Portable insulin administration equipment

Abstract

The invention relates to the technical field of biomedical engineering, and particularly discloses a portable insulin administration device which comprises a noninvasive blood glucose detection module, an insulin administration module, an insulin administration module and an insulin administration module which are sequentially arranged from bottom to top, and the noninvasive blood glucose detection module is used for monitoring the blood glucose concentration of a human body based on a counter-ion electroosmosis technology; the drug loading module is used for loading drugs, and the drugs comprise insulin; the transdermal drug delivery module is connected with the drug carrying module and used for applying pulse voltage to the skin to enhance the transdermal permeation efficiency of the skin when the monitored blood glucose concentration value is larger than a preset threshold value and driving the drug in the drug carrying module to permeate into the corium layer. The equipment monitors the blood sugar concentration of a human body in real time by adopting a counter-ion electroosmosis technology, realizes transdermal delivery of insulin through an electroporation technology, combines two functions of blood sugar concentration monitoring and insulin delivery, realizes integrated closed-loop control of symptom diagnosis and treatment, and can realize the two functions in a completely non-invasive manner, so that the operation is simple and convenient. The skin of a patient is not damaged.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical engineering, and in particular relates to a portable insulin delivery device. Background Art

[0002] Diabetes is a global chronic disease, and patients need long-term blood sugar monitoring and insulin treatment to maintain stable blood sugar levels. Traditional diabetes management methods usually include frequent fingertip blood sampling to detect blood sugar levels and subcutaneous insulin injection to control blood sugar. Although these methods are effective, they have obvious shortcomings: first, frequent blood sampling causes pain and inconvenience to patients; second, subcutaneous insulin injection may cause local tissue damage and infection risks; in addition, although traditional insulin pump devices can provide continuous insulin infusion, their invasiveness and inconvenience limit the daily quality of life of patients. In addition, the existing technology treats blood glucose monitors and insulin delivery micropumps as two independent devices, which brings great inconvenience to users. Based on this, the existing technology proposes a method that integrates blood glucose monitoring and insulin delivery, realizes blood glucose monitoring at the same time, and controls the delivery module to deliver the drug based on the blood glucose monitoring results.

[0003] For example, CN119158115A provides a good use effect of the application device for treating diabetes, which is provided with an electric telescopic rod, a movable plate, a detection needle and a blood glucose meter. Before insulin injection, the electric telescopic rod pulls the movable plate, so that the detection needle is inserted into the patient's skin, and then the patient's blood is tested; the electric telescopic rod moves the movable plate to a central position relative to the fixed plate, avoiding the discomfort caused by the needle being inserted into the skin for a long time, and has the advantages of good use effect and diverse functions; and by providing a treatment needle, a micro pump and a placement shell, the insulin bottle is placed in the inner cavity of the placement shell, the micro pump is used to extract insulin, and the electric telescopic rod pushes the movable plate. At this time, the vertical rod moves in the triangular groove, so that the treatment needle is inserted into the patient's skin, and insulin enters the treatment needle through the catheter. The treatment needle injects an appropriate amount of insulin into the patient's body, achieving the treatment operation of diabetes with good use effect. However, this device causes trauma to the skin during the blood glucose monitoring and insulin injection processes, lacks intelligence, and increases the pain and inconvenience of the patient.

[0004] For example, Yiqun Liu et al. wrote in Microsystems & nanoengineering, 2024, 10(1):112: “A wearable, rapidly manufacturable, stability-enhancing microneedle patch for closed-loop diabetes management”, in which they proposed a wearable, rapidly manufacturable, stability-enhancing microneedle patch for diabetes management. The patch consists of a graphene composite ink printed sensor on a hollow microneedle, an electroosmotic micropump with integrated microneedles, and a circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channel, with the characteristics of long duration. However, the microneedle patch needs to penetrate the skin and is susceptible to passivation and contamination caused by the tissue environment, which can easily cause inflammation and infection during long-term use.

[0005] However, these insulin delivery devices all involve invasive testing and / or invasive delivery methods. These methods involve piercing the skin with a needle to collect blood samples for blood glucose testing, and / or using microneedles to pierce the skin to detect glucose in the interstitial fluid. These devices can cause pain, discomfort, and potential infection risks for patients, and fail to fully meet patients' needs for safer, more convenient, and intelligent treatment options. In recent years, with the rapid development of wearable technology, non-invasive blood glucose monitoring and transdermal drug delivery have become research hotspots in the field of diabetes management.

[0006] Among non-invasive blood glucose monitoring technologies, electroosmosis technology is a non-invasive blood glucose monitoring method. By using electric fields to drive the movement of ions in body fluids, it can achieve real-time and continuous blood glucose monitoring, avoiding the inconvenience and pain of traditional blood sampling methods.

[0007] For example, patent application CN105486731A discloses a non-invasive blood glucose detection probe based on terahertz enhancement. This probe combines two detection modules and a DSP microprocessor via a polymer housing. Each detection module includes an electrochemical sensor and a terahertz counter-ion permeation enhancement array. This terahertz array enhances glucose concentration in the tissue fluid being detected, significantly improving the electrochemical sensor's accuracy in measuring glucose levels and enabling highly sensitive, accurate, rapid, and non-invasive blood glucose measurement in humans.

[0008] Among transdermal drug delivery technologies, electroporation shows great potential. Electroporation applies short, high-voltage pulses to the skin surface, temporarily increasing the permeability of cell membranes and thereby promoting the transdermal absorption of drugs (such as insulin). This method not only avoids the pain and infection risks of traditional injections but also improves drug delivery efficiency.

[0009] For example, patent application CN108355241A discloses a transdermal drug delivery device and apparatus that obtains characteristic parameters corresponding to a drug to be transdermally delivered; searches for electrical stimulation parameters corresponding to the characteristic parameters based on a pre-defined relationship between the characteristic parameters and electrical stimulation parameters; and generates an electrical pulse signal based on the searched electrical stimulation parameters to be applied to the site of drug delivery. Because the corresponding electrical stimulation parameters can be automatically selected based on different characteristic parameters, this increases the diversity of electrical stimulation parameters, enabling more efficient transdermal drug delivery.

[0010] For example, the invention patent application with publication number CN101926784A discloses a conductive hydrogel patch for transdermal drug delivery using a transient pulse electric field. The paste of the conductive hydrogel patch of traditional Chinese medicine obtained by stirring is applied to a medical non-woven fabric, and then combined with a transient pulse electric field to promote the transdermal absorption of multiple components of traditional Chinese medicine, thereby solving the problem of inconvenience in medication for patients who cannot take medication continuously due to gastrointestinal adverse reactions and liver and kidney damage caused by long-term oral medication.

