CN101259301A - Digital Pulse Release Electronic Capsule - Google Patents

Abstract

The digital pulse release electronic capsule relates to an oral drug delivery device. The digital pulse release electronic capsule of the present invention comprises a shell, a power supply, a start switch, a digital pulse generating circuit and an array type drug release device, and the array type drug release device includes a drug release driver array and a drug storage chamber array, and releases the drug The driver array includes a plurality of micro-drivers for drug release, and the drug storage bin array includes a plurality of micro drug storage bins. The digital pulse generation circuit generates pulse electrical signals of specific strength according to preset frequency and interval, and sends the pulse electrical signals according to a predetermined time sequence. Signals are respectively applied to each drug release micro-driver in the array type drug releaser to trigger the work of the drug release micro-driver to release the drug from the micro drug storage chamber. The invention provides an oral drug delivery device capable of setting a specific administration time according to individual differences of patients, capable of releasing drugs for multiple times, and not affected by individual differences of digestive tract environment.

Description

Digital Pulse Release Electronic Capsule

Technical field:

The invention relates to an oral drug delivery device, which is used for releasing substances, such as medicine, food, markers, etc., in the digestive tract of animals or humans.

Background technique:

In recent years, due to the development of chronobiology and chronopharmacology, it has been found that various physiological indicators of people, such as blood pressure, blood sugar, blood adrenal cortex hormone and other hormones, have a circadian rhythm. It also shows rhythmic characteristics, such as angina pectoris, gastric acid secretion, migraine, epilepsy, arthritis, and rheumatism. During the high-incidence period, the incidence of myocardial infarction also has a similar situation. On the other hand, studies have shown that the circadian rhythm of the disease also causes diurnal changes in the pharmacokinetics and pharmacodynamics of therapeutic drugs. For the treatment of the above-mentioned rhythmic diseases, ideal therapeutic drugs should meet the following conditions: (1) convenience. It is best to take the drug only once orally over a longer period of time, such as within 24 hours. (2) The drug can be released at a specific time point related to the law of the disease to obtain the best therapeutic effect, and the ability to release the drug multiple times at specific time intervals is a necessary technical requirement.

According to the existing technology, the sustained-release preparation can maintain a uniform and stable blood drug concentration for a long time, so that people can only take the drug once within a long period of time, such as within 24 hours, reducing the number of times of taking the drug and facilitating the daily life of patients. . However, sustained-release preparations cannot release drugs in pulses within a specific time period related to the law of the disease, and are less effective in treating regular diseases such as angina pectoris and asthma.

The current oral pulse preparation based on biomaterials can be dissolved after a preset time lag after entering the human body, and the time lag technology is used to respond to the patient's disease rhythm. However, although the current oral pulse drug delivery system already has a high time control accuracy, but the oral pulse drug delivery system based solely on biomaterial technology faces severe challenges of individual differences. time lag characteristics. The main reason is that there are individual differences in different patients, and the influencing factors include genetic factors, physiological factors, pathological factors, food structure, gastrointestinal micro-ecological environment, gastrointestinal motility characteristics, etc. There are different time lags in the body, so that it cannot accurately respond to the life rhythm of the patient's disease. (2) For the same disease, different patients have different life rhythms, so the curative effect of the same preparation in different patients is quite different. It is difficult for oral pulse preparations for mass production to accurately respond to life rhythms. There is an urgent need for a drug that can respond to patients Individual differences, an oral drug delivery system that can conveniently preset drug release time. For example, the level of catecholamines in the body of hypertensive patients increases when they wake up in the morning, which is the most likely to cause problems. Generally speaking, the best time for administration is around three o'clock in the morning. The time when the level increases varies greatly. In the use of pulse controlled release tablets developed according to this statistical law, some patients have increased the patient's tolerance to the drug due to the pulse release of the drug at the wrong time, and instead reduced the therapeutic effect of the drug. Effect. In the field of oral drug delivery systems, oral pulse preparations that are purely based on biomaterial technology and are oriented to mass production have the problems of being difficult to accurately respond to life rhythms and obvious individual differences. Under the development trend of personalized medicine (Personality Medicine), it has become a A pressing problem in oral drug delivery systems.

Invention content:

The purpose of the present invention is to overcome the deficiencies of the prior art and provide an oral drug delivery system that can set a specific time interval according to individual differences in patients, release drugs multiple times, control accurately, and not be affected by individual differences in the digestive tract environment .

