阅读说明：本技术 包装的药品 (Packaged pharmaceutical product ) 是由 横井一真 樫原健造 山本健太 园木贵博 山田昌平 于 2018-05-01 设计创作，主要内容包括：提供包装的药品,其能够在长时间内阻止电极的劣化,并且即使当从生产到摄取已经经过长时间时,也能够在摄取后可靠地发射信号。包装的药品包括：包括药品粉末和微型装置的固体药品；设有固体药品容纳空间的容器,固体药品容纳空间中容纳固体药品；以及被封装在固体药品容纳空间中的惰性气体。微型装置包括：具有彼此不同电离趋势的两个电极；以及发射器,使用当电极与电解质接触时产生的电动势来发射信号。(Provided is a packaged pharmaceutical product which can prevent degradation of an electrode for a long period of time and can reliably emit a signal after ingestion even when a long period of time has elapsed from production to ingestion. The packaged pharmaceutical product comprises: a solid drug comprising a drug powder and a microdevice; a container provided with a solid medicine accommodating space in which a solid medicine is accommodated; and an inert gas enclosed in the solid drug containment space. The micro device includes: two electrodes having different ionization tendencies from each other; and a transmitter which transmits a signal using an electromotive force generated when the electrode is in contact with the electrolyte.)

1. A packaged pharmaceutical product comprising:

a solid drug product comprising a drug powder and a micro device;

a container provided with a solid medicine containing space that contains the solid medicine therein; and

an inert gas encapsulated in the solid drug containment space;

the micro device includes:

a first electrode comprising a first material;

a second electrode comprising a second material having an ionization tendency different from that of the first material; and

a transmitter that transmits a signal using an electromotive force generated between the first electrode and the second electrode when the first electrode and the second electrode are in contact with an electrolyte.

2. The packaged pharmaceutical product of claim 1, wherein

The solid pharmaceutical product is a tablet, and

the micro device is supported by the tablet.

3. The packaged pharmaceutical product of claim 1, wherein

The solid medicine has a capsule, and

the drug powder and the micro device are contained in the capsule.

4. The packaged pharmaceutical product of claim 1, wherein

The solid medicine is provided with a capsule which is provided with a plurality of capsules,

the medicine powder is contained in the capsule, and

the micro device is held in the capsule.

5. The packaged pharmaceutical product of any one of claims 1 to 4, wherein the inert gas is nitrogen.

6. A packaged pharmaceutical product according to any one of claims 1 to 5, wherein the container is a blister pack, a sachet pack, a can pack or a bottle pack.

7. The packaged pharmaceutical product of any one of claims 1 to 6, wherein the first material is copper chloride.

8. The packaged pharmaceutical product of any one of claims 1 to 7, wherein the second material is magnesium.

9. A packaged pharmaceutical product according to any one of claims 1 to 8, wherein the pharmaceutical product powder is one whose quality is not deteriorated by contact with oxygen.

Technical Field

The present invention relates to a packaged pharmaceutical product, wherein a pharmaceutical product (e.g. a tablet or capsule) comprising a microdevice is packaged in a container.

Background

Patent documents 1 to 3 each disclose a tablet containing an embedded micro device (IC chip). The chip-in-tablet can be made by compressing a dose of a powdered drug containing the microdevice from above and below.

Patent document 4 discloses one of the tablets of the internal clamp micro-device, that is, a tablet having an emitter designed to emit a signal when the tablet is taken into the body and then comes into contact with a conductive liquid (e.g., gastric acid). In one embodiment disclosed in patent document 4, in order to form a chemical battery by using a conductive liquid in the body as an electrolyte, which generates electric power by the battery to emit a signal, the micro device has: a pair of anode and cathode electrodes having ionization tendencies different from each other; and a transmitter capable of transmitting a signal using the power generated between the electrodes. For example, in this example, copper chloride is used for the anode electrode, and magnesium, sodium zinc, or lithium iron is used for the cathode electrode.