[0011] However, existing technologies still use the non-invasive blood glucose monitoring unit and the non-invasive insulin delivery micropump as two separate devices. These devices lack intelligent judgment of blood glucose levels and the timing of insulin administration, requiring manual administration and lacking closed-loop control. This not only inconveniences users, but also increases treatment costs if users purchase both devices. Therefore, there is an urgent need for a portable device that integrates both non-invasive blood glucose monitoring and non-invasive insulin delivery. Summary of the Invention

[0012] The purpose of the present invention is to provide a portable insulin delivery device to partially solve or alleviate the above-mentioned deficiencies in the prior art. The device can perform blood glucose monitoring through a non-invasive blood glucose monitoring module and trigger the non-invasive insulin delivery device to deliver insulin according to the blood glucose monitoring results. The device is small in size and simple in structure, making it easy to carry, so that users can solve the problems of blood glucose monitoring and automatic delivery with one device.

[0013] In order to solve the above-mentioned technical problems, the present invention specifically adopts the following technical solutions: The present invention provides a portable insulin delivery device, which comprises the following components arranged in order from bottom to top: Non-invasive blood glucose detection module, used to monitor human blood glucose concentration based on reverse ion electroosmosis technology; a drug loading module, used for loading drugs, wherein the drugs include insulin; a transdermal drug delivery module connected to the drug loading module, for applying a pulse voltage to the skin to enhance the transdermal permeation efficiency of the skin and driving the drug in the drug loading module to penetrate into the dermis when the monitored blood glucose concentration value is greater than a preset threshold; Wherein, the transdermal drug delivery module comprises: The first judgment unit is configured to obtain the blood glucose concentration value G monitored in real time by the non-invasive blood glucose detection module, and judge whether the monitored current blood glucose concentration value G is greater than a preset warning threshold; a first calculation unit configured to match a corresponding current medication parameter in a pre-stored table of correspondences between blood glucose concentrations and medication parameters based on the current blood glucose concentration when the judgment unit determines that the current blood glucose concentration is greater than a preset warning threshold; a second calculation unit configured to match the current medication parameter to a corresponding current pulse parameter in a pre-stored medication parameter and pulse parameter correspondence table based on the current medication parameter; an electroporation electrode configured to apply a pulsed voltage to the skin; The pulse generating unit is configured to generate corresponding electric pulses based on the pulse parameters and apply the electric pulses through the electroporation electrodes.

[0014] In some embodiments, the transdermal drug delivery module further comprises: The second judgment unit is configured to judge the current blood glucose concentration value G c Is it greater than or equal to the preset early warning threshold G th , The third judgment unit is configured to, when the second judgment unit judges the current blood glucose concentration value G c Greater than or equal to the preset early warning threshold G th When the value of the threshold is calculated, the difference between the threshold value and the preset early warning threshold value G th and determines whether the difference is greater than or equal to the preset difference threshold ΔG. th ; The fourth judgment unit is configured to: when the third judgment unit judges that ΔG≥ΔG th , and the difference △G is greater than or equal to the preset difference threshold △G th When the duration T of the state is greater than or equal to the preset time threshold T0, the rising rate and acceleration of the blood glucose concentration are calculated based on the multiple blood glucose concentration values ​​monitored during the duration T; The pulse parameter configuration unit is configured to match the corresponding pulse parameter in the blood glucose concentration-pulse parameter comparison table pre-stored in the database based on the current blood glucose concentration value when judging whether the rising rate is greater than or equal to the preset rate threshold and whether the acceleration is greater than or equal to the first preset acceleration threshold, and when judging that the rising rate is greater than or equal to the preset rate threshold and the acceleration is greater than or equal to the first preset acceleration threshold.

[0015] In some embodiments, the non-invasive blood glucose detection module includes: An extraction electrode for non-invasively extracting glucose from interstitial fluid based on reverse ion electroosmosis technology; a working electrode, configured to convert the glucose concentration extracted by the extraction electrode into a corresponding electrical signal; A data processing unit is electrically connected to the extraction electrode and the working electrode, and is used to apply a constant current to the extraction electrode and a constant voltage to the working electrode; and calculate the current glucose concentration based on the electrical signal converted by the working electrode.

[0016] In some embodiments, the drug-carrying module is a hydrogel and is connected to the extraction electrode and the working electrode.

[0017] In some embodiments, the transdermal drug delivery module further includes: a fifth judgment unit, configured to obtain the most recent N historical records of applied pulse voltages, which include the observed blood glucose concentration value after the first specified observation period T2 after each application of the pulse voltage, and calculate the absolute value of the deviation between each observed blood glucose concentration value and the corresponding expected blood glucose concentration value, and then calculate the average of the N deviation values, and determine whether the average is greater than or equal to a preset deviation threshold; if the average is greater than the preset deviation threshold, trigger the above-mentioned pulse parameter configuration unit to adjust the pulse parameters according to the average, wherein the relationship between the pulse parameter change Y and the average X is: , 0.5< k ≤1.5.

[0018] In some embodiments, the transdermal drug delivery module also includes: a sixth judgment unit, configured to obtain multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within the second specified observation time period T3; and calculate the blood glucose decline rate and decline acceleration based on the obtained multiple blood glucose concentration values, and then identify the hypoglycemia risk level based on the decline rate and decline acceleration. If the current blood glucose decline rate is less than the preset decline rate threshold and the decline acceleration is greater than the preset decline acceleration threshold, it is judged as low risk; if the decline rate is greater than or equal to the preset decline rate threshold, but the decline acceleration is greater than the preset decline acceleration threshold, it is judged as medium risk, and the risk is prompted and recorded; if the decline rate is greater than or equal to the preset decline rate threshold, and the decline acceleration is less than or equal to the preset decline acceleration threshold, it is judged as high risk, and the risk is prompted and recorded.

[0019] In some embodiments, the drug-loaded unit is a drug-loaded hydrogel, and the drug-loaded hydrogel adopts a sodium alginate and calcium chloride cross-linking system, or the drug-loaded hydrogel adopts a chitosan-sodium glycerophosphate thermosensitive system; or the drug-loaded hydrogel adopts a double-layer structure, one layer of which is a pH-responsive polyacrylic acid hydrogel and the other layer is a thermosensitive poloxamer hydrogel; and the electroporation electrode is embedded between the two layers.

[0020] In some embodiments, the portable insulin delivery device further includes: a wireless communication module connected to the first judgment unit, for sending the current blood glucose concentration obtained by the first judgment unit to the user's mobile terminal; and / or, sending the pulse parameters sent by the user's mobile terminal to the pulse generating unit.

[0021] In some embodiments, the electroporation electrodes adopt a gradient interdigital structure; and / or, the electroporation electrodes are arranged in a circular array.

[0022] In some embodiments, the non-invasive blood glucose detection module further includes a reference electrode.

