonite (limonite, Fe ₂ O _{3). · nH 2 O, n = 0.5~4} ), mention may be made of metaphosphoric acid treatment such as magnetite. Among them, magnetite (magnetite, Fe ₃ O ₄ ) and maghemite (maghemite, γ-Fe ₂ O ₃ ) are preferable from the viewpoint that a high residual magnetization can be retained by the magnetization treatment.

  It is desirable that these magnetic materials have a residual magnetization of at least 0.003 emu or more due to the magnetization treatment. The magnetic material having such residual magnetization can be accurately detected by the TMR element 10. Examples of the magnetization treatment include a magnetization treatment with a permanent magnet and a magnetization treatment with an electromagnetic field. The magnetization direction is not particularly limited. Here, the lower limit of remanent magnetization is set to 0.003 emu, but this remanent magnetization is a value when 0.5 mg of magnetite is blended, and even such a remanent magnetization can be detected by the sensitivity of the TMR element or an amplifying means. It is possible. The remanent magnetization at this time is a value measured by a vibrating sample magnetometer (for example, VSM-5 manufactured by Toei Industry Co., Ltd. as described later), and emu is a unit of CGS-Gauss system.

  Even if the residual magnetization is at least 0.003 emu or more, or if the residual magnetization is small, for example, 0.01 emu or less, it is not easy to detect even if the TMR element 10 having high sensitivity is adopted. In such a case, it is necessary to detect the signal by amplifying the signal with an amplifier circuit. Therefore, it is preferable that the residual magnetization is high. On the other hand, in order to increase the remanent magnetization, it is sufficient to increase the amount of the magnetic material, but since it is desired to avoid including a large amount of the magnetic material in the composition for oral administration, the minimum amount detectable by the TMR element 10 is required. It is desirable to include the above magnetic material in the composition for oral administration. Therefore, in consideration of the magnitude of the residual magnetization that the magnetic material can have by the magnetization treatment, the amount of the magnetic material that can be contained in the composition for oral administration, the sensitivity of the TMR element 10, the amplifier circuit, and the like. , It is desirable to select and adjust each. The TMR element 10 may be a general-purpose TMR element that is easily available or a high-sensitivity TMR element as long as it can be detected by the residual magnetization of a magnetic material or an amplifier circuit. As will be shown by the results described later, the residual magnetization of the magnetic material is preferably 0.2 emu or more, which makes it easier to detect with the TMR element.

  The magnetic material may be in the form of powder, granules or pellets. In the case of a powder form, it is desirable that the average particle size be in the range of 1 to 100 μm, but it is not particularly limited. The average particle size can be evaluated by the average value of a plurality of values measured by a laser diffraction type particle size distribution meter, observation with a microscope, or the like.

  The aspect in which the magnetic material is included in the composition for oral administration 20 is not particularly limited, but for example, (1) the composition 20 for oral administration may contain a magnetic material as a core tablet, or (2) oral administration. The magnetic material may be coated so as to cover the surface of the composition 20 for oral use, or (3) the magnetic material may be printed on at least one surface of the composition 20 for oral administration. The magnetic material can be contained in one or more modes selected from these. According to such an aspect, the composition for oral administration can be included in various forms in consideration of the magnetization characteristics of the magnetic material.

  FIG. 2 is an example of an embodiment in which a magnetic material is included in a composition for oral administration. FIG. 2A shows a core tablet type magnetic material contained in a circular tablet type composition for oral administration (in a circular plain tablet). FIG. 2B shows a core tablet type magnetic material contained in an oval tablet type composition for oral administration (in a bar-shaped uncoated tablet). FIG. 2 (C) shows a core tablet type magnetic material having a smaller diameter contained in a circular tablet type composition for oral administration (in a circular core tablet). FIG. 2D shows a core tablet type magnetic material having a smaller diameter contained in an oval tablet type composition for oral administration (in a rod-shaped core tablet). FIG. 2 (E) shows a circular tablet type composition for oral administration, which is coated with a magnetic material so as to entirely cover the composition. FIG. 2 (F) shows a magnetic material coated so as to cover the entire oval tablet type composition for oral administration. FIG. 2 (G) is a circular tablet-shaped composition for oral administration in which a magnetic material is circularly printed on one side. FIG. 2 (H) shows a circular tablet type composition for oral administration in which a magnetic material is printed in a stick shape on one side. In these examples, the main component material 208 mg consisting of lactose hydrate, low-substituted hydroxypropyl cellulose, magnesium stearate, hypromellose, polyethylene glycol, talc, and titanium oxide was used. It is contained in the form of. The circular tablet has a diameter of 8 mm and a thickness of 3.5 mm, and the oval tablet has a major axis of 12 mm, a minor axis of 6 mm and a thickness of 3 mm.