Technical scheme of the present invention is as follows:

Digital pulse drug release electronic capsule, including housing, power supply, start switch, digital pulse generation circuit and array type drug release device, said array type drug release device includes a drug release driver array and a drug storage bin array, the drug release driver array Including N drug release micro-drivers, the drug storage bin array includes N miniature drug storage bins, where N is a natural number greater than or equal to 2 and less than 1000, each drug release micro-driver and a miniature drug storage bin constitute a micro drug release unit, the micro drug storage bin is used to package the drug to be released, and each drug release micro-driver has a circuit connection with the digital pulse generating circuit, and the digital pulse generating circuit generates a pulse electrical signal of a specific intensity according to a preset frequency and interval Predetermined timing applies pulse electrical signals to each drug releasing micro-driver in the array drug releaser and triggers the work of the drug releasing micro-driver to release the drug from the micro drug storage bin.

The micro-actuator for drug release in the array type drug release device can be a micro-chemical propeller, which includes an igniter, a propellant chamber, and a propellant, and the micro-medicine storage chamber includes a piston, and the piston It is encapsulated between the propellant chamber and the micro storage chamber. The drug release micro-driver in the described array type drug release device can also be a micro-mechanical propeller, which includes a micro-heating resistor, a micro-spring, a spring fixing bracket, and a spring fixing bracket and a micro-heating resistor through a low melting point. The adhesive is fixedly connected or is fixedly connected by a low-melting polymer wire, and the spring is in a compressed state. The micro-medicine storage bin includes a piston, and the piston is packaged between the spring fixing bracket and the micro-drug storage bin. The digital pulse generating circuit includes a micro-single-chip microcomputer or a micro-specific integrated circuit. The start switch is a magnetically controlled switch that is in a closed state under normal conditions.

Working process and principle of the present invention are:

The digital pulse drug release electronic capsule is loaded with the drug to be released. Before swallowing, the start switch of the digital pulse drug release electronic capsule is in the off state, and the digital pulse generation circuit is not connected to the power supply, and is in the shutdown state. After the digital pulse-release electronic capsule is swallowed and enters the digestive tract of the human body or animal body, since the start switch is closed, the digital pulse generation circuit works, and generates pulse electrical signals of specific intensity according to the preset frequency and interval, and according to the predetermined time sequence The pulse electrical signal is applied to each drug release micro-driver in the array drug releaser, triggering the drug release micro-driver to work, releasing the drug from the micro drug storage chamber, and the drug enters the blood circulation system through the digestive tract of the human body or animal. In this way, a specific and regular blood drug concentration is generated in the human body or animal body to achieve the predetermined therapeutic effect.

Compared with the prior art, the present invention has the following technical effects:

(1) It is possible to set the time interval for releasing the drug according to individual patient differences. The digital pulse drug release electronic capsule of the present invention includes a digital pulse generation circuit, which can control the time interval of drug release by setting pulse circuit signals at specific intervals according to the needs of the patient through circuit hardware or software settings. Individual variability in responding patients.

(2) The drug can be released multiple times. The present invention adopts an array type drug release device, which can release drugs multiple times, thereby realizing pulse drug release, and can release drugs multiple times according to the patient's disease rhythm to achieve the best curative effect.

(3) The control is accurate and not affected by individual differences in the digestive tract environment. Because the present invention uses the digitized pulse generating circuit enclosed in the capsule shell to control the time of drug release, besides the advantages of accurate control of the electronic circuit, it is not affected by individual differences in the environment of the digestive tract, avoiding the traditional use of pharmaceutical preparations. Disadvantages of obvious individual differences in properties such as degradation, dissolution, and disintegration in vivo.

Description of drawings:

Figure 1 is a schematic diagram of the composition of the digital pulse-release electronic capsule of the present invention.

Fig. 2 is an appearance view of the digital pulse-release electronic capsule with 4 micro drug storage chambers of the present invention.

Fig. 3 is an appearance view of the digital pulse-release electronic capsule with 9 micro drug storage chambers of the present invention.

Fig. 4 is an appearance view of the digital pulse-release drug capsule with 16 micro drug storage chambers of the present invention.

Fig. 5 is an appearance view of the digital pulse-release drug capsule with 25 micro drug storage chambers of the present invention.

Fig. 6 is a schematic diagram of the structure of the array drug releaser including the microchemical propulsion device of the present invention.

Fig. 7 is a schematic diagram of the drug release process (during release) of the arrayed drug releaser including the microchemical propulsion device of the present invention.

Fig. 8 is a schematic diagram of the drug release process (release completion) of the arrayed drug releaser including the microchemical propulsion device of the present invention.