[0023] Beneficial Effects: The present invention provides a noninvasive insulin delivery device that utilizes reverse ion electroosmosis technology to achieve noninvasive, real-time monitoring of human blood glucose concentration and electroporation technology to achieve transdermal insulin delivery, i.e., noninvasive drug delivery. This device combines the functions of blood glucose concentration monitoring and insulin delivery, achieving integrated closed-loop control of symptom diagnosis and treatment. Both functions are completely noninvasive and cause no damage to the patient's skin. Furthermore, a wireless communication module, such as a Bluetooth module, is provided for data transmission, meeting the requirements of intelligence and miniaturization, achieving wearability, improving patient comfort, and alleviating pain, thereby partially resolving or alleviating at least one of the problems mentioned in the aforementioned background technology.

[0024] The blood glucose data processing method provided by the application introduces a difference threshold and a duration as double filtering conditions for analyzing and processing blood glucose data without relying on AI algorithms such as machine learning, greatly reduces the probability of triggering the device to generate pulse voltage due to transient blood glucose fluctuations or device noise, and improves the robustness of the device.

[0025] The blood glucose data processing method provided by the application avoids the problem of poor flexibility caused by setting static fixed pulse parameters by observing the blood glucose concentration after multiple pulse voltage applications, analyzing, and then adjusting the pulse parameters based on the difference between the observation value and the expected blood glucose concentration value, thereby improving the flexibility of the device. Moreover, the risk level is identified based on the blood glucose data after the pulse voltage is applied, greatly improving the safety of the device. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual proportion. Obviously, the drawings described below are some embodiments of the application, and those skilled in the art can obtain other drawings according to these drawings without creative labor.

[0027] Figure 1A FIG. 1 is a schematic structural diagram of an embodiment of the internal structure of a portable insulin administration device according to the application; Figure 1B FIG. 2 is a schematic structural diagram of the whole of an embodiment of the portable insulin administration device according to the application; Figure 2 FIG. 3 is a schematic structural diagram of an embodiment of the portable insulin administration device according to the application; Figure 1B FIG. 4 is a sectional view of an embodiment of the portable insulin administration device according to the application; Figure 3 FIG. 5 is a fluorescence picture of the delivery depth of insulin under electroporation parameters in different embodiments obtained by fluorescence detection, wherein (a) is a fluorescence picture of embodiment 2, and (b) is a fluorescence picture of embodiment 1; Figure 4 FIG. 6 is a use example of the portable insulin administration device according to the application for blood glucose monitoring and administration on the arm or abdomen, respectively; Figure 5 FIG. 7 is a flowchart of an embodiment of the blood glucose data processing method according to the application; Figure 6 FIG. 8 is a flowchart of another embodiment of the blood glucose data processing method according to the application; Figure 7 FIG. 9 is a flowchart of still another embodiment of the blood glucose data processing method according to the application; Figure 8 This is a physical sample picture of the electroporation electrodes arranged in a circular array in the present invention.

[0028] Reference numerals in the figure: top cover 1, circuit control module 2, bottom cover 4, extraction electrode 5, working electrode 6, drug-loaded hydrogel 7, electroporation electrode 8, skin stratum corneum barrier 9, dermis 10. DETAILED DESCRIPTION

[0029] To make the purpose, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0030] Herein, suffixes such as "module," "component," or "unit" used to represent elements are only used to facilitate description of the present invention and have no specific meaning. Therefore, "module," "component," or "unit" may be used interchangeably.

[0031] As used herein, terms such as "upper," "lower," "inner," "outer," "front," "back," "one end," and "the other end" indicate positions or locations based on those shown in the accompanying drawings. These terms are intended solely to facilitate and simplify the description of the present invention and are not intended to indicate or imply that the devices or components referred to must have, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0032] As used herein, unless otherwise expressly specified or limited, the terms "installed," "provided with," and "connected" should be understood broadly. For example, "connected" may refer to a fixed connection, a detachable connection, or an integral connection; it may refer to a mechanical connection, a direct connection, an indirect connection via an intermediate medium, or internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention on a case-by-case basis.

[0033] As used herein, "and / or" includes any and all combinations of one or more of the associated listed items.

[0034] Herein, "plurality" means two or more than two, ie, it includes two, three, four, five, etc.

[0035] As used in this specification, the term "about" typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value.

[0036] In this specification, certain embodiments may be disclosed in a format that is within a range. It should be understood that this description of "within a range" is merely for convenience and brevity and should not be interpreted as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within this range. For example, the description of a range of 1-6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within this range, such as 1, 2, 3, 4, 5, and 6. Regardless of the breadth of the range, the above rules apply.

[0037] See also Figure 1A and Figure 1B The present invention provides a non-invasive treatment device for diabetes, which includes a top cover 1 and a bottom cover 4, and arranged in order from bottom to top in a receiving space formed by the buckling of the top cover 1 and the bottom cover 4: a non-invasive blood glucose detection module, which is used to monitor the blood glucose concentration of the human body based on reverse ion electroosmosis technology; a drug loading module, which is used to load drugs (such as insulin); and a transdermal drug delivery module, which is connected to the drug loading module and is used to apply a pulse voltage to the skin to enhance the transdermal penetration efficiency of the skin when the monitored blood glucose concentration value is greater than a preset threshold value, and at the same time drive the drug in the drug loading module to penetrate into the dermis 10.

[0038] In some embodiments, the non-invasive blood glucose detection module includes: an extraction electrode 5 and a working electrode 6 arranged at the bottom of the drug loading module, wherein the extraction electrode 5 is used to non-invasively extract blood glucose from a user-specified part (e.g., an arm or abdomen, etc.) based on reverse ion electroosmosis technology. Figure 4 The working electrode 6 is used to convert the glucose concentration extracted by the extraction electrode 5 into a corresponding electrical signal; and further includes: a data processing unit electrically connected to the extraction electrode 5 and the working electrode 6, and used to apply a constant current to the extraction electrode 5 and a constant voltage to the working electrode 6; and calculate the user's current glucose concentration based on the electrical signal converted by the working electrode 6.

[0039] Preferably, the working electrode 6 is applied with a constant voltage of -0.05V during operation, and the extraction electrode 5 is operated in a constant current mode with a current value of 50 μA.

[0040] In some embodiments, the transdermal drug delivery module comprises: A judgment unit is used to obtain the blood glucose concentration value G monitored in real time by the non-invasive blood glucose detection module, and to judge whether the current monitored blood glucose concentration value is greater than a preset warning threshold value; a first calculation unit is used to match the corresponding current medication parameter in a pre-stored table of correspondence between blood glucose concentration and medication parameter based on the current blood glucose concentration value when the judgment unit judges that the current blood glucose concentration value is greater than the preset warning threshold value; a second calculation unit is used to match the corresponding current pulse parameter in a pre-stored table of correspondence between medication parameter and pulse parameter based on the current medication parameter; an electroporation electrode 8 is used to apply a pulse voltage to the skin; a pulse generating unit is used to generate a corresponding electric pulse based on the matched current pulse parameter, and to apply the electric pulse through the electroporation electrode 8.