  FIG. 3 shows the measurement results of the residual magnetization when the composition for oral administration contains the magnetic material (1.5 g of magnetite particles) in the forms of FIGS. 2 (A) to (H). The measurement is the result of measurement by a vibrating sample magnetometer (for example, VSM-5 manufactured by Toei Industry Co., Ltd.). When the kind and the blending amount of the magnetic material were the same, as shown in FIGS. 2C and 2D, the magnetic material contained in the tablet as a core having a smaller diameter showed a large residual magnetization. From this result, it is considered that the distance / contact point between the magnetic particles is increased and the synergistic effect of increasing the residual magnetization is produced by compressing and molding the magnetic material composed of the magnetic particles to reduce the diameter.

  FIG. 4 shows the relationship between the type of magnetic material and remanent magnetization, and FIG. 5 shows the relationship between the blending amount of magnetic material and remanent magnetization. From these relationships, the remanent magnetization of magnetite treated with metaphosphoric acid was about twice that of magnetite, and the remanent magnetization of maghemite was about 10 times that of magnetite. The remanent magnetization of magnetite and maghemite was proportional to the blended amount. There was no significant difference due to the aspect ratio (circular shape and rod shape).

[TMR element]
The TMR element 10 is not particularly limited, and spatially captures the magnetic field generated from the composition for oral administration to be detected in the measurement target site, detects the change in the captured magnetic field as an angle change in magnetization, and then changes the angle. It is possible to apply a TMR element capable of realizing the principle of reading as a change in resistance (change in current) by the TMR effect. The type of TMR element is not particularly limited as long as it can perform such detection, and it may be a high-spec TMR element with high measurement sensitivity, or a TMR element marketed for consumer use for various purposes. May be As an example of the TMR element 10, as shown in FIG. 6, a ferromagnetic metal magnetization fixed layer (referred to as a magnetization fixed layer) 11, an insulating layer 13, and a ferromagnetic metal magnetization free layer (referred to as a magnetization free layer) 12 are provided. And have. The resistance of the TMR element 10 changes according to the relative angle between the magnetization of the magnetization fixed layer 11 and the magnetization of the magnetization free layer 12. The magnetic material forming the magnetization fixed layer 11 and the magnetization free layer 12 is not particularly limited, and examples thereof include CoFeB alloy, CoFe alloy, CoFeNi alloy, and CoFeNiB alloy. In addition, as the insulating layer 13, MgO or the like can be preferably mentioned, and a high magnetoresistive ratio can be obtained.

  In the TMR element 10, as shown in FIG. 6, it is preferable that one or both of the magnetization free layer 12 and the magnetization fixed layer 11 be an antiparallel coupling film structure 15. The TMR element 10 including the antiparallel coupling film structure 15 spatially captures the magnetic field generated from the composition 20 for oral administration to be detected in the measurement target site 50, and changes the captured magnetic field to change the angle of magnetization. Since the angle change can be detected as a change in resistance (change in current) by the TMR effect, the present invention can be preferably applied.

  The antiparallel coupling film structure 15 is an ultrathin film sandwiched between the first ferromagnetic layer 15a, the second ferromagnetic layer 15b, and the first ferromagnetic layer 15a and the second ferromagnetic layer 15b. It has a non-magnetic layer 15c. The magnetization of the first ferromagnetic layer 15a and the magnetization of the second ferromagnetic layer 15b have exchange coupling forces that are antiparallel to each other. The first ferromagnetic layer 15a and the second ferromagnetic layer 15b are not particularly limited, and a magnetic material that can achieve the effects of the present invention can be adopted. In the antiparallel coupling film structure 15, exchange interaction acts on the magnetizations of the two ferromagnetic layers 15a and 15b depending on the film thickness of the ultrathin nonmagnetic layer 15c, and the magnetizations of the two ferromagnetic layers 15a and 15b become antiparallel at a certain film thickness. Tightly bond to face.