Fig. 9 is a graph showing a generation process of a drug release pulse signal and a corresponding blood drug concentration curve of the digital pulse drug release electronic capsule including 4 micro drug storage chambers of the present invention.

Fig. 10 is a schematic structural view of the arrayed drug releaser including the micromechanical propeller of the present invention.

Fig. 11 is a schematic view of the structure of the array drug releaser including the micromechanical propeller of the present invention.

Fig. 12 is a schematic diagram of the drug release process (during release) of the array drug release device including the micromechanical propeller of the present invention.

Fig. 13 is a schematic diagram of the drug release process (release completion) of the array drug release device including the micromechanical propeller of the present invention.

Fig. 14 is an appearance view of the digital pulse-release drug capsule with 6 micro drug storage chambers of the present invention.

Fig. 15 is a graph showing a generation process of a drug release pulse signal and a corresponding blood drug concentration curve of the digital pulse drug release electronic capsule including 6 micro drug storage chambers of the present invention.

In Figures 1 to 15:

1-housing, 2-start switch, 3-power supply, 4-digital pulse generating circuit, 5-array drug release device,

6-drug release driver array, 7-drug storage bin array, 8-drug release driver, 9-micro drug storage bin,

10-microchemical propulsion, 11-igniter, 12-propellant chamber, 13-propellant, 14-piston,

15-Detachable sealing head, 16-Medicine to be released, 17-Micromechanical propeller, 18-Micro heating resistor,

19-micro spring, 20-spring fixing bracket, 21-low melting point polymer wire, 22-sealing film

Detailed ways:

Example 1:

The digitized pulse-release drug electronic capsule of this embodiment, as shown in Figure 1, includes a housing 1, a start switch 2, a power supply 3, a digital pulse generating circuit 4 and an array drug release device 5, and the array drug release device includes a Drug release driver array 6 and a drug storage bin array 7, the drug release driver array includes N drug release micro-drivers 8, the drug storage bin array includes N miniature drug storage bins 9, according to actual needs and process conditions, N can be A natural number greater than or equal to 2 and less than 1000. In this embodiment, the value of N is preferably N=4, 6, 9, 16, 25, as shown in Figure 2, Figure 14, Figure 3, Figure 4, and Figure 5 respectively shown.

Each drug release micro-driver 8 and a micro drug storage bin 9 constitute a micro drug release unit, the micro drug storage bin 9 is used to package the drug 16 to be released, each drug release micro driver 8 and the digital pulse generation circuit 4 have a circuit connection , the digitized pulse generating circuit 4 generates a pulse electric signal of a specific intensity according to a preset frequency and interval, and applies the pulse electric signal to each drug release micro-driver 8 in the array drug release device 5 respectively according to a predetermined time sequence and The micro-driver for drug release is triggered to work, and the drug is released from the micro drug storage bin 9 .

In this embodiment, the micro-actuator 8 for drug release is a micro-chemical propeller 10, as shown in FIG. 6 . The microchemical propellor 10 includes an igniter 11, a propellant chamber 12, and a propellant 13, and the described miniature drug storage bin 9 includes a piston 14, and the piston is packaged between the propellant bin 12 and the miniature drug storage bin 9. The other end of the drug storage bin 9 is a detachable sealing head 15, and the detachable sealing head 15 is generally made of medical plastic with good biocompatibility, such as silicon rubber, or other biodegradable biomaterials. Made, the friction force between the detachable sealing head 15 and the inner wall of the miniature drug storage bin 9 is generally between 0.2-5 Newton, which can ensure the sealing and can be detached under an appropriate propulsion force. The micro medicine storage bin 9 also includes a structure to prevent the piston from breaking away.

The processing technology of the microchemical propulsion device 10 can refer to the processing technology for the micro-nano micro-propulsion device, and its processing material can be carried out on the silicon base, and can also be carried out on the polymer or metal, wherein the micro-propellant can be Conventional chemical propellants. The igniter 11 in this embodiment can be a miniature heating resistor, and the pulse signal can be a pulse voltage signal, and the pulse voltage signal makes the temperature of the miniature heating resistor rise rapidly, thereby igniting the propellant, and the propellant drives the piston 14 to move forward , the pressure generated forces the detachable sealing head 15 to detach, and then the medicine is separated from the medicine storage chamber 9 and released. Its working process is shown in Figure 7 and Figure 8, wherein Figure 7 is a schematic diagram of the working process in which one of the drug release drivers is releasing medicine, and Figure 8 is a schematic diagram of one of the drug release drivers having completed the drug release process, and the to-be-released drug in the schematic diagram The medicine 16 is a liquid preparation, and may also be a powder preparation, or a microparticle preparation, or a tablet preparation during implementation.