Disclosure of Invention

Disadvantageously, the anode electrode made of copper chloride tends to deteriorate with time. In general, the deterioration of the anode has been considered to be caused by contact with other substances (particularly, moisture). Therefore, in order to ensure that the micro device fully exhibits its performance, it is considered necessary to place the micro device in a dry state by means of a desiccant.

Accordingly, the inventors of the present application have conducted extensive studies to provide a packaged drug which can prevent the degradation of its electrode for a long period of time and can reliably emit a signal regardless of the time from the production to the ingestion after being ingested, which indicates that the anode electrode is easily degraded once placed in the atmosphere, in particular, by being in contact with oxygen and moisture contained in the atmosphere (i.e., copper chloride (CuCl) forming the anode electrode of the microdevice and oxygen (O) in the surrounding atmosphere₂) And water (H)₂O) contact) to produce basic copper chloride (Cu2(OH)₃Cl) resulting in degradation of the anode electrode, which results in the micro device possibly failing to emit a desired signal when ingested. Based on the knowledge obtained from this study, the inventors found that isolating the tablet under low oxygen conditions can protect the tablet from oxygen and thereby prevent the tablet from deteriorating even after a long period of time has elapsed from the start of production, and thus completed the present invention.

In order to achieve the above object, a packaged medicine according to the present embodiment includes:

a solid drug product comprising a drug powder and a micro device;

a container provided with a solid medicine containing space that contains the solid medicine therein; and

an inert gas encapsulated in the solid drug containment space;

the micro device includes:

a first electrode comprising a first material;

a second electrode comprising a second material having an ionization tendency different from that of the first material; and

a transmitter that transmits a signal using an electromotive force generated between the first electrode and the second electrode when the first electrode and the second electrode are in contact with an electrolyte.

In another form of the invention, the solid pharmaceutical product is a tablet and the microdevice is supported by the tablet.

In another aspect of the present invention, the solid medicine has a capsule, and the medicine powder and the microdevice are contained in the capsule.

In another aspect of the present invention, the solid medicine has a capsule in which the medicine powder is contained, and the microdevice is held in the capsule.

In another form of the invention, the inert gas is nitrogen.

In another form of the invention, the container is a blister pack, a sachet pack, a can pack or a bottle pack.

In another aspect of the present invention, the first material is copper chloride.

In another aspect of the invention, the second material is magnesium.

In another form of the present invention, the medicine powder is a medicine powder whose quality is not deteriorated even when it comes into contact with oxygen.

According to the embodiment of the present invention configured in this way, since the tablet placed in an environment with a low concentration of oxygen is isolated from oxygen and prevented from deteriorating, the tablet can emit a signal in a stable manner by entering the body and coming into contact with body fluid (gastric acid) even when the tablet is not taken until a long period of time has elapsed from the start of production.

Drawings

FIG. 1 is a perspective view of a packaged pharmaceutical product according to one embodiment of the present invention;

FIG. 2 is a perspective view of a tablet included in the packaged pharmaceutical product shown in FIG. 1;

FIG. 3 is a block circuit diagram of a micro device mounted in the tablet shown in FIG. 2;

FIG. 4 is a graph showing the results of experiment 1;

FIG. 5 is a graph showing the results of experiment 2;

FIG. 6 is a graph showing the results of experiment 3;

FIG. 7 is a graph showing the results of experiment 4;

fig. 8 is a perspective view of a packaged pharmaceutical product according to another embodiment.

Detailed Description

Hereinafter, embodiments of a packaged pharmaceutical product according to the present invention will be described with reference to the accompanying drawings.

Fig. 1 shows a packaged pharmaceutical product 10 according to an embodiment of the invention. The illustrated packaged pharmaceutical product 10 has a blister pack (container) 12 or blister pack sheet. For example, blister pack 12 is made by bonding together transparent plastic sheets 14 and aluminum sheets 16 that form respective upper and lower layers of the packaged pharmaceutical product. The upper transparent plastic sheet 14 includes a plurality of medicine-containing chambers (medicine-containing chambers) 18 for containing medicines, the plurality of medicine-containing chambers 18 being formed, for example, by vacuum forming, each of the plurality of medicine-containing chambers 18 having a configuration matching the contained medicine. The bottom opening of the medicine-containing chamber 18 is sealed by the lower aluminum sheet 16.