  As an example of the antiparallel coupling film structure 15, one of the first ferromagnetic layer 15a and the second ferromagnetic layer 15b is a CoFeB alloy or a CoFe alloy, and the other is a CoFe alloy or a NiFe alloy having a face-centered cubic structure. Can be The ultrathin nonmagnetic layer 15c may be a Ru layer or the like, and the thickness thereof is preferably about 0.8 nm. Incidentally, the CoFe alloy or the NiFe alloy is usually formed via the underlayer. As the underlayer, a laminated film of Ta / Ru or the like can be preferably mentioned.

  Each of these layers can be formed on a substrate provided with a thermal oxide film by various film forming means such as ultra-high vacuum sputtering. Further, it is preferable that the heat treatment is performed at about 300 ° C., if necessary. By heat treatment at a temperature within this range, the antiparallel coupling film structure 15 having high antiparallel coupling strength can be manufactured. As a substrate on which each of these layers is provided, a silicon substrate, a quartz substrate, or the like, which has heat resistance and etching resistance, can be mentioned. A silicon substrate or a quartz substrate is excellent in a film forming process and heat resistance, and thus is preferably applicable.

(Operation of TMR element)
The TMR element 10 oscillates in one or more directions selected from the front-rear direction, the left-right direction, the up-down direction, and the oblique direction with respect to the composition 20 for oral administration in the digestive tract. By doing so, the magnetic material contained in the orally administrable composition 20 can be detected by oscillating the TMR element 10 even when the orally administrable composition 20 is in a static or substantially stationary state in the digestive tract. it can.

  The amplitude direction (also referred to as the swinging direction) of the TMR element 10 is not particularly limited as long as it is the above-described directions or a combination thereof. The detection signal obtained by oscillating the TMR element 10 is affected to a large extent by the magnetic field formed by the magnetic material contained in the composition for oral administration, but the magnitude of the residual magnetization of the magnetic material, the sensitivity of the TMR element, and the amplitude. The influence can be minimized by adjusting the direction, the magnitude of the amplitude, and the like.

  The magnitude of the amplitude depends on the performance of the TMR element 10 and the magnitude of the residual magnetization of the magnetic material, and is not particularly limited. However, it is preferable that the magnitude is 2 mm or more and 5 mm or less in each direction. By doing so, a large signal can be detected, and noise generated by vibration or movement of wiring can be suppressed small. The front-back direction is a direction that approaches or leaves the orally-administered composition 20 that is the detection target, and the left-right direction, the up-down direction, and the diagonal direction are the directions of the oral-administration composition 20 that is the detection target. The distance is in the direction of oscillating in a substantially constant manner. If the amplitude is less than 2 mm, it can be detected by using the highly sensitive TMR element 10, but it is slightly difficult in terms of cost. On the other hand, the amplitude may exceed 5 mm, which makes detection easier, but the device becomes slightly larger. Therefore, it is preferably about 5 mm or less if possible.

  The frequency of the amplitude (referred to as vibration frequency) also depends on the performance of the TMR element 10 and the magnitude of the residual magnetization of the magnetic material and is not particularly limited, but the vibration frequency is preferably within the range of 1 to 200 Hz. More preferably, it is within the range of 1 to 20 Hz. At the time of measurement, noise such as external noise or internal noise generated from an electric circuit, a motor, or the like may exist. Therefore, it is preferable that the frequency of the amplitude is in a frequency range that is not easily affected by such noise. From the viewpoint, it is more preferably within the range of 1 to 20 Hz described above. By doing so, it is possible to avoid overlapping with noise, and it is possible to detect that the composition for oral administration is being taken or ingested, with the influence of noise being suppressed as much as possible. It should be noted that when the vibration frequency is set to 10 Hz or higher, the low frequency noise tends to increase, and it is slightly difficult to detect, but even in that case, if the frequency noise is different from the vibration frequency, digital filtering is performed. It was confirmed that the noise can be removed by the processing.

(Structure form)
The composition detecting apparatus 1 for oral administration shown in FIG. 1 includes various main parts other than the TMR element 10 as required. Examples of the main parts include a transmitting means, a battery, a circuit, a microcomputer, and the like. By doing so, since the detection result of the TMR element 10 can be transmitted, it can be detected that the composition for oral administration has been taken even at a distant place, and by outputting the detection information, it is possible to notify other than the patient. , A family member, a doctor, a nurse, a caregiver, etc. can confirm the composition for oral administration. Furthermore, it is preferable to combine it with a receiver such as a smartphone that receives a signal from the composition detecting device 1 for oral administration.