[0041] The above-mentioned table of correspondence between blood glucose concentration and drug administration parameters and the table of correspondence between drug administration parameters and pulse parameters are obtained in advance based on a large number of experiments.

[0042] Since the drug administration is controlled after the blood glucose concentration reaches the warning threshold, and since it takes a certain amount of time for the insulin to take effect, and the administration process also takes a certain amount of time, it is possible that the user's blood glucose concentration will be in a high blood glucose window period for a long time before the insulin takes effect. Therefore, in order to shorten this window period, or even prevent the preset warning threshold from being reached in advance, in other embodiments, the transdermal drug administration module includes the above-mentioned judgment unit, the first calculation unit, the second calculation unit, the electroporation motor, and the pulse generation unit, and the working principles of each module are the same, except that, in this embodiment, the transdermal drug administration module also includes: The second judgment unit is configured to judge the current blood glucose concentration value G c Is it greater than or equal to the preset early warning threshold G th , The third determination unit is configured to, when the second determination unit determines the current blood glucose concentration value G c Greater than or equal to the preset early warning threshold G th When the value of the threshold is calculated, the difference between the threshold value and the preset early warning threshold value G th The difference between them is ΔG=|G c -G th ∣, and determine whether the difference is greater than or equal to the preset difference threshold ΔG th ; The fourth judgment unit is configured to: when the third judgment unit judges that ΔG≥ΔG th , and the difference △G is greater than or equal to the preset difference threshold △G thWhen the duration T of the state is greater than or equal to a preset time threshold T0, the rate of increase and the acceleration of the blood glucose concentration are calculated based on the multiple blood glucose concentration values ​​monitored during the duration T (preferably, the rate of increase is obtained by linearly fitting the multiple blood glucose concentration values ​​within the duration T using the least squares method; and the acceleration is obtained by calculating the multiple blood glucose concentration values ​​within the duration T using the second derivative or difference method); The pulse parameter configuration unit is configured to determine whether the rising rate is greater than or equal to a preset rate threshold, and whether the acceleration is greater than or equal to a first preset acceleration threshold, and when it is determined that the rising rate is greater than or equal to the preset rate threshold, and the acceleration is greater than or equal to the first preset acceleration threshold, the corresponding pulse parameter is matched in a blood glucose concentration-pulse parameter comparison table pre-stored in the database based on the current blood glucose concentration value.

[0043] In this embodiment, drug administration is triggered based on the simultaneous satisfaction of the rising rate and acceleration parameters, significantly reducing the false positive rate associated with using rate as the triggering parameter alone. Existing technologies often use machine learning or neural networks to predict whether blood sugar levels are rising or falling. However, this approach relies heavily on AI and increases equipment costs, making it difficult to implement. Therefore, this embodiment utilizes a dual judgment mechanism based on both rate and acceleration.

[0044] Furthermore, the transdermal drug delivery module further comprises: The fifth judgment unit is configured to obtain the most recent N (for example, 5) historical records of applied pulse voltages, which include the observed blood glucose concentration value after a first specified observation period T2 (for example, 15 minutes) after each application of the pulse voltage, and calculate the absolute value of the deviation between each observed blood glucose concentration value and the corresponding expected blood glucose concentration value (which can be obtained through a large amount of test data), then calculate the average of the N deviation values, and determine whether the average is greater than or equal to a preset deviation threshold; if the average is greater than the preset deviation threshold, trigger the above-mentioned pulse parameter configuration unit to adjust the pulse parameters according to the average, wherein the relationship between the pulse parameter change amount Y and the average value X is: , 0.5< k ≤1.5.

[0045] Preferably, the pulse parameter variation Y refers to the pulse voltage variation.

[0046] Furthermore, the transdermal drug delivery module further comprises: The sixth judgment unit is configured to obtain multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within the second specified observation time period T3; and calculate the blood glucose decline rate and decline acceleration based on the obtained multiple blood glucose concentration values, and then identify the hypoglycemia risk level based on the decline rate and decline acceleration. If the current blood glucose decline rate is less than the preset decline rate threshold and the decline acceleration is greater than the preset decline acceleration threshold, it is judged as low risk; if the decline rate is greater than or equal to the preset decline rate threshold, but the decline acceleration is greater than the preset decline acceleration threshold, it is judged as medium risk, and the risk prompt is recorded; if the decline rate is greater than or equal to the preset decline rate threshold, and the decline acceleration is less than or equal to the preset decline acceleration threshold, it is judged as high risk, and the risk prompt is recorded.

[0047] In some embodiments, the risk prompt may specifically include a voice prompt, and accordingly, the device also includes a voice playback unit.

[0048] Furthermore, the above-mentioned sixth judgment unit is also configured to obtain the most recent M historical records of applied pulse voltage when it is judged to be medium risk or high risk, and judge whether the number of times it is judged to be medium risk or the number of times it is judged to be high risk is greater than or equal to a preset number threshold. If so, the fifth judgment unit is triggered to obtain the most recent N historical records of applied pulse voltage, and adjust the pulse parameters according to the record. The specific adjustment principle can be referred to the description part of the fifth judgment unit, which will not be repeated here.

[0049] In some embodiments, the transdermal drug delivery module includes two operating modes: one is an early intervention mode, and its corresponding operating principles refer to the descriptions of the second to sixth judgment units or the data processing method in the subsequent embodiment 5; the other is a conventional intervention mode, and its corresponding operating principles refer to the descriptions of the first judgment unit, the first calculation unit, and the second calculation unit. Of course, the two operating modes can be selected by the user.

[0050] In some embodiments, the electroporation electrodes 8 adopt a gradient interdigital structure, or the electroporation electrodes are arranged in a circular array, see Figure 8 Its thickness is 60 μm, and its coverage area is slightly smaller than that of the drug-loaded hydrogel 7. During operation, a pulse voltage of 30 V / 5 ms is applied to the skin to enhance transdermal penetration efficiency. Figure 3 (a) is a fluorescence image at 20V / 1ms. The green fluorescence represents the insulin delivery effect. It can be seen that under this voltage parameter, the transdermal delivery depth of insulin is shallow and the amount is small. Figure 3 (b) is a fluorescence image at 30V / 5ms. Under this voltage parameter, the transdermal delivery depth of insulin is deeper and the amount is greater.

[0051] In some embodiments, the drug-loaded module is a drug-loaded hydrogel 7, which is connected to the extraction electrode 5 and the working electrode 6. Preferably, the drug-loaded hydrogel adopts a sodium alginate and calcium chloride crosslinking system, or a chitosan-sodium glycerophosphate temperature-sensitive system; or adopts a double-layer structure, one layer of which is a pH-responsive polyacrylic acid hydrogel and the other layer is a temperature-sensitive poloxamer hydrogel, and the electroporation electrode 8 in the transdermal drug delivery module is embedded between the two layers.

