A portable insulin delivery device

Abstract

The application relates to the technical field of biomedical engineering, and particularly discloses a portable insulin administration device, which comprises a non-invasive blood glucose detection module arranged from bottom to top and used for monitoring human blood glucose concentration based on a counter-ion electro-osmosis technology; a drug loading module used for loading drugs, wherein the drugs comprise insulin; and a transdermal administration module connected with the drug loading module and used for applying a pulse voltage to skin to enhance the transdermal penetration efficiency of the skin and drive the drugs in the drug loading module to penetrate into a dermis layer when the monitored blood glucose concentration value is greater than a preset threshold value. The device adopts the counter-ion electro-osmosis technology to monitor the human blood glucose concentration in real time, and realizes transdermal delivery of insulin through the electroporation technology, so that the two functions of blood glucose concentration monitoring and insulin delivery are combined, the integration of symptom diagnosis and treatment is realized, and both functions can be realized in a completely non-invasive manner without causing damage to the skin of a patient.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical engineering, and specifically relates to a portable insulin administration device. BACKGROUND

[0002] Diabetes is a global chronic disease, and patients need to monitor blood glucose and administer insulin for a long time to maintain stable blood glucose levels. Traditional diabetes management methods usually include frequent fingertip blood glucose testing and blood glucose control through subcutaneous insulin injection. Although these methods are effective, they have obvious disadvantages: first, frequent blood sampling causes pain and inconvenience to patients; second, subcutaneous insulin injection can cause local tissue damage and infection risk; in addition, although traditional insulin pump devices can provide continuous insulin infusion, their invasiveness and inconvenience limit the quality of life of patients. In addition, the blood glucose monitor and insulin administration micropump in the prior art are two independent devices, which brings great inconvenience to users. Based on this, the prior art proposes to integrate blood glucose monitoring and insulin administration together, to realize blood glucose monitoring and control the administration module to administer based on the blood glucose monitoring result.

[0003] For example, CN119158115A provides a good-use patch device for treating diabetes, which is provided with an electric telescopic rod, a movable plate, a detection needle and a blood glucose detector. Before insulin injection, the movable plate is pulled by the electric telescopic rod to make the detection needle inserted into the patient's skin, and then the patient's blood is detected. The movable plate is moved to the center position opposite to the fixed plate by the electric telescopic rod to avoid the discomfort caused by long-term insertion of the needle into the skin, and has the advantages of good use effect and multiple functions. The device is provided with a treatment needle, a micro pump and a placement shell. The insulin bottle is placed in the inner cavity of the placement shell, the insulin is extracted by the micro pump, and the movable plate is pushed by the electric telescopic rod. At this time, the vertical rod moves in the triangular groove, so that the treatment needle is inserted into the patient's skin, the insulin enters the treatment needle through the catheter, and the appropriate amount of insulin is injected into the patient's body through the treatment needle to realize the treatment operation of diabetes, and the use effect is good. However, the device causes trauma to the skin during blood glucose monitoring and insulin injection, and lacks intelligence, increasing the pain and inconvenience of patients.

[0004] For example, Yiqun Liu et al. in Microsystems & nanoengineering, 2024, 10(1):112, in the article “A wearable, rapidly manufacturable, stability-enhancing microneedle patch for closed-loop diabetes management”, propose a wearable, rapidly manufacturable, stability-enhancing microneedle patch for closed-loop diabetes management, consisting of a sensor printed on a hollow microneedle by graphene composite ink, a micro-pump integrated with the microneedle, 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 long duration. However, the microneedle patch needs to be inserted into the skin and is susceptible to passivation and contamination by the tissue environment, and can easily cause inflammation and infection during long-term use.

[0005] However, the above insulin administration devices are all invasive detection and / or invasive administration methods, i.e. using a detection needle to pierce the skin to collect a blood sample for blood glucose detection, and / or using a microneedle to pierce the skin to detect glucose in the interstitial fluid, which can cause pain, discomfort and potential infection risk to the patient, and cannot fully meet the patient's demand 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 technology have become a research hotspot in the field of diabetes management.

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

[0007] For example, the patent application for invention with publication number CN105486731A discloses a non-invasive blood glucose detection probe based on terahertz enhancement, which combines two detection modules and a DSP microprocessor together through a high polymer shell, wherein each detection module includes an electrochemical sensor and a terahertz counter-ion permeation enhancement array. That is, the terahertz generation array is used to enhance the glucose concentration in the detected tissue fluid, greatly improving the measurement accuracy of the electrochemical sensor for tenting blood glucose, and achieving high sensitivity, accuracy, rapidity and non-invasive human blood glucose measurement.

[0008] In transdermal drug delivery technology, electroporation technology has shown great potential in the field of transdermal drug delivery. Electroporation temporarily increases the permeability of the cell membrane by applying a short high-voltage pulse on the surface of the skin, thereby promoting the transdermal absorption of drugs such as insulin. This method not only avoids the pain and infection risk of traditional injection, but also improves the delivery efficiency of drugs.

[0009] For example, the patent application with publication number CN108355241A discloses a transdermal drug delivery device and apparatus, which obtains characteristic parameters corresponding to the transdermal drug to be delivered; according to the pre-set corresponding relationship between the characteristic parameters and the electric stimulation parameters, the electric stimulation parameters corresponding to the characteristic parameters are searched; and the electric pulse signal is generated according to the searched electric stimulation parameters and acts on the part to be delivered. Since the corresponding electric stimulation parameters can be automatically selected according to different characteristic parameters, the diversity of electric stimulation parameters is improved, and the transdermal drug delivery can be more efficiently completed.