  These components function so that the current output from the TMR element 10 is amplified or noise-cancelled as necessary, output to a microcomputer, and transmitted to a display device, an analysis device, or the like by wire or wirelessly. .. The transmission means may be wired transmission using a signal line, or short-distance communication means using Bluetooth (registered trademark) used in mobile communication.

  Further, the orally administered composition detecting device 1 may be optionally combined with other sensor devices such as a GPS sensor, a pressure sensor, a heartbeat sensor and a vibration sensor. Combined with such a sensor, it is possible to detect various information (for example, behavior records of dementia patients, seizure records of epilepsy patients, signs of seizures of epilepsy patients, etc.), and realize comprehensive analysis. It becomes possible to do it.

  As shown in FIG. 1, the orally-administered composition detecting apparatus 1 has a predetermined position on the torso so that the orally-administered composition detecting apparatus 1 can detect the orally-administered composition 20 while being taken or ingested in the stomach or intestines. It is desirable to be placed at 51 and used. It may be arranged at another position, for example, on the esophagus, or may be detected when the composition 20 for oral administration passes through the esophagus.

  The present invention will be described in more detail by the following experiments.

[Experiment 1]
In Experiment 1, a passage test of a tablet sample in a rubber tube was conducted. In this experiment, the rubber tube was simulated as a human digestive system. As the detection device 1, a 100 dB sensor module manufactured by Radix Co., Ltd. was used. This sensor module employs a commercially available TMR element with a sensitivity specification of 10 nT / LSB, amplifies the signal measured by the TMR element, inputs it to a filter circuit, and digitizes it with an A / D converter for personalization. Recorded by computer. At this time, the amplification factor of the amplifier circuit was 100 dB, and the filter circuit was set under conditions of a high-pass filter 0.1 kHz, a low-pass filter 0.1 Hz, and a notch filter 50 Hz. As a tablet sample, a 1.5 mg magnetite-containing film-coated tablet (outer diameter: 8 mm) and a 1.5 mg maghemite-containing film-coated tablet (outer diameter: 8 mm) were used. The diameter of the rubber tube was about 4 cm, and the rubber tube was arranged so that the distance between the detection device 1 and the tablet was about 2 cm. In the measurement, the magnetic characteristics detected by the detection device 1 when the tablet sample was dropped in the rubber tube were measured with an oscilloscope (DCS-2072E, Texas Technology Corporation).

  FIG. 7 shows the results of a detection experiment with the detection device 1 when the tablet sample passes through the rubber tube, (A) shows the case of the magnetite-containing film-coated tablet, and (B) shows the maghemite-containing film-coated tablet. This is the case. According to this experiment, the tablet sample containing the magnetic material could be detected by the detection device 1. Particularly, the tablet sample used in FIG. 7 (B) was able to obtain favorable results.

[Experiment 2]
In Experiment 2, a confirmation experiment in humans was performed. The same detector 1 as used in Experiment 1 was used. As a tablet sample, a film-coated tablet containing 40 mg maghemite (outer diameter: 8 mm) was used. The first detection device 1 was attached to the neck position, and the second detection device 1 was attached to the stomach position. The distance between the detection device 1 and the tablet was set to about 5 to 10 cm. The measurement was performed in the same manner as in Experiment 1.

  FIG. 8 shows the detection results when the tablet sample was ingested, (A) shows the results when the detecting device 1 was installed at the neck position, and (B) shows the detecting device 1 installed at the stomach position. This is the result of the case. As shown in FIG. 8 (A), a magnetic signal (circled in FIG. 8 (A)) was detected even before swallowing, and erroneous detection was feared due to disturbance. Further, as shown in FIG. 8 (B), the magnetic signal (circle in FIG. 8 (B)) could be detected at the moment of entering the stomach, but the output of magnetic characteristics was stable in the stomach. I found out not.

  From the results of Experiments 1 and 2, the magnetic properties when the tablet sample moved can be detected, but the results when the tablet sample was actually swallowed were insufficient. It was found that the detection at the neck position and the detection at the stomach position were both instantaneous signals, and it was difficult to distinguish them from disturbance. If we were to catch a momentary change, it would be necessary to constantly monitor, and it was expected that the measurement would be complicated.