[0052] Preferably, the size of the drug-loaded hydrogel 7 is designed to be 4 cm in length, 3 cm in width, and 0.3 cm in thickness, which can stably load insulin and achieve drug delivery.

[0053] In some embodiments, the data processing unit, judgment unit, first calculation unit, second calculation unit, and pulse generation unit are integrated onto a flexible integrated circuit board (FIC) serving as circuit control module 2. The FIC possesses multi-mode control capabilities, enabling independent regulation of the constant current / constant voltage outputs of the electrochemical electrodes (i.e., extraction electrode 5 and working electrode 6) and the pulse voltage parameters of the electroporation electrode 8.

[0054] In some embodiments, the non-invasive insulin delivery device further includes a wireless communication module connected to the data processing unit, configured to transmit the current blood glucose concentration calculated by the data processing unit to a user's mobile terminal and / or transmit pulse parameters received from the user's mobile terminal to the pulse generating unit. For example, the wireless coil supports Bluetooth data transmission, enabling real-time communication with external devices.

[0055] In some embodiments, the transdermal drug delivery module further includes: a parameter adjustment unit configured to dynamically adjust drug delivery parameters according to historical drug delivery data of the current user stored in a database.

[0056] In other embodiments, the non-invasive insulin delivery device further includes a reference electrode.

[0057] In some embodiments, the overall dimensions of the non-invasive treatment device are optimized to 5 cm long x 4 cm wide x 2.5 cm high. The bottom cover 4 and the top cover 1 are connected by a snap-fit ​​connection to encapsulate the internal module. An opening area is provided in the center of the bottom cover 4, allowing the drug-loaded hydrogel 7 and the extraction electrode 5 and working electrode 6 to directly adhere to the skin surface. The detachable gel module 3 adopts a modular design. When the top cover 1 and the bottom cover 4 are separated, the hydrogel can be easily replaced or the electrodes can be maintained. The electroporation electrode 8 is tightly attached to the top of the drug-loaded hydrogel 7, and the pulsed electric field synergistically enhances the transdermal delivery of insulin.

[0058] Working principle: the extraction electrode 5 first extracts subcutaneous tissue fluid non-invasively through the counter-ion electro-osmosis technology, and the data processing unit and the working electrode 6 analyze the blood glucose concentration in real time; when a high blood glucose signal is detected, the electroporation electrode 8 immediately applies a pulse voltage to instantaneously open the skin keratin layer barrier 9, and drive the insulin in the drug-loaded hydrogel 7 to efficiently penetrate into the dermis 10 under the action of the electric field.

[0059] The non-invasive drug delivery device of the embodiment fuses the counter-ion electro-osmosis monitoring and electroporation drug delivery technologies, and does not need to puncture the skin throughout, significantly reducing the pain of the patient. The device adopts a compact design with a total thickness of only 2.5 cm, and combines with a wireless intelligent control module, and has high-precision monitoring, non-invasive treatment and wearable comfort, effectively solving the problems of invasiveness and complex operation of traditional blood glucose monitoring and insulin pumps.

[0060] Embodiment 1: The embodiment provides a non-invasive insulin drug delivery device (or non-invasive blood glucose monitoring device), which comprises the above-mentioned components, wherein the drug-loaded hydrogel 7 adopts bacterial cellulose hydrogel and chitosan, wherein the chitosan concentration is 1%, and the size is designed to be 4 cm long, 3 cm wide and 0.3 cm thick, which can stably load insulin and realize drug delivery.

[0061] The electroporation electrode 8 is made into a fork structure by a flexible circuit board printing process, has a thickness of 60 μm, and has a coverage area slightly smaller than the drug-loaded hydrogel. When working, a pulse voltage of 30 V / 50 ms is applied to the skin to enhance the transdermal penetration efficiency.

[0062] Embodiment 2: The embodiment provides a non-invasive insulin drug delivery device (or non-invasive blood glucose monitoring device), which comprises the above-mentioned components, wherein the drug-loaded hydrogel adopts a chitosan-glycerol sodium phosphate warm-sensitive system, and the size is adjusted to be 3.5 cm long, 2.5 cm wide and 0.2 cm thick; the electroporation electrode adopts a ring array arrangement, and the applied pulse voltage is adjusted to be 20 V / 100 ms.

[0063] The top cover 1 and the bottom cover 4 are fixed by magnetic attraction, and specifically, the bottom cover 4 is provided with a magnetic ring corresponding to the top cover 1.

[0064] The constant current of the extraction electrode 5 is 40 μA, and the constant voltage of the working electrode 6 is -0.3 V.

[0065] During preparation of the hydrogel, 2% chitosan solution and 10% glycerol phosphate sodium are mixed in a volume ratio of 3:1 to form a thermoreversible gel at 37°C, and the insulin loading capacity reaches 25 IU / cm³.

[0066] The flexible circuit board has a thickness of 50 μm, and the interdigital electrode spacing is 200 μm to improve the uniformity of the electric field. Figure 3As shown, the fluorescence pictures of the delivery depth of insulin under the electroporation parameters of Example 1 and Example 2 are obtained by fluorescence detection.

[0067] Example 3: This embodiment provides an insulin non-invasive administration device (or non-invasive blood glucose monitoring device) which maintains the same structure and function as Example 1, but the overall size is reduced to 3.8 cm long x 3 cm wide x 2 cm high, so it can be worn on different parts of the body, such as Figure 5 As shown, the drug-loaded hydrogel adopts a hyaluronic acid-nanocellulose composite material, the thickness is reduced to 0.15 cm, and the oxygen permeability is increased by 40%. The electroporation electrode adopts a tapered interdigital width design (50 μm in the center gradually increasing to 200 μm at the edge), and a 10V / 200ms low-frequency pulse is applied. The circuit control module integrates an AI algorithm, which can dynamically adjust the administration parameters according to historical data. The electrochemical detection adopts differential pulse voltammetry, the working electrode scanning range is-0.1V to +0.5V, and the electrode is extracted synchronously with the application of 50Hz alternating current. The packaging adopts overall coating with medical-grade silicone, and the waterproof level reaches IP68.