[0010] For another example, the patent application with publication number CN101926784A discloses an electrically conductive hydrogel patch for transdermal drug delivery by instant pulse electric field, which coats the paste of the stirred traditional Chinese medicine electrically conductive hydrogel patch on a medical non-woven fabric, and then combines with the instant pulse electric field to promote the transdermal absorption of multiple components of traditional Chinese medicine, thereby solving the problem of inconvenient medication for patients who cannot continuously take medicine due to gastrointestinal adverse reactions and liver and kidney damage caused by long-term oral medication.

[0011] However, in the prior art, the non-invasive blood glucose monitoring part and the insulin non-invasive drug delivery micropump are still two independent devices, and there is no intelligent judgment of blood glucose level and insulin administration time, so the drug delivery can only be performed manually, and there is a lack of closed-loop control. At the same time, the operation of the user is inconvenient, and if the user wants to purchase two devices at the same time, the treatment cost of the user will be increased. Therefore, there is an urgent need for a portable device integrating non-invasive blood glucose monitoring and insulin non-invasive drug delivery. SUMMARY

[0012] The purpose of the present application is to provide a portable insulin delivery device, which partially solves or alleviates 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 insulin non-invasive drug delivery device to deliver drugs according to the blood glucose monitoring results. The device has a small size and simple structure, is convenient to carry, and enables the user to solve the problems of blood glucose monitoring and automatic drug delivery with one device.

[0013] In order to solve the above-mentioned technical problems, the present application specifically adopts the following technical solutions:

[0014] The present application provides a portable insulin delivery device, which comprises, from bottom to top, a non-invasive blood glucose monitoring module, an insulin non-invasive drug delivery device, and a control module.

[0015] A non-invasive blood glucose detection module used to monitor human blood glucose concentration based on reverse ion electroosmosis technology;

[0016] A drug delivery module for loading drugs, including insulin;

[0017] A transdermal drug delivery module, connected to the drug-carrying module, is used to apply a pulse voltage to the skin when the monitored blood glucose concentration value is greater than a preset threshold, so as to enhance the transdermal permeability of the skin and drive the drug in the drug-carrying module to penetrate into the dermis.

[0018] The transdermal drug delivery module includes:

[0019] The first judgment unit is configured to acquire the blood glucose concentration value G monitored in real time by the non-invasive blood glucose detection module, and to determine whether the monitored current blood glucose concentration value G is greater than the preset warning threshold.

[0020] The first calculation unit is configured to match the corresponding current administration parameter in a pre-stored blood glucose concentration and administration parameter correspondence table based on the current blood glucose concentration value when the judgment unit determines that the current blood glucose concentration value is greater than a preset warning threshold.

[0021] The second calculation unit is configured to match the corresponding current pulse parameter in a pre-stored correspondence table of drug administration parameters and pulse parameters based on the current drug administration parameters;

[0022] Electroporation electrodes are configured to apply pulsed voltages to the skin;

[0023] A pulse generation unit is configured to generate a corresponding electrical pulse based on the pulse parameters and apply the electrical pulse through the electroporation electrode.

[0024] In some embodiments, the transdermal drug delivery module further includes:

[0025] The second judgment unit is configured to judge the monitored current blood glucose concentration value G. c Is it greater than or equal to the preset early warning threshold G? th ,

[0026] The third judgment unit is configured to, when the second judgment unit determines that the current blood glucose concentration value G... c Greater than or equal to the preset early warning threshold G th At that time, calculate its comparison with the preset early warning threshold G. th The difference ΔG between the two values ​​is calculated, and it is determined whether the difference is greater than or equal to a preset difference threshold ΔG. th ;

[0027] The fourth judgment unit is configured to, when the third judgment unit determines that ΔG ≥ ΔG thAnd the difference ΔG is greater than or equal to the preset difference threshold ΔG th When the duration T of the state is greater than or equal to the preset time threshold T0, the rate of increase and acceleration of blood glucose concentration are calculated based on the multiple blood glucose concentration values ​​monitored for the duration T.

[0028] The pulse parameter configuration unit is configured to match the corresponding pulse parameter in a blood glucose concentration-pulse parameter lookup table pre-stored in the database based on the current blood glucose concentration value when it is determined whether the rise 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.

[0029] In some embodiments, the non-invasive blood glucose detection module includes:

[0030] Extraction electrode, used for non-invasive extraction of glucose from interstitial fluid based on reverse ion electroosmosis technology;

[0031] The working electrode is used to convert the glucose concentration extracted by the extraction electrode into a corresponding electrical signal.

[0032] A data processing unit, electrically connected to the extraction electrode and the working electrode, is used to apply a constant current to the extraction electrode and a constant voltage to the working electrode; and to calculate the current glucose concentration based on the electrical signal converted by the working electrode.

[0033] In some embodiments, the drug delivery module is a hydrogel and is connected to the extraction electrode and the working electrode.

[0034] In some embodiments, the transdermal drug delivery module further includes: a fifth judgment unit, configured to acquire the most recent N historical pulse voltage application records, including blood glucose concentration observation values ​​after a first specified observation period T2 following each pulse voltage application, and to calculate the absolute value of the deviation between each blood glucose concentration observation value and the corresponding expected blood glucose concentration value, then calculate the mean of the N deviation values, and determine whether the mean is greater than or equal to a preset deviation threshold; if the mean is greater than the preset deviation threshold, trigger the pulse parameter configuration unit to adjust the pulse parameters according to the mean, wherein the relationship between the pulse parameter change Y and the mean X is: 0.5 < k ≤1.5.