Each of the plurality of medication-containing compartments 18 of the blister pack 12 contains a solid medication 20. In this embodiment, the solid pharmaceutical product 20 is a tablet 22. Although the size of the tablet 22 is not limited, the maximum size of the medicine is preferably 5mm to 12mm, and more preferably 7mm to 8mm, in view of easy ingestion.

The air in medicine-containing compartment 18 is replaced with an inert gas during production of the packaged medicine so that tablet 22 is placed in an environment with a low concentration of oxygen. Although the substitution rate of the inert gas is not necessarily 100%, it is advantageous that the proportion of the remaining oxygen in the medicine-containing chamber 18 is as low as possible. Preferably, nitrogen is used as the inert gas, but other inert gas substitutions may be used.

A method of replacing the air in the medicine-containing chamber 18 of the blister pack 12 with an inert gas is well known, for example, in JP2011-213351 a.

As shown in fig. 2, the tablet 22 holds a micro device (microchip) 24. The maximum size of the micro device 24 is 1mm or less, and preferably several tens to several hundreds of micrometers.

In this embodiment, the micro device 24 is held within the tablet 22. As described in patent documents 1 to 3, a tablet holding a microdevice inside in this way is formed by compressing a medicine powder and a microdevice arranged therein from above and below. The tablet 22 may be a tablet made of a medicine powder that does not cause deterioration in quality due to contact with oxygen. The "pharmaceutical powder without deterioration in quality" means that the content of the pharmaceutical powder decreases by 5% or less, the content of the analogous substance increases by 1.0% or less, or the elution decreases by 10% or less during storage at a temperature of 25 ℃ for 36 months or a temperature of 40 ℃ for 6 months.

The micro device 24 may be attached to the surface of the tablet 22. In this embodiment, the micro devices 24 are preferably attached to the surface of the tablet using a suitable edible adhesive (e.g., starch glue).

As shown in fig. 3, the micro device 24 is made of a semiconductor integrated circuit substrate (silicon substrate) 26, in which an anode electrode 28 and a cathode electrode 30 are mounted on the surface of the substrate. For example, the substrate 26 is manufactured using known semiconductor manufacturing techniques, and the anode electrode 28 and the cathode electrode 30 are produced using known film forming techniques. In this embodiment, copper chloride is used for the anode electrode 28, and magnesium is used for the cathode electrode 30.

Various circuits are formed on the substrate of the micro device 24. For example, the micro device 24 according to the embodiment includes a power supply unit (power supply circuit) 32, a control unit (control circuit) 34, and a transmitter (transmission circuit) 36. The power supply unit 32 is configured to be connected to the anode electrode 28 and the cathode electrode 30, either directly or indirectly, such that when the microdevice 24 is contacted with a conductive body fluid (e.g., stomach acid), the power supply unit 32 cooperates with the anode electrode 28 and the cathode electrode 30 to form a chemical cell, the power supply unit 32 supplying electrical energy to other circuitry. The control unit 34 is configured to receive power supplied from the power supply unit 32 and transmit a signal to the transmitter 36. The transmitter 36 is configured to receive power from the power supply unit 32 and transmit signals in response to signals from the control unit 34.

According to the packaged medicine 10 thus constructed, the tablet 22 is contained in the medicine accommodating chamber 18 substantially filled with an inert gas and insulated from moisture and oxygen. Therefore, even when a long period of time has elapsed from the start of production, the surface of the electrode (particularly, the anode electrode made of copper chloride) of the microdevice 24 does not generate a basic copper chloride portion. In addition, when the tablet 22 is ingested into the body of a patient and then comes into contact with gastric acid, the anode electrode 28 and the cathode electrode 30 form a chemical cell together with gastric acid to generate electromotive force. The generated power is supplied from the power supply unit 32 to the control unit 34 and the transmitter 36. The transmitter 36 transmits a signal in response to a signal from the control unit 34. The transmitted signal is received by a patient's dedicated receiver or computer capable of receiving the signal (e.g., a smart phone) which is equipped with dedicated software or application that records the manner of administration of the tablet.