[0068] Example 4: This embodiment provides an insulin non-invasive administration device (or non-invasive blood glucose monitoring device) which maintains the same structure and function as Example 1, but this embodiment adopts a double hydrogel layer structure, the upper layer is a pH-responsive polyacrylic acid hydrogel (thickness 0.1 cm), and the lower layer is a temperature-sensitive poloxamer hydrogel (thickness 0.2 cm). The electroporation electrode is embedded between the two layers, and a amplitude modulation pulse (30V / 50ms fundamental wave superimposed with 10kHz carrier wave) is applied. The circuit control module is provided with an impedance monitoring unit to real-time feedback skin state adjustment parameters. The electrochemical detection adopts a three-electrode system, and a new reference electrode is added to improve the measurement accuracy. The extraction current is subjected to fuzzy PID control (set value 60 μA±5%), and the working electrode adopts constant potential-0.4V combined with alternating impedance spectrum analysis.

[0069] Example 5: Based on the above non-invasive blood glucose monitoring device, the present application further provides a blood glucose data processing method, specifically, referring to Figure 5 , the data processing method comprises: S101 acquiring the blood glucose concentration value monitored by the non-invasive blood glucose detection module in real time.

[0070] As described in the above embodiments, the non-invasive blood glucose detection module can monitor the blood glucose concentration value of the monitored user in real time, therefore, the host device of the device (including the first to sixth judgment units in the above embodiments) can directly acquire the blood glucose concentration value of the monitored user from the non-invasive blood glucose detection module.

[0071] S102 judging whether the current blood glucose concentration value is greater than or equal to the preset early warning threshold value, if yes, executing step S103, otherwise, executing step S101.

[0072] In order to avoid the problem that the high blood glucose window period is long when the device is controlled to generate the corresponding pulse voltage only when the early warning threshold value indicating that the drug needs to be administered is monitored, in the embodiment, an early warning threshold value is set as a trigger mechanism.

[0073] In some embodiments, the current working mode can be set in advance in the device, one being a fasting mode and the other being a postprandial mode; accordingly, different early warning threshold values (specifically, the early warning threshold value is less than the aforementioned early warning threshold value) are set in advance for the fasting mode and the postprandial mode.

[0074] In some embodiments, the preset early warning threshold value ranges from [early warning threshold value-2.24 mmol / L, early warning threshold value-0.84 mmol / L], so as to ensure that there is enough time for trend analysis and also prevent the subsequent mechanism from being triggered too early.

[0075] For example, the fasting blood glucose concentration of a long-term type 2 diabetes patient is usually monitored to reach 7 mmol / L (early warning threshold value I), or the postprandial blood glucose concentration reaches 10 mmol / L (early warning threshold value II), and then the device is controlled to generate the corresponding pulse voltage, resulting in a long high blood glucose window period. Therefore, in the embodiment, an early warning threshold value is set, for example, when the fasting blood glucose concentration of the type 2 diabetes patient is monitored to reach 5 mmol / L (early warning threshold value), or the postprandial blood glucose concentration reaches 8 mmol / L (early warning threshold value), the device starts the subsequent “prediction process”, i.e., steps S103-S105.

[0076] For another example, the fasting blood glucose concentration of a newly diagnosed type 2 diabetes patient is usually monitored to reach 11 mmol / L (early warning threshold value I), and then the device is controlled to generate the corresponding pulse voltage, resulting in a long high blood glucose window period. Therefore, in the embodiment, an early warning threshold value is set, for example, when the blood glucose concentration of the patient is monitored to reach 9 mmol / L, the device starts the subsequent “prediction process”, i.e., steps S103-S105.

[0077] When the blood glucose concentration of the user is in an upward trend for a period of time, the device is controlled to generate the corresponding pulse parameter in advance, so that the device generates the corresponding pulse voltage based on the pulse parameter, so as to achieve early intervention and reduce the high blood glucose window period.

[0078] Using algorithms like neural networks to achieve this "prediction" would not only require a large amount of training data but would also significantly increase the cost of the equipment, which would inevitably increase patients' medical costs and hinder product promotion. Therefore, to balance cost and accuracy, this embodiment uses a combination of blood sugar rises over a period of time to perform "prediction." For details, see the following description.

[0079] S103 calculates the difference ΔG between the two and determines whether the difference ΔG is greater than or equal to the preset difference threshold ΔG th If so, and the difference is greater than or equal to the preset difference threshold △G th When the duration T of the state is greater than or equal to the preset time T0, step S104 is executed; otherwise, step S101 is executed.

[0080] S104 calculates the rising rate and acceleration of the blood sugar concentration based on the multiple sugar concentration values ​​monitored during the duration T.

[0081] In some embodiments, the least squares method (which is an existing technology and has a simple calculation method and does not significantly increase the power consumption of the device) can be used to perform linear fitting on multiple blood glucose concentration values ​​within the duration T (for example, 10 minutes to 15 minutes). This algorithm is an existing technology and will not be described in detail here. Its calculation method is simple and does not significantly increase the power consumption of the device.

[0082] In some embodiments, the blood glucose acceleration within the duration T (e.g., 10 min-15 min) can be calculated using a quadratic derivative or differential method. This algorithm is a prior art and will not be described in detail here. The calculation method is simple and will not significantly increase the power consumption of the device.

[0083] S105 determines whether the rising rate is greater than or equal to a preset rate threshold, and the acceleration is greater than or equal to a first preset acceleration threshold; if so, execute step S106, otherwise, execute step S101.

[0084] S106 matches the corresponding pulse parameters in the blood glucose concentration-pulse parameter comparison table pre-stored in the database based on the current blood glucose concentration.

[0085] In some embodiments, a large number of clinical trials are conducted in advance to obtain the required insulin dosages for different blood glucose concentrations and the pulse parameters for different insulin dosages, thereby obtaining a pulse parameter relationship correspondence table corresponding to different blood glucose concentration values.

[0086] In some embodiments, since it is the early warning threshold set, and the blood glucose value of the user is dynamically changing, if only the greater than or equal to the early warning threshold is determined to control the device to generate the pulse voltage, the calculation amount of the device will inevitably be increased, thereby increasing the power consumption, and the misjudgment is easy to occur. Therefore, in the embodiment, when it is monitored that the current blood glucose concentration value is greater than the preset early warning threshold, the difference between the two is calculated, and when the difference is greater than or equal to the preset difference threshold, that is, after exceeding the preset early warning threshold by a certain degree, and the state lasts for a period of time T (for example, 5-15 minutes), and the blood glucose concentration shows an upward trend in the time period, for example, the rising rate is greater than or equal to the preset rate threshold (for example, set to 1.5mg / dL / min-2mg / dL / min according to clinical experience), and the acceleration is greater than or equal to the first preset acceleration threshold (for example, 0.1mg / dL / min 2 -0.3mg / dL / min 2 ), the device is controlled to match the current blood glucose concentration value to the corresponding pulse parameter to generate the corresponding pulse voltage.

[0087] In the embodiment, since the early warning threshold is used as the reference, and the blood glucose concentration of the user is dynamically changing, in order to exclude small amplitude fluctuations, the difference threshold AG th is set; the duration threshold is set to determine the stability of the upward trend of the user's blood glucose; the rate threshold is set to identify the risk of rapid rise, and the acceleration threshold is set to predict the steep rising trend that is about to lose control.