[0035] In some embodiments, the transdermal drug delivery module further includes: a sixth judgment unit, configured to acquire multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within a second specified observation time period T3; and calculate the blood glucose decrease rate and decrease acceleration based on the acquired multiple blood glucose concentration values, and then identify the hypoglycemia risk level based on the decrease rate and decrease acceleration. If the current blood glucose decrease rate is less than a preset decrease rate threshold and the decrease acceleration is greater than a preset decrease acceleration threshold, it is judged as low risk; if the decrease rate is greater than or equal to the preset decrease rate threshold, but the decrease acceleration is greater than the preset decrease acceleration threshold, it is judged as medium risk, and a risk warning is issued and recorded; if the decrease rate is greater than or equal to the preset decrease rate threshold and the decrease acceleration is less than or equal to the preset decrease acceleration threshold, it is judged as high risk, and a risk warning is issued and recorded.

[0036] In some embodiments, the drug-loading unit is a drug-loaded hydrogel, and the drug-loaded hydrogel adopts a sodium alginate and calcium chloride crosslinking system; or, the drug-loaded hydrogel adopts a chitosan-sodium glycerophosphate thermosensitive system; or, the drug-loaded hydrogel adopts a bilayer structure, wherein one layer 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.

[0037] In some embodiments, the portable insulin delivery device further includes: a wireless communication module connected to the first judgment unit, used to send the current blood glucose concentration obtained by the first judgment unit to a user mobile terminal; and / or to send pulse parameters sent by the user mobile terminal to the pulse generation unit.

[0038] In some embodiments, the electroporation electrodes adopt a gradient interdigitated structure; and / or, the electroporation electrodes are arranged in a ring array.

[0039] In some embodiments, the non-invasive blood glucose detection module further includes a reference electrode.

[0040] Beneficial Effects: This invention provides a non-invasive insulin delivery device. The device employs reverse iontophoresis technology to achieve non-invasive real-time monitoring of blood glucose concentration and uses electroporation technology to deliver insulin transdermally, thus combining blood glucose monitoring and insulin delivery functions. This achieves integrated closed-loop control of symptom diagnosis and treatment, and both functions are completely non-invasive, causing no damage to the patient's skin. Furthermore, a Bluetooth module or other wireless communication module is included for data transmission, meeting the requirements of intelligence and miniaturization, enabling wearable functionality, improving patient comfort, reducing pain, and partially solving or alleviating at least one of the problems mentioned in the background art.

[0041] The blood glucose data processing method provided by this invention introduces difference threshold and duration as dual filtering conditions to analyze and process blood glucose data without relying on AI algorithms such as machine learning. This greatly reduces the probability of the device generating pulse voltage due to short-term blood glucose fluctuations or device noise, and improves the robustness of the device.

[0042] The blood glucose data processing method provided by this invention analyzes and adjusts pulse parameters based on the observed blood glucose concentration values ​​after multiple pulse voltage applications, and then adjusts the pulse parameters based on the difference between these observed values ​​and the expected blood glucose concentration values. This avoids the problem of poor flexibility caused by setting static, fixed pulse parameters, thus improving the flexibility of the device. Furthermore, it identifies risk levels based on the blood glucose data after applying pulse voltage, greatly improving the safety of the device. Attached Figure Description

[0043] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0044] Figure 1A This is a schematic diagram of the internal structure of an embodiment of a portable insulin delivery device according to the present invention;

[0045] Figure 1B This is a schematic diagram of the overall structure of an embodiment of a portable insulin delivery device according to the present invention.

[0046] Figure 2 for Figure 1B A cross-sectional view of an embodiment of the portable insulin delivery device shown.

[0047] Figure 3 The images show fluorescence images of insulin delivery depth under different electroporation parameters obtained by fluorescence detection, where (a) is the fluorescence image of Example 2 and (b) is the fluorescence image of Example 1.

[0048] Figure 4 Examples of the use of the portable insulin delivery device of the present invention for blood glucose monitoring and drug delivery in the arm or abdomen, respectively;

[0049] Figure 5 A flowchart of an embodiment of the blood glucose data processing method of the invention;

[0050] Figure 6This is a flowchart of another embodiment of the blood glucose data processing method of the present invention;

[0051] Figure 7 This is a flowchart of another embodiment of the blood glucose data processing method of the present invention;

[0052] Figure 8 This is a physical sample of the electroporation electrodes arranged in a ring array according to the present invention.

[0053] The attached diagram is labeled as follows: 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 Implementation

[0054] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0055] In this document, suffixes such as "module," "part," or "unit" used to denote elements are used only for the purpose of illustrative purposes and have no specific meaning in themselves. Therefore, "module," "part," or "unit" may be used interchangeably.

[0056] In this document, the terms "upper," "lower," "inner," "outer," "front," "rear," "one end," and "the other end," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the present invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated 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.

[0057] In this document, unless otherwise explicitly specified and limited, the terms "installed," "equipped with," "connected," etc., should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium; it can be a connection within two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0058] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0059] In this article, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0060] As used in this specification, the term "about" typically means + / -5% of the value, more typically + / -4%, more typically + / -3%, more typically + / -2%, even more typically + / -1%, even more typically + / -0.5%.

[0061] In this specification, certain embodiments may be disclosed in a range-bound format. It should be understood that this "range-bound" description is merely for convenience and brevity and should not be construed as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered as having specifically disclosed all possible subranges and the individual numerical values ​​within those ranges. For example, a description of the range 1-6 should be considered as having 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., and the individual numbers within those ranges, such as 1, 2, 3, 4, 5, and 6. This rule applies regardless of the breadth of the range.