Experiment of

The micro device is placed in different environments, and the life (signal generation time) of the micro device is measured.

[ experiment 1]

The prepared blister pack had a pair of opposing aluminum cover sheets and a tablet (a) with a built-in micro device disposed between the cover sheets. The blister pack was placed in an experimental environment at a temperature of 60 c, oxygen concentrations of 20.9%, 5% and 1%. After zero weeks (0W) (i.e., immediately after being placed in the experimental environment), 1 week (1W), 2 weeks (2W), 3 weeks (3W), 4 weeks (4W), 6 weeks (6W), and 12 weeks (12W), the tablets were removed from each experimental environment. The tablets were then contacted with the test solution to measure the signal emission time. In addition, the water content (%) of the tablet at each elapsed time [ (mass of water contained in the tablet/mass of medicine) × 100] was measured. The results of this experiment are shown in fig. 4A and 4B. In fig. 4A, the vertical axis represents the transmission time, and the horizontal axis represents the elapsed time. In fig. 4B, the vertical axis represents water content, and the horizontal axis represents a measurement time point.

[ experiment 2]

A blister pack containing tablet B was prepared. Other experimental conditions were the same as those of experiment 1. The results of this experiment are shown in fig. 5A and 5B.

[ experiments 3 and 4]

Two types of double-sided aluminum blister packs were prepared for tablets a and B, each with a built-in microdevice. These blister packs were placed in the experimental environment at a temperature of 40 ℃ and oxygen concentrations of 20.9%, 5% and 1%. After zero weeks (0M) (i.e. immediately after placement in the experimental environment), 1 month (1M), 3 months (3M), 6 months (6M), tablets were removed from each experimental environment. The tablets were then contacted with the test solution to measure the signal emission time. The results of experiment 3 and experiment 4 for tablet (a) and tablet (B) are shown in fig. 6A and 6B and fig. 7A and 7B, respectively.

Fig. 4B, 5B, 6B, and 7B show that the concentration of oxygen in the package does not affect the amount of moisture contained in the tablet. In addition, fig. 4A, 5A, 6A, and 7A show that although the performance of the micro device is not significantly reduced in the environment with a low oxygen concentration (5% and 1%), the performance of the micro device is significantly reduced at an early stage (1W to 2W) in the environment with a high oxygen concentration (20.9%).

As described above, experiments prove that the oxygen concentration in the environment significantly affects the deterioration of the performance of the micro device. Therefore, according to the embodiments of the present invention described above, a tablet that is placed in an environment with a low concentration of oxygen for a long time from production to ingestion can also emit a signal in a stable manner by coming into contact with a body fluid.

Although the discussion has been made with respect to a specific embodiment in which the solid pharmaceutical product 40 of the packaged pharmaceutical products is a tablet, the pharmaceutical product may be a capsule 42 as shown in fig. 8. In this embodiment, the microdevice may be loosely packed with the powdered drug in the receptacle 44 of the capsule.

Alternatively, the micro device may be secured to an inner or outer surface of the container 44. In this embodiment, it is preferable that each electrode, particularly the anode electrode made of copper chloride which is easily deteriorated, is bonded and protected so that the electrode does not directly contact with the air.

Although in the foregoing embodiments the container of the packaged medicine is made of a blister pack having a top aluminum sheet and a bottom aluminum sheet, the container may be a laminated container made by bonding a top plastic sheet and a bottom aluminum sheet together.

Further, the container for containing the solid medicine is not limited to a blister pack, and may be a pouch pack, a can pack, or a bottle pack.

Reference numerals

10 pack pharmaceutical product

12 blister package

14 plastic sheet

16 aluminium sheet

18 medicine room (medicine containing space)

20 solid medicine

22 tablet formulation

24 micro device

26 base plate

28 anode electrode

30 cathode electrode

32 power supply unit

34 control unit

36 emitter

40 solid medicine

42 capsule

44 container