[0088] In the embodiment, by judging the rising rate and acceleration, compared with using a fixed threshold, the individual metabolic dynamics characteristics can be more reflected.

[0089] Of course, further, since the fasting and postprandial blood glucose concentrations and their change modes are different, different thresholds are set for fasting and postprandial states respectively, and all the above thresholds are set with different values for fasting and postprandial. The specific values can be obtained by a large number of experiments in advance, and obtained by using statistics, and this part is not the focus of the present application, so it will not be described here.

[0090] Further, on the one hand, in order to verify whether the pulse parameter setting is reasonable, on the other hand, the physiological state of the user at different times or different stages is changing, therefore, it is necessary to judge whether the pulse parameter needs to be adjusted according to the hypoglycemic effect after each administration. Specifically, referring to Figure 6 , the embodiment further comprises the steps of: S201 acquiring the latest N times of historical pulse voltage records, and performing step S202.

[0091] In some embodiments, the above-mentioned historical record of applied pulse voltage includes the observed value of blood glucose concentration after a first specified observation period T2 (for example, 15 minutes) after each application of pulse voltage, for example, the actual blood glucose concentration value 15 minutes after the pulse voltage is applied, which is used to subsequently determine whether the pulse parameters are reasonable (as mentioned above, after a large number of clinical trials, different dosages correspond to different pulse parameters. Therefore, determining whether the pulse parameters are reasonable is actually determining whether the amount of insulin is appropriate).

[0092] S202 calculates the absolute value of the deviation between each observed blood glucose concentration value and the corresponding preset expected blood glucose concentration value, and then executes step S203.

[0093] Generally speaking, after applying the pulse voltage, after a period of time, the user's blood glucose concentration will drop to a certain extent under the action of insulin. However, due to different responses to insulin by different users and different physiological states at different times, the actual blood glucose concentration value may not achieve the expected effect after a period of time after administration, for example, it may be less than or greater than the preset expected blood glucose concentration value.

[0094] In some embodiments, each drug has a standard efficacy. For example, insulin has a specific effect on blood sugar levels after a specific time period. This is known in the art and will not be further described here. Accordingly, the expected blood sugar concentration value is the difference between the current blood sugar concentration value before applying the pulse parameter and the corresponding drop value for the drug's efficacy.

[0095] S203 calculates the mean of the N deviation values ​​and determines whether the mean is greater than or equal to a preset deviation threshold; if the mean is greater than the preset deviation threshold, execute step S204; otherwise, execute step S201.

[0096] In some embodiments, if the mean is greater than a preset deviation threshold, it indicates that the observed blood glucose concentration values ​​obtained after multiple consecutive administrations have deviated significantly from the expected blood glucose concentration value, which means that the administration amount may be insufficient or insufficient. Therefore, the pulse parameters need to be adjusted, that is, step S204 is executed. The value of N is an empirical value of 5.

[0097] S204 adjusts the pulse parameter according to the mean value. The relationship between the pulse parameter change Y and the mean value X is: , 0.5< k ≤1.5.

[0098] In some embodiments, since the absolute value is calculated in step S202, if each blood glucose concentration observation value is smaller than the expected blood glucose concentration value (or the blood glucose concentration observation value is smaller than the corresponding expected blood glucose concentration value for a preset number of times, for example, 3 times), it indicates that the drug amount is too large, or the user has high sensitivity to the drug, and thus the pulse parameter is reduced. Similarly, if each blood glucose concentration observation value is larger than the expected blood glucose concentration value (or the blood glucose concentration observation value is larger than the corresponding expected blood glucose concentration value for a preset number of times, for example, 3 times), it indicates that the drug amount is too small, or the user has low sensitivity to the drug, and thus the pulse parameter is increased.

[0099] Further, since the early warning threshold is used as the reference, in order to reduce the risk of hypoglycemia, the blood glucose data monitored by the non-invasive blood glucose detection module within a period of time after each application of the pulse voltage is also needed to be obtained, and whether the user has the risk of hypoglycemia is inferred according to the blood glucose data, to verify whether the pulse parameter is reasonable. Therefore, referring to Figure 7 In other embodiments, the method further comprises the steps of: S301 obtaining a plurality of blood glucose concentration values monitored by the non-invasive blood glucose detection module within a second specified observation period T3, and performing step S302.

[0100] In some embodiments, the second specified observation period T3 is smaller than the first specified observation period T2, for example, 10-15 min.

[0101] S302 calculating the blood glucose decline rate and the decline acceleration based on the obtained plurality of blood glucose concentration values.

[0102] In some embodiments, the blood glucose decline rate can also be obtained by linear fitting of all the blood glucose concentration values within the specified observation period T3 using the least square method, which is a prior art and will not be described here.

[0103] In some embodiments, the blood glucose decline acceleration can also be obtained by the second derivative or difference method, which is a prior art and will not be described here.

[0104] S303 determining the hypoglycemia risk level based on the blood glucose decline rate and the decline acceleration, If the current blood glucose decline rate is smaller than the preset decline rate threshold and the decline acceleration is greater than the preset decline acceleration threshold, at this time the blood glucose is slowly and stably declining, and thus the low risk is determined, and step S101 is performed. If the decline rate is greater than or equal to the preset decline rate threshold, but the decline acceleration is greater than the preset decline acceleration threshold, it indicates that the blood glucose is rapidly declining but not accelerating, and thus the medium risk is determined, and a risk prompt (for example, “there is a risk of hypoglycemia, please eat as soon as possible”) is given, and the risk level is recorded. If the descending rate is greater than or equal to the preset descending rate threshold value and the descending acceleration is less than or equal to the preset descending acceleration threshold value, it is indicated that the blood glucose is rapidly descending and acceleratingly descending, and thus, it is determined as high risk, and a risk prompt (for example, "high risk of hypoglycemia, please eat immediately") is performed, and meanwhile, the risk level thereof is recorded.

[0105] In some embodiments, the preset descending rate threshold value is a clinical experience value of 1.1 mg / dL / min-1.5 mg / dL / min.

[0106] In some embodiments, the preset descending acceleration threshold value is a clinical experience value of (-0.3 mg / dL / min 2 )-0.5 mg / dL / min 2 .

[0107] Further, the blood glucose data processing method of the embodiment further comprises the following steps: S304 acquiring the records of the last M times of historical applied pulse voltage, and determining whether the number of times determined as high risk or the number of times determined as medium risk is greater than or equal to a preset number threshold value, if yes, performing steps S201-S204.

[0108] In the embodiment, the M times are actually an adjustment period, that is, before adjustment, if the blood glucose concentration is the same, the corresponding pulse parameters are the same. Preferably, M≥5, and correspondingly, M≥the preset number threshold value≥3.