[0062] See Figure 1A and Figure 1B This invention provides a non-invasive treatment device for diabetes, comprising a top cover 1 and a bottom cover 4, and, from bottom to top, a receiving space formed by the snapping of the top cover 1 and the bottom cover 4: a non-invasive blood glucose detection module for monitoring human blood glucose concentration based on reverse ion electroosmosis technology; a drug loading module for loading drugs (e.g., insulin); and a transdermal drug delivery module connected to the drug loading module, for applying 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, and simultaneously driving the drug in the drug loading module to penetrate into the dermis 10.

[0063] In some embodiments, the non-invasive blood glucose detection module includes: an extraction electrode 5 and a working electrode 6 disposed at the bottom of the drug delivery module, wherein the extraction electrode 5 is used for non-invasive extraction from a user-specified site (e.g., arm or abdomen) based on reverse iontophoresis technology. Figure 4 The text describes a process for a glucose concentration in interstitial fluid (as shown in the image). It also includes a working electrode 6 for converting the glucose concentration extracted by the extraction electrode 5 into a corresponding electrical signal, and a data processing unit electrically connected to the extraction electrode 5 and the working electrode 6 for applying a constant current to the extraction electrode 5 and a constant voltage to the working electrode 6, and for calculating the user's current glucose concentration based on the electrical signal converted by the working electrode 6.

[0064] Preferably, a constant voltage of -0.05V is applied to the working electrode 6 during operation, while the extraction electrode 5 operates in constant current mode with a current value of 50μA.

[0065] In some embodiments, the transdermal drug delivery module includes:

[0066] The system includes a judgment unit for acquiring the blood glucose concentration value G monitored in real time by the non-invasive blood glucose detection module and determining whether the monitored current blood glucose concentration value is greater than a preset warning threshold; a first calculation unit for matching the current blood glucose concentration value with the corresponding current drug administration parameter in a pre-stored blood glucose concentration and drug administration parameter correspondence table when the judgment unit determines that the current blood glucose concentration value is greater than the preset warning threshold; a second calculation unit for matching the current drug administration parameter with the corresponding current pulse parameter in a pre-stored drug administration parameter and pulse parameter correspondence table; an electroporation electrode 8 for applying a pulse voltage to the skin; and a pulse generation unit for generating a corresponding electrical pulse based on the matched current pulse parameter and applying the electrical pulse through the electroporation electrode 8.

[0067] The tables showing the correspondence between blood glucose concentration and drug administration parameters, and between drug administration parameters and pulse parameters, were obtained in advance based on a large number of experiments.

[0068] Because drug administration is controlled only after the blood glucose concentration reaches a warning threshold, and because insulin takes time to take effect and the drug administration process also takes time, the user's blood glucose concentration may remain in a hyperglycemic window for a relatively long period before the insulin takes effect. Therefore, in order to shorten this window period and even prevent the aforementioned preset warning threshold from being reached in advance, in some embodiments, the transdermal drug delivery module includes the aforementioned judgment unit, first calculation unit, second calculation unit, electroporation motor, and pulse generation unit, and the working principle of each module is the same. The difference is that in this embodiment, the transdermal drug delivery module also includes:

[0069] The second judgment unit is configured to judge the monitored current blood glucose concentration value G. c Is it greater than or equal to the preset early warning threshold G? th ,

[0070] 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 At that time, calculate its comparison with the preset early warning threshold 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 ;

[0071] The fourth judgment unit is configured to, when the third judgment unit determines that ΔG ≥ ΔG th And the difference ΔG is greater than or equal to the preset difference threshold ΔG th When the duration T of the state is greater than or equal to a preset time threshold T0, the rate of increase and acceleration of blood glucose concentration are calculated based on multiple blood glucose concentration values ​​monitored during the duration T (preferably, the rate of increase is obtained by linearly fitting multiple blood glucose concentration values ​​within the duration T using the least squares method; the acceleration is obtained by calculating multiple blood glucose concentration values ​​within the duration T using the second derivative or the difference method).

[0072] The pulse parameter configuration unit is configured to determine whether the rise 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 rise 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, to match the corresponding pulse parameter in a blood glucose concentration-pulse parameter lookup table pre-stored in the database based on the current blood glucose concentration value.

[0073] In this embodiment, drug administration is triggered based on the simultaneous fulfillment of both the rate of rise and acceleration, significantly reducing the false positive rate when rate is used as the sole triggering parameter. Existing technologies mostly utilize machine learning or neural networks to predict whether blood glucose levels are rising or falling; however, this approach relies too heavily on AI and increases equipment costs, making widespread adoption difficult. Therefore, this embodiment employs a dual-judgment mechanism based on both rate and acceleration.

[0074] Furthermore, the transdermal drug delivery module also includes:

[0075] The fifth judgment unit is configured to acquire the most recent N (e.g., 5) historical pulse voltage application records, including blood glucose concentration observation values ​​after a first specified observation period T2 (e.g., 15 minutes) following each pulse voltage application, and to calculate the absolute value of the deviation between each blood glucose concentration observation value and the corresponding expected blood glucose concentration value (which can be obtained through a large amount of experimental data). Then, the mean of the N deviation values ​​is calculated, and it is determined whether the mean is greater than or equal to a preset deviation threshold. If the mean is greater than the preset deviation threshold, the pulse parameter configuration unit is triggered to adjust the pulse parameters according to the mean, wherein the relationship between the pulse parameter change Y and the mean X is as follows: 0.5 < k ≤1.5.

[0076] Preferably, the change in pulse parameter Y refers to the change in pulse voltage.