[Experiment 3]
Based on the results of Experiments 1 and 2 described above, it was considered that detection was difficult because the tablet did not move in the stomach. Therefore, in this experiment, an experiment in which the detection device 1 installed outside the body was moved was performed. went. By doing so, it is possible to expect long-term magnetic transmission from the tablet sample, and it was considered that measurement in the stomach, which exists for a long time, is particularly desirable.

  In Experiment 3, a vibration experiment of the detection device 1 was performed. In the vibration experiment, a 60 dB sensor module manufactured by Radix Co., Ltd. was used as the detection device 1. This sensor module also employs a commercially available TMR element having a sensitivity specification of 10 nT / LSB, amplifies the signal measured by the TMR element, converts it into digital data by an A / D converter, and records it in a personal computer. The amplification factor of the amplifier circuit at this time was set to 60 dB, but the filter circuit as in Experiment 1 was not set. The detection device 1 was vibrated at an amplitude of 1 mm and a frequency of 0.33 to 13.33 Hz. As a tablet sample, a film-coated tablet containing 40 mg of maghemite (outer diameter: 8 mm) was used. The distance between the detection device 1 and the tablet was 2.5 cm. The measurement was performed by vibrating the detection device 1 for 20 seconds without the tablet, and then with the tablet for 20 seconds, and the magnetic characteristics detected by the detection device 1 at that time were sampled with an oscilloscope (DCS-2072E, Texas Technology Corporation) at a sampling cycle. It was measured at 500 Hz.

  FIG. 9 shows the results when the detection device 1 was vibrated at 3 Hz to 13.33 Hz. Only when there was a tablet (after 20 seconds), an AC signal corresponding to the frequency was obtained. In this experiment, low frequency noise was generated when the vibration frequency exceeded 8 Hz. FIG. 10 shows the result of FIG. 9 after the average value is zero-corrected and the band-pass filter process is performed. By such digital filtering processing, noise could be considerably removed.

  According to the result of Experiment 3, good detection could be realized at a vibration frequency of the detection device 1 of about 2 to 10 Hz. When the vibration frequency was too high, the noise increased and the detection power decreased, but it was found that the detection power can be improved by the digital filtering process.

[Experiment 4]
Further, an amplitude experiment of the detector 1 was conducted. In the amplitude experiment, the same 60 dB sensor module as in Experiment 3 was used as the detection device 1. The detection device 1 was vibrated at an amplitude of 1 to 4 mm and a frequency of 0.67 Hz. As a tablet sample, a film-coated tablet containing 40 mg of maghemite (outer diameter: 8 mm) was used. The distance between the detection device 1 and the tablet was 3 cm. For the measurement, the detection apparatus 1 was vibrated for 20 seconds without the tablet, and then vibrated for 20 seconds with the tablet. The measurement was performed in the same manner as in Experiment 2.

  FIG. 11A shows the result when the detection device 1 is oscillated at 1 mm to 4 mm. FIG. 11B shows the result after the average value is zero-corrected and the bandpass filter process is performed.

  From these results, as an influence of the vibration frequency, it is possible to detect an AC signal corresponding to the frequency only when there is a tablet, and in this experimental system, the low frequency noise becomes large when the vibration frequency is 8 Hz or more, and the detection power A drop was confirmed. Low-frequency noise could be removed to some extent by digital filtering (bandpass filter). As for the influence of the amplitude, it was possible to increase the AC signal by increasing the amplitude. Regarding the relation between the vibration frequency and the amplitude, it was found that the larger the amplitude, the larger the signal, but the lower the frequency limit at which noise is generated. Therefore, in the present experimental system, there is not much merit to increase the frequency, and the vibration at the low frequency with the amplitude of 2 to 3 mm was optimal. The orientation of the TMR element was also confirmed, but no significant difference was observed. The vibration direction was also confirmed, but it was confirmed that the fluctuation pattern of the DC / AC signal varied depending on the tablet angle in the vibration direction. It was also found that there are blind spots where tablets cannot be detected, and it is necessary to install a combination of DC / AC signals and a plurality of sensors having different vibration directions and positions to eliminate detection omissions.