[0109] It should be noted that in this document, the terms "comprising", "containing", or any other variant thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or further includes elements inherent to such a process, method, article or apparatus. Without more limitations, the element defined by the statement "comprising a" does not exclude the presence of another identical element in the process, method, article or apparatus including the element.

[0110] The embodiments of the present application are described above in conjunction with the drawings, but the present application is not limited to the specific embodiments described above, and the specific embodiments described above are only illustrative, but not restrictive, and those skilled in the art can make many forms under the inspiration of the present application without departing from the purpose of the present application and the scope protected by the claims, which are all within the protection of the present application.

Claims

1. A portable insulin delivery device, characterized in that: Including the following settings from bottom to top: Non-invasive blood glucose detection module, used to monitor human blood glucose concentration based on reverse ion electroosmosis technology; a drug loading module, used for loading drugs, wherein the drugs include insulin; a transdermal drug delivery module connected to the drug loading module, for applying a pulse voltage to the skin to enhance the transdermal permeation efficiency of the skin and driving the drug in the drug loading module to penetrate into the dermis when the monitored blood glucose concentration value is greater than a preset threshold; Wherein, the transdermal drug delivery module comprises: The first judgment unit is configured to obtain the blood glucose concentration value G monitored in real time by the non-invasive blood glucose detection module, and judge whether the monitored current blood glucose concentration value G is greater than a preset warning threshold; a first calculation unit configured to match a corresponding current medication parameter in a pre-stored table of correspondences between blood glucose concentrations and medication parameters based on the current blood glucose concentration when the judgment unit determines that the current blood glucose concentration is greater than a preset warning threshold; a second calculation unit configured to match the current medication parameter to a corresponding current pulse parameter in a pre-stored medication parameter and pulse parameter correspondence table based on the current medication parameter; an electroporation electrode configured to apply a pulsed voltage to the skin; The pulse generating unit is configured to generate corresponding electric pulses based on the pulse parameters and apply the electric pulses through the electroporation electrodes.

2. A portable insulin delivery device according to claim 1, characterized in that: The transdermal drug delivery module further comprises: The second judgment unit is configured to judge the current blood glucose concentration value G c Is it greater than or equal to the preset early warning threshold G th , The third judgment unit is configured to, when the second judgment unit judges the current blood glucose concentration value G c Greater than or equal to the preset early warning threshold G th When the value of the threshold is calculated, the difference between the threshold value and the preset early warning threshold value G th and determines whether the difference is greater than or equal to the preset difference threshold ΔG. th ; The fourth judgment unit is configured to: when the third judgment unit judges that ΔG≥ΔG th , and the difference △G is greater than or equal to the preset difference threshold △G th When the duration T of the state is greater than or equal to the preset time threshold T0, the rising rate and acceleration of the blood glucose concentration are calculated based on the multiple blood glucose concentration values ​​monitored during the duration T; The pulse parameter configuration unit is configured to match the corresponding pulse parameter in the blood glucose concentration-pulse parameter comparison table pre-stored in the database based on the current blood glucose concentration value when judging whether the rising rate is greater than or equal to the preset rate threshold and whether the acceleration is greater than or equal to the first preset acceleration threshold, and when judging that the rising rate is greater than or equal to the preset rate threshold and the acceleration is greater than or equal to the first preset acceleration threshold.

3. A portable insulin delivery device according to claim 1 or 2, characterized in that: The non-invasive blood glucose detection module includes: An extraction electrode for non-invasively extracting glucose from interstitial fluid based on reverse ion electroosmosis technology; a working electrode, configured to convert the glucose concentration extracted by the extraction electrode into a corresponding electrical signal; A data processing unit is electrically connected to the extraction electrode and the working electrode, and is used to apply a constant current to the extraction electrode and a constant voltage to the working electrode; and calculate the current glucose concentration based on the electrical signal converted by the working electrode.

4. A portable insulin delivery device according to claim 3, characterized in that: The drug-carrying module is a hydrogel and is connected to the extraction electrode and the working electrode.

5. A portable insulin delivery device according to claim 2, characterized in that: The transdermal drug delivery module further comprises: The fifth judgment unit is configured to obtain the most recent N historical records of applied pulse voltages, which include the observed blood glucose concentration value after the first specified observation period T2 after each application of the pulse voltage, and calculate the absolute value of the deviation between each observed blood glucose concentration value and the corresponding expected blood glucose concentration value, and then calculate the average of the N deviation values, and determine whether the average is greater than or equal to a preset deviation threshold; if the average is greater than the preset deviation threshold, trigger the above-mentioned pulse parameter configuration unit to adjust the pulse parameters according to the average, wherein the relationship between the pulse parameter change amount Y and the average value X is: , 0.5< k ≤1.

5.

6. A portable insulin delivery device according to claim 5, characterized in that: The transdermal drug delivery module further comprises: The sixth judgment unit is configured to obtain multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within the second specified observation time period T3; and calculate the blood glucose decline rate and decline acceleration based on the obtained multiple blood glucose concentration values, and then identify the hypoglycemia risk level based on the decline rate and decline acceleration. If the current blood glucose decline rate is less than the preset decline rate threshold and the decline acceleration is greater than the preset decline acceleration threshold, it is judged as low risk; if the decline rate is greater than or equal to the preset decline rate threshold, but the decline acceleration is greater than the preset decline acceleration threshold, it is judged as medium risk, and the risk prompt is recorded; if the decline rate is greater than or equal to the preset decline rate threshold, and the decline acceleration is less than or equal to the preset decline acceleration threshold, it is judged as high risk, and the risk prompt is recorded.

7. The portable insulin delivery device according to claim 1, characterized in that: The drug-loaded unit is a drug-loaded hydrogel, and the drug-loaded hydrogel adopts a sodium alginate and calcium chloride cross-linking system, or the drug-loaded hydrogel adopts a chitosan-sodium glycerophosphate temperature-sensitive system; or the drug-loaded hydrogel adopts a double-layer structure, one layer of which is a pH-responsive polyacrylic acid hydrogel and the other layer is a temperature-sensitive poloxamer hydrogel; and the electroporation electrode is embedded between the two layers.

8. A portable insulin delivery device according to claim 1 or 2, characterized in that: Also includes: a wireless communication module, connected to the first determination unit, and configured to send the current blood glucose concentration obtained by the first determination unit to a user mobile terminal; And / or, sending the pulse parameters sent by the user mobile terminal to the pulse generating unit.

9. The portable insulin delivery device according to claim 4, characterized in that: The electroporation electrodes adopt a gradient interdigital structure; and / or, the electroporation electrodes are arranged in a ring array.

10. The portable insulin delivery device according to claim 2, characterized in that: The non-invasive blood glucose detection module also includes a reference electrode.

Images