[0077] Furthermore, the transdermal drug delivery module also includes:

[0078] The sixth judgment unit is configured to acquire multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within the second specified observation time period T3; calculate the blood glucose decrease rate and decrease acceleration based on the acquired multiple blood glucose concentration values; and then identify the hypoglycemia risk level based on the decrease rate and decrease acceleration. If the current blood glucose decrease rate is less than a preset decrease rate threshold and the decrease acceleration is greater than a preset decrease acceleration threshold, it is judged as low risk; if the decrease rate is greater than or equal to the preset decrease rate threshold, but the decrease acceleration is greater than the preset decrease acceleration threshold, it is judged as medium risk, and a risk warning is issued and recorded; if the decrease rate is greater than or equal to the preset decrease rate threshold and the decrease acceleration is less than or equal to the preset decrease acceleration threshold, it is judged as high risk, and a risk warning is issued and recorded.

[0079] In some embodiments, the risk warning may specifically include a voice prompt, and accordingly, the device also includes a voice playback unit.

[0080] Furthermore, the aforementioned sixth judgment unit is also configured to, when determined to be of medium risk or high risk, acquire the most recent M historical pulse voltage records, and determine whether the number of times it has been determined to be of medium risk or high risk is greater than or equal to a preset number threshold. If so, the fifth judgment unit is triggered to acquire the most recent N historical pulse voltage records, and the pulse parameters are adjusted according to the records. The specific adjustment principle can be found in the description of the fifth judgment unit, which will not be repeated here.

[0081] In some embodiments, the transdermal drug delivery module includes two operating modes: an early intervention mode, the operating principle of which is described in the above description of the second to sixth judgment units or the data processing method in subsequent embodiment 5; and a conventional intervention mode, the operating principle of which is described in the above description of the first judgment unit, the first calculation unit, and the second calculation unit. Of course, the user can choose between the two operating modes.

[0082] In some embodiments, the electroporation electrode 8 adopts a gradient interdigitated structure, or the electroporation electrode is arranged in a ring array, see [reference]. Figure 8 Its thickness is 60μm, and its coverage area is slightly smaller than that of the drug-loaded hydrogel 7. During operation, a pulse voltage of 30V / 5ms is applied to the skin to enhance transdermal penetration efficiency. Figure 3 (a) is a fluorescence image at 20V / 1ms. 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, insulin can be delivered to a deeper depth and in greater quantities through transdermal administration.

[0083] In some embodiments, the drug-loading 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 is a sodium alginate and calcium chloride crosslinking system, or a chitosan-sodium glycerophosphate thermosensitive system; or a bilayer structure, wherein one layer is a pH-responsive polyacrylic acid hydrogel and the other layer is a thermosensitive poloxamer hydrogel, and the electroporation electrode 8 in the transdermal drug delivery module is embedded between the two layers.

[0084] Preferably, the drug-loaded hydrogel 7 is designed to be 4cm long, 3cm wide, and 0.3cm thick, which can stably load insulin and achieve drug delivery.

[0085] In some embodiments, the data processing unit, judgment unit, first calculation unit, second calculation unit, and pulse generation unit described above are integrated on a flexible integrated circuit board as circuit control module 2. The flexible circuit board has multi-mode control function and can independently adjust the constant current / constant voltage output of the electrochemical electrode (i.e., extraction electrode 5 and working electrode 6) and the pulse voltage parameters of the electroporation electrode 8.

[0086] In some embodiments, the non-invasive insulin delivery device further includes: a wireless communication module connected to the data processing unit, used to send the current blood glucose concentration calculated by the data processing unit to a user's mobile terminal; and / or to send pulse parameters sent by the user's mobile terminal to the pulse generating unit. For example, the wireless coil supports Bluetooth data transmission to achieve real-time communication with external devices.

[0087] In some embodiments, the transdermal drug delivery module further includes a parameter adjustment unit, configured to dynamically adjust the drug delivery parameters based on the historical drug delivery data of the current user stored in the database.

[0088] In other embodiments, the non-invasive insulin delivery device also includes a reference electrode.

[0089] In some embodiments, the overall dimensions of the non-invasive treatment device are optimized to be 5cm long × 4cm wide × 2.5cm high. The bottom cover 4 and the top cover 1 are connected by a snap-fit ​​to encapsulate the internal modules. The bottom cover 4 has an opening in the center, allowing the drug-loaded hydrogel 7, extraction electrode 5, and working electrode 6 to directly adhere to the skin surface. The detachable gel module 3 adopts a modular design, allowing for easy replacement of the hydrogel or maintenance of the electrodes when the top cover 1 is separated from the bottom cover 4. The electroporation electrode 8 is tightly attached above the drug-loaded hydrogel 7, enhancing the transdermal delivery of insulin through a pulsed electric field.

[0090] Working principle: The extraction electrode 5 first non-invasively extracts subcutaneous tissue fluid using reverse ion electroosmosis technology. The data processing unit and working electrode 6 analyze blood glucose concentration in real time. When a hyperglycemic signal is detected, the electroporation electrode 8 immediately applies a pulse voltage, instantly opening the skin stratum corneum barrier 9. At the same time, it drives the insulin in the drug-loaded hydrogel 7 to efficiently penetrate into the dermis 10 under the action of the electric field.

[0091] The non-invasive drug delivery device in this embodiment integrates reverse iontophoresis monitoring and electroporation drug delivery technology, eliminating the need for skin punctures and significantly reducing patient discomfort. The device features a compact design with a total thickness of only 2.5cm. Combined with a wireless intelligent control module, it offers high-precision monitoring, non-invasive treatment, and wearable comfort, effectively solving the problems of invasiveness and operational complexity associated with traditional blood glucose monitoring and insulin pumps.