The length of the digitized pulse-release electronic capsule of this embodiment is between 20-40 mm, and the diameter is between 6-15 mm. The preferred size is 28 mm in length and 10 mm in diameter. The capsule shell 1 is made of medical plastic, such as polycarbonate. The digitized pulse generating circuit in this embodiment includes a micro-single-chip microcomputer or a micro-ASIC, and the size of the single-chip microcomputer meets the size and energy consumption requirements of the capsule. The start switch is a magnetically controlled switch that is normally closed. Before the capsule is swallowed, the magnetically controlled switch is close to a permanent magnet. The circuit of the medicine electronic capsule is disconnected, and after swallowing, the magnetic control switch is closed, the circuit is turned on, and the digitized pulse generating circuit 4 starts to work.

Fig. 9 is a schematic diagram of a drug release pulse signal generation process and the corresponding blood drug concentration curve of the digital pulse drug release electronic capsule including 4 micro drug storage chambers in this embodiment. The digital pulse drug release electronic capsule sends out drug release pulse signals 6 hours, 12 hours, 18 hours, and 24 hours after swallowing. The drugs are released from different micro drug storage bins at the above time points. The channel enters the blood circulation system to generate a corresponding blood drug concentration curve, which produces four peak blood drug concentration in the intervals around 6 hours, 12 hours, 18 hours, and 24 hours after swallowing, so as to achieve specific therapeutic effects, such as As shown in Fig. 9, the corresponding blood drug concentration curve can be adjusted by adjusting the interval of the drug release pulse signal.

Example 2:

The digitalized pulse-release electronic capsule of this embodiment has a basic structure similar to that of Embodiment 1, as shown in Figure 1, including a housing 1, a start switch 2, a power supply 3, a digital pulse generating circuit 4, and an array drug releaser 5. The array drug release device includes a drug release driver array 6 and a drug storage bin array 7, the drug release driver array includes N drug release micro-drivers 8, and the drug storage bin array includes N micro drug storage bins 9, according to actual needs And technological condition permits, N can be the natural number greater than or equal to 2 and less than 1000, and in the present embodiment, the value of N is preferably N=4,6,9,16,25, respectively Fig. 2, Fig. 14, Figure 3, Figure 4, Figure 5.

Each drug release micro-driver 8 and a micro drug storage bin 9 constitute a micro drug release unit, the micro drug storage bin 9 is used to package the drug 16 to be released, each drug release micro driver 8 and the digital pulse generation circuit 4 have a circuit connection , the digitized pulse generating circuit 4 generates a pulse electric signal of a specific intensity according to a preset frequency and interval, and applies the pulse electric signal to each drug release micro-driver 8 in the array drug release device 5 respectively according to a predetermined time sequence and The micro-driver for drug release is triggered to work, and the drug is released from the micro drug storage bin 9 .

In this embodiment, the micro-actuator 8 for drug release is a micro-mechanical propeller 17, as shown in Fig. 10 and Fig. 11 . The micromechanical propeller 17 includes a micro-heating resistor 18, a micro-spring 19, and a spring fixing bracket 20. The spring fixing bracket 20 and the micro-heating resistor 18 are fixedly connected by a low-melting point adhesive or by a low-melting point polymer wire 21. The micro-spring 19 is in a compressed state, and the miniature medicine storage bin 9 includes a piston 14, the piston 14 is packaged between the spring fixing support 20 and the miniature medicine storage bin 9, and the sealing of the other end of the miniature medicine storage bin 9 can be the same as that in the embodiment The one in 1 is sealed by a detachable sealing head 15, or it can be sealed by a sealing film 22. The sealing film 22 is made of medical plastic or other polymers with good biocompatibility, and its thickness is between 0.05mm-0.3mm. between. The micro medicine storage bin 9 also includes a structure to prevent the piston from breaking away.

The machining process of the micro-mechanical thruster 10 can be performed by conventional precision micro-machining process. In this embodiment, the pulse signal generated by the digital pulse generating circuit 4 can be a pulse voltage signal, and the pulse voltage signal causes the temperature of the micro heating resistor 18 to rise rapidly, thereby softening the adhesive or fusing the low-melting polymer wire 21, which is in the The microspring 19 in the compressed state is released and drives the piston 14 to move forward, and the generated pressure forces the sealing membrane 22 to rupture, and then the medicine breaks away from the medicine storage chamber 9 and is released. Its working process is shown in Fig. 12 and Fig. 13, wherein Fig. 12 is a schematic diagram of the working process of one of the drug-releasing drivers being releasing the drug, and Fig. 13 is a schematic diagram of one of the drug-releasing drivers having completed the drug-releasing process. The medicine 16 to be released in the schematic diagram is a liquid preparation, and may also be a powder preparation, or a microparticle preparation, or a tablet preparation during implementation.