[Experiment 5]
In Experiment 5, the magnetic field distribution generated from the tablet sample was quantitatively investigated, and when it was assumed that it existed in the stomach, basic data for determining whether or not measurement was possible from outside the body using the detection device 1 was acquired. It was done. HMMT-6Jxx-VR (product name) manufactured by Toyo Technica Co., Ltd. was used as a magnetic probe, and Model 425 (product name) manufactured by Toyo Technica Co., Ltd. was used as a gauss meter. The detection device 1 and the tablet sample used were the same as those used in Experiment 1. The three-dimensional magnetic field distribution generated from the tablet sample was measured with a Gauss meter (including a magnetic probe and a Gauss meter; the same applies hereinafter). In the measurement, the tablet sample was fixed to the magnetic field distribution measurement base in the magnetically shielded room, and at all points where the measurement points of each axis on the base and the spacer intersected, a Gauss meter was used to measure the (x, y, z) direction. The magnetic field was measured and the three-dimensional distribution was measured. As a premise, the magnetic field distribution generated from the tablet sample is ideal, and in a three-dimensional space with the center of the tablet sample as the origin, z = 0 xy plane, x = 0 yz plane, and y = The x-z plane of 0 is a symmetry plane. The magnetic probe used for the measurement was used by inserting it into a pipe made of non-magnetic material made of aluminum and having an outer diameter of 12 mm so that the angle can be easily changed in 90 ° units with good reproducibility.

  FIG. 12 shows the magnetic field intensity x at y = 0.0 mm and z = 0.0 mm in order to determine whether the magnetic field generated from the tablet sample used this time can be measured from outside the body using the detection device 1. It is the result of fitting by the inverse distance damping and the direction distance dependency. When the distance dependence of the magnetic field strength was predicted by performing such fitting, it was about 0.04 μT at 500 mm and about 0.01 μT at 1000 mm. Considering that the sensitivity of the TMR element constituting the detection device 1 at 0.1 to 10 Hz is about 0.002 μT, the magnetic field strength and the sensor sensitivity are at a level sufficient to measure tablets from outside the human body. Presumed.

DESCRIPTION OF SYMBOLS 1 Composition detection device for oral administration 10 TMR element 11 Ferromagnetic magnetization fixed layer 12 Ferromagnetic magnetization free layer 13 Insulating layer 15 Antiparallel coupling film structure 15a 1st ferromagnetic layer 15b 2nd ferromagnetic layer 15c Ultrathin Non-magnetic layer 20 Composition for oral administration 21 Magnetic material 22 Composition material 50 Measurement target site 51 TMR element placement position

Claims (12)

  A composition for oral administration containing a magnetic material that can be detected by a magnetoresistive effect element placed outside the body.   The composition for oral administration according to claim 1, wherein the magnetic material is iron oxide.   The composition for oral administration according to claim 1, wherein the magnetic material is magnetite or maghemite.   The composition for oral administration according to claim 1, wherein the magnetic material is magnetized.   The composition for oral administration is a drug, a health food, a functional food, a dietary supplement, a supplement, a food with health claims, a food for specified health uses, a nutritionally functional food, or a functionally labeled food. A composition for oral administration.   One or more selected from the group consisting of the magnetic material contained in the composition for oral administration, covering the surface of the composition for oral administration, and printed on the surface of the composition for oral administration. The composition for oral administration according to claim 1, which is:   The device for detecting the composition for oral administration according to claim 1, comprising a magnetoresistive effect element for detecting whether or not the composition for oral administration is present in the digestive tract, and the magnetoresistive effect element. The composition detection device for oral administration, which vibrates.   The said magnetoresistive effect element oscillates with respect to the composition for oral administration in the said digestive tract in 1 or 2 or more directions chosen from a front-back direction, a left-right direction, a vertical direction, and a diagonal direction. Composition detection device for oral administration.   The composition detecting device for oral administration according to claim 7, wherein the vibration frequency of the amplitude is within a range of 1 to 200 Hz.   The composition detecting device for oral administration according to claim 7, wherein the vibration frequency of the amplitude is within a range of 1 to 20 Hz.   The method for detecting the composition for oral administration according to claim 1, wherein the detection device equipped with a magnetoresistive effect element for detecting whether or not the composition for oral administration is present in the digestive tract. A method for detecting a composition for oral administration. The method for detecting a composition for oral administration according to claim 11, wherein one or two or more of the detection devices are installed at any position of a torso including a chest and an abdomen.