[0092] Example 1: This example provides a non-invasive insulin delivery device (or non-invasive blood glucose monitoring device), which includes the above-mentioned components. The drug-loaded hydrogel 7 is made of bacterial cellulose hydrogel and chitosan, wherein the chitosan concentration is 1%, and its size is designed to be 4cm long, 3cm wide and 0.3cm thick, which can stably load insulin and realize drug delivery.

[0093] Among them, the electroporation electrode 8 is made into an interdigital structure using a flexible circuit board printing process. It has a thickness of 60μm and a coverage area slightly smaller than that of the drug-loaded hydrogel. During operation, it applies a pulse voltage of 30V / 50ms to the skin to enhance transdermal penetration efficiency.

[0094] Example 2: This example provides a non-invasive insulin delivery device (or non-invasive blood glucose monitoring device), which includes the above-mentioned components. The drug-loaded hydrogel adopts a chitosan-sodium glycerophosphate thermosensitive system, and its size is adjusted to 3.5cm in length × 2.5cm in width × 0.2cm in thickness. The electroporation electrodes are arranged in a ring array, and the applied pulse voltage is adjusted to 20V / 100ms.

[0095] The top cover 1 and the bottom cover 4 are fixed together by magnetic attraction. Specifically, the bottom cover 4 is provided with a magnetic ring corresponding to the top cover 1.

[0096] The constant current of the extraction electrode 5 is 40μA, and the constant voltage of the working electrode 6 is -0.3V.

[0097] In the preparation of the hydrogel, 2% chitosan solution and 10% sodium glycerophosphate were mixed at a volume ratio of 3:1 and a thermally reversible gel was formed at 37°C, with an insulin loading capacity of 25 IU / cm³.

[0098] The flexible circuit board has a thickness of 50 μm, and the interdigitated electrode spacing is 200 μm to improve electric field uniformity. For example... Figure 3As shown, fluorescence images of insulin delivery depth obtained by fluorescence detection under the electroporation parameters of Examples 1 and 2 are shown.

[0099] Example 3: This example provides a non-invasive insulin delivery device (or a non-invasive blood glucose monitoring device). Its structure and function are consistent with Example 1, but the overall size is reduced to 3.8cm (length) × 3cm (width) × 2cm (height), thus allowing it to be worn on different parts of the body, such as... Figure 5 As shown. The drug-loaded hydrogel uses a hyaluronic acid-cellulose nanocomposite material, reducing the thickness to 0.15 cm and increasing oxygen permeability by 40%. The electroporation electrode adopts a gradient interdigitated width design (50 μm at the center, gradually increasing to 200 μm at the edge), applying a 10V / 200ms low-frequency pulse. The circuit control module integrates an AI algorithm, which can dynamically adjust the drug delivery parameters based on historical data. Electrochemical detection uses differential pulse voltammetry, with the working electrode scanning range from -0.1V to +0.5V, and a 50Hz alternating current is applied simultaneously to the extraction electrode. The encapsulation uses medical-grade silicone for complete coverage, achieving an IP68 waterproof rating.

[0100] Example 4: This example provides a non-invasive insulin delivery device (or non-invasive blood glucose monitoring device), whose structure and function are consistent with Example 1. However, this example adopts a double hydrogel layer structure, with the upper layer being a pH-responsive polyacrylic acid hydrogel (0.1 cm thick) and the lower layer being a thermosensitive poloxamer hydrogel (0.2 cm thick). An electroporation electrode is embedded between the two layers, and an amplitude-modulated pulse (fundamental wave 30V / 50ms superimposed with a 10kHz carrier wave) is applied. The circuit control module is equipped with an impedance monitoring unit to provide real-time feedback on skin condition adjustment parameters. Electrochemical detection adopts a three-electrode system, with the addition of a reference electrode to improve measurement accuracy. The extraction current is controlled by fuzzy PID (set value 60μA±5%), and the working electrode uses a constant potential of -0.4V combined with AC impedance spectroscopy analysis.

[0101] Example 5: Based on the above-mentioned non-invasive blood glucose monitoring device, the present invention also provides a blood glucose data processing method, specifically, see [link to example]. Figure 5 The data processing method includes:

[0102] S101 acquires the blood glucose concentration value monitored in real time by the non-invasive blood glucose detection module.

[0103] 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 main control device of the device (including the first judgment unit to the sixth judgment unit in the above embodiments) can directly obtain the blood glucose concentration value of the monitored user from the non-invasive blood glucose detection module.

[0104] S102 determines whether the current blood glucose concentration is greater than or equal to the preset early warning threshold. If yes, proceed to step S103; otherwise, proceed to step S101.

[0105] To avoid the problem of a prolonged hyperglycemic window period caused by controlling the device to generate the corresponding pulse voltage only when a warning threshold for drug administration is detected, this embodiment sets an early warning threshold as a triggering mechanism.

[0106] In some embodiments, the current working mode can be preset in the device, one being a fasting mode and the other a post-meal mode; correspondingly, different early warning thresholds are preset for the fasting mode and the post-meal mode (specifically, the early warning threshold is less than the aforementioned warning threshold).

[0107] In some embodiments, the preset early warning threshold ranges from [early warning threshold - 2.24 mmol / L, early warning threshold - 0.84 mmol / L], thereby ensuring sufficient time for trend analysis while preventing excessive premature triggering of subsequent mechanisms.