The length of the digitized pulse-release electronic capsule of this embodiment is between 20-40 mm, and the diameter is between 6-15 mm. The preferred size is 29 mm in length and 11 mm in diameter. The capsule shell 1 is made of medical plastic, such as polycarbonate material. The digitized pulse generating circuit in this embodiment includes a micro-single-chip microcomputer or a micro-ASIC, and the size of the single-chip microcomputer meets the size and energy consumption requirements of the capsule. The start switch is a magnetically controlled switch that is normally closed. Before the capsule is swallowed, the magnetically controlled switch is close to a permanent magnet. The circuit of the medicine electronic capsule is disconnected, and after swallowing, the magnetic control switch is closed, the circuit is turned on, and the digitized pulse generating circuit 4 starts to work.

Fig. 15 is a pulse signal generation process of a drug release and the corresponding plasma concentration curve of the digital pulse drug release electronic capsule including 6 micro drug storage chambers in this embodiment. The digital pulse drug release electronic capsule sends out drug release pulse signals at 6 hours, 12 hours, 14 hours, 16 hours, 18 hours, and 24 hours after swallowing, and the drugs are released from different miniature drug storage bins at the above time points After coming out, the drug enters the blood circulation system through the digestive tract to generate a corresponding blood drug concentration curve, and 6 blood drugs are produced in the intervals around 6 hours, 12 hours, 14 hours, 16 hours, 18 hours, and 24 hours after swallowing. Concentration peaks to achieve a specific therapeutic effect, and 4 drug releases between 12 and 18 hours after ingestion with a time interval of only 2 hours, thus forming near the interval of 12 and 18 hours after ingestion A relatively large blood concentration area is established to achieve a specific therapeutic effect. This example shows that a specific blood concentration curve can be obtained by adjusting the interval of the drug release pulse signal, thereby realizing personalized treatment. Advantages that formulations do not have.

Claims (7)

1. Digital pulse drug release electronic capsule, including shell, power supply, start switch, it is characterized in that said digital pulse drug release electronic capsule includes digital pulse generation circuit and array type drug release device, said array type drug release device includes a drug release device A drug driver array and a drug storage bin array, the drug release driver array includes N drug release micro-drivers, the drug storage bin array includes N micro drug storage bins, where N is a natural number greater than or equal to 2 and less than 1000, each release The drug microdriver and a micro drug storage chamber constitute a micro drug release unit. The micro drug storage chamber is used to package the drug to be released. Each drug release micro drive has a circuit connection with the digital pulse generation circuit, and the digital pulse generation circuit is set according to the preset The pulse electrical signal of specific intensity is generated at the frequency and interval, and the pulse electrical signal is respectively applied to each drug release micro-driver in the array drug releaser according to the predetermined time sequence, and triggers the work of the drug release micro-driver to release the drug out of the micro-driver. Medicine storage warehouse. 2. The electronic capsule for digital pulse release according to claim 1, characterized in that: the drug release micro-driver in the array type drug release device is a micro-chemical thruster, and the micro-chemical thruster includes an igniter, Propellant chamber, propellant. 3. The electronic capsule for digital pulse release drug according to claim 2, characterized in that: the micro medicine storage chamber includes a piston, and the piston is packaged between the propellant chamber and the micro medicine storage chamber. 4. The electronic capsule for digital pulse release according to claim 1, characterized in that: the drug release micro-driver in the array type drug release device is a micro-mechanical propeller, and the micro-mechanical propeller includes a micro-heating resistor , the microspring, the spring fixing bracket, the spring fixing bracket and the micro heating resistor are fixedly connected through a low-melting point adhesive or through a low-melting point polymer wire, and the microspring is in a compressed state. 5. The electronic capsule with digital pulse release according to claim 4, characterized in that: the micro drug storage bin includes a piston, and the piston is packaged between the spring fixing bracket and the micro drug storage bin. 6. The electronic capsule for digital pulse release according to claim 1, characterized in that: the digital pulse generating circuit includes a micro-single-chip microcomputer or a micro-ASIC. 7. The digital pulse drug release electronic capsule according to claim 1, characterized in that: the start switch is a magnetically controlled switch that is in a closed state under normal conditions.

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