[0108] For example, typically, the device will only generate a corresponding pulse voltage when the fasting blood glucose concentration of a patient with long-term type 2 diabetes reaches 7 mmol / L (early warning threshold I), or the postprandial blood glucose concentration reaches 10 mmol / L (early warning threshold II), resulting in a prolonged hyperglycemic window. Therefore, in this embodiment, an early warning threshold is set. For example, when the fasting blood glucose concentration of a patient with type 2 diabetes reaches 5 mmol / L (early warning threshold), or the postprandial blood glucose concentration reaches 8 mmol / L (early warning threshold), the device will initiate the subsequent "prediction process," namely steps S103-S105.

[0109] For example, typically, newly diagnosed type 2 diabetes patients will only generate a corresponding pulse voltage when their fasting blood glucose concentration reaches 11 mmol / L (early warning threshold I), resulting in a longer hyperglycemic window. Therefore, in this embodiment, an early warning threshold is set. For example, when the patient's blood glucose concentration reaches 9 mmol / L, the device will initiate the subsequent "prediction process," i.e., steps S103-S105.

[0110] When a user's blood glucose concentration is on an upward trend for a sustained period of time, the device is controlled in advance to generate corresponding pulse parameters. Based on these pulse parameters, the device generates a corresponding pulse voltage to achieve early intervention and reduce the window period for hyperglycemia.

[0111] Using algorithms such as neural networks to achieve this "prediction" would not only require a large amount of training data but also significantly increase the cost of the equipment, which would inevitably increase the medical costs for patients and hinder product promotion and implementation. Therefore, in order to balance cost and ensure a certain level of accuracy, this embodiment combines the rise in blood glucose over a period of time for "prediction," as detailed in the following description.

[0112] 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 If the duration T of the state is greater than or equal to the preset time T0, proceed to step S104; otherwise, proceed to step S101.

[0113] S104 calculates the rate and acceleration of the rise in blood glucose concentration based on multiple glucose concentration values ​​monitored within the duration T.

[0114] In some embodiments, the least squares method (which is existing technology and has a simple calculation method that does not significantly increase device power consumption) can be used to linearly fit multiple blood glucose concentration values ​​within the duration T (e.g., 10 min-15 min). This algorithm is existing technology and will not be described in detail here. Its calculation method is simple and does not significantly increase device power consumption.

[0115] In some embodiments, the blood glucose acceleration during the duration T (e.g., 10 min-15 min) can be calculated using the second derivative or the difference method. This algorithm is existing technology and will not be described in detail here. Its calculation method is simple and will not significantly increase the power consumption of the device.

[0116] S105 determines whether the rate of ascent 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 yes, proceed to step S106; otherwise, proceed to step S101.

[0117] S106 matches the corresponding pulse parameter in the pre-stored blood glucose concentration-pulse parameter lookup table in the database based on the current blood glucose concentration.

[0118] In some embodiments, the insulin dosage required for different blood glucose concentrations and the pulse parameters required for different insulin dosages are obtained in advance through extensive clinical trials, thereby obtaining a pulse parameter relationship table corresponding to different blood glucose concentration values.

[0119] In some embodiments, since an early warning threshold is set and the user's blood glucose level changes dynamically, controlling the device to generate a pulse voltage simply by determining that the value is greater than or equal to the early warning threshold would inevitably increase the device's computational load, thereby increasing power consumption and potentially leading to misjudgments. Therefore, in this embodiment, when the current blood glucose concentration is detected to be greater than the preset early warning threshold, the difference between the two is calculated. Furthermore, when this difference is greater than or equal to a preset difference threshold (i.e., exceeding the preset early warning threshold to a certain extent), and this state persists for a period of time T (e.g., 5-15 minutes), and during this period the blood glucose concentration shows an upward trend—for example, the rate of increase is greater than or equal to a preset rate threshold (e.g., set to 1.5 mg / dL / min-2 mg / dL / min based on clinical experience), and the acceleration is greater than or equal to a first preset acceleration threshold (e.g., 0.1 mg / dL / min)—then... 2 -0.3 mg / dL / min 2 Only when the blood glucose concentration value is reached will the control device match the corresponding pulse parameters to generate the corresponding pulse voltage.

[0120] In this embodiment, since the early warning threshold is used as the basis, and the user's blood glucose concentration changes dynamically, a difference threshold ΔG is set to eliminate interference from small fluctuations. th Setting a duration threshold is to determine the stability of the user's blood glucose rise trend; setting a rate threshold is to identify the risk of rapid rise; and setting an acceleration threshold is to predict an impending out-of-control steep rise.

[0121] In this embodiment, judging the rate of ascent and acceleration is more effective in reflecting individual metabolic dynamics characteristics than using a fixed threshold.

[0122] Of course, furthermore, since fasting and postprandial blood glucose concentrations and their changes are different, different thresholds are set for fasting and postprandial states respectively. All the above thresholds have different values ​​for fasting and postprandial states. The specific values ​​can be obtained in advance through a large number of experiments and statistical analysis. This part is not the focus of this application, so it will not be elaborated here.

[0123] Furthermore, on the one hand, to verify whether the pulse parameters are set reasonably, and on the other hand, because the user's physiological state changes at different times or stages, it is necessary to determine whether the pulse parameters need to be adjusted based on the blood glucose lowering effect after each administration. For details, see [link to relevant documentation]. Figure 6 This embodiment also includes the following steps:

[0124] S201 Obtain the most recent N historical applied pulse voltage records, and proceed to step S202.

[0125] In some embodiments, the above-mentioned historical pulse voltage record includes the blood glucose concentration observation value after a first specified observation period T2 (e.g., 15 min) after each pulse voltage is applied, for example, the actual blood glucose concentration value after 15 min of pulse voltage application, 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).

[0126] S202 Calculate the absolute value of the deviation between each observed blood glucose concentration value and the corresponding preset expected blood glucose concentration value, and then proceed to step S203.

[0127] Generally speaking, after applying a pulse voltage, the user's blood glucose concentration will decrease to a certain extent under the action of insulin after a period of time. However, due to different users' responses to insulin and different physiological states at different times, the actual blood glucose concentration may not reach 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.

[0128] In some embodiments, each drug has its standard efficacy; for example, insulin has a specific duration of administration and a predetermined effect on blood glucose levels, which is prior art and will not be elaborated upon here. Accordingly, the expected blood glucose concentration value is the difference between the current blood glucose concentration value before the application of the pulse parameter and the corresponding decrease value.

[0129] S203 calculates the mean of 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, proceed to step S204; otherwise, proceed to step S201.

[0130] In some embodiments, if the mean value is greater than a preset deviation threshold, it indicates that the observed blood glucose concentration values ​​obtained after multiple consecutive administrations deviate significantly from the expected blood glucose concentration value, which means that the dosage may be insufficient or too low. Therefore, it is necessary to adjust the pulse parameters, i.e., execute step S204. Here, N is taken as an empirical value of 5.

[0131] S204 adjusts the pulse parameters according to the mean value, and the relationship between the pulse parameter change Y and the mean value X is as follows: 0.5 < k ≤1.5.

[0132] In some embodiments, since the absolute value is calculated in step S202 above, if each observed blood glucose concentration is smaller than the expected blood glucose concentration (or for a preset number of times, for example, three observed blood glucose concentrations are all smaller than their corresponding expected blood glucose concentrations), it indicates that the dosage is too high, or the user is highly sensitive to the drug. Therefore, the pulse parameter is decreased. Similarly, if each observed blood glucose concentration is larger than the expected blood glucose concentration (or for a preset number of times, for example, three observed blood glucose concentrations are all larger than their corresponding expected blood glucose concentrations), it indicates that the dosage is too low, or the user is less sensitive to the drug. Therefore, the pulse parameter is increased.

[0133] Furthermore, since the early warning threshold is used as a benchmark, in order to reduce the risk of hypoglycemia, it is also necessary to obtain the real-time blood glucose data monitored by the non-invasive blood glucose detection module for a period of time after each pulse voltage application, and to infer whether the user is at risk of hypoglycemia, thus indirectly verifying the rationality of the aforementioned pulse parameters. Therefore, see Figure 7 In other embodiments, the method further includes the step of:

[0134] S301 Obtain multiple blood glucose concentration values ​​monitored by the non-invasive blood glucose detection module within the second specified observation time period T3, and execute step S302.

[0135] In some embodiments, the second specified observation time period T3 is less than the first specified observation time period T2 described above, for example, 10 min to 15 min.

[0136] S302 calculates the rate and acceleration of blood glucose decrease based on the acquired multiple blood glucose concentration values.

[0137] In some embodiments, the aforementioned rate of decline can also be obtained by linearly fitting all blood glucose concentration values ​​within a specified observation period T3 using the least squares method. This algorithm is existing technology and will not be described in detail here.

[0138] In some embodiments, the aforementioned descent acceleration can also be calculated using the second derivative or the finite difference method. These algorithms are existing technologies and will not be described in detail here.

[0139] S303 determines the risk level of hypoglycemia based on the rate and acceleration of the decline.

[0140] If the current rate of blood glucose decrease is less than the preset rate of decrease threshold and the acceleration of decrease is greater than the preset acceleration of decrease threshold, then the blood glucose decreases slowly and steadily. Therefore, it is determined to be low risk, and step S101 is executed.

[0141] If the rate of decline is greater than or equal to the preset rate of decline threshold, but the rate of decline is greater than the preset rate of decline threshold, it indicates that blood sugar is declining rapidly but not accelerating. Therefore, it is judged as medium risk and a risk warning is issued (e.g., "There is a risk of hypoglycemia, please eat as soon as possible"). At the same time, its risk level is recorded.

[0142] If the rate of decline is greater than or equal to the preset rate of decline threshold, and the acceleration of decline is less than or equal to the preset acceleration of decline threshold, it indicates that blood sugar is declining rapidly and accelerating. Therefore, it is judged as high risk, and a risk warning is issued (e.g., "High risk of hypoglycemia, please eat immediately"). At the same time, its risk level is recorded.

[0143] In some embodiments, the preset rate of decline threshold is a clinically empirical value of 1.1 mg / dL / min to 1.5 mg / dL / min.

[0144] In some embodiments, the preset descent acceleration threshold is a clinically empirical value (-0.3 mg / dL / min). 2 -0.5 mg / dL / min 2 .

[0145] Furthermore, the blood glucose data processing method in this embodiment also includes the following steps:

[0146] S304 acquires the most recent M historical pulse voltage records and determines whether the number of times it was judged as high risk or medium risk is greater than or equal to a preset number threshold. If so, execute steps S201-S204.

[0147] In this embodiment, M times actually represents an adjustment cycle. 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 ≥ preset number threshold ≥ 3.

[0148] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0149] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A portable insulin dosing device, characterized in that, The device comprises, from bottom to top, successively arranged: a non-invasive blood glucose detection module for monitoring blood glucose concentration of a human body based on counter-ion electro-osmosis technology; a drug loading module for loading drugs, the drugs including insulin; a transdermal drug delivery module connected with the drug loading module, for applying a pulse voltage to the skin to enhance the transdermal penetration efficiency of the skin and drive the drugs in the drug loading module to penetrate into the dermis layer when the monitored blood glucose concentration value is greater than a preset threshold value; The transdermal drug delivery module comprises: a first judging unit configured to obtain a blood glucose concentration value G monitored by the non-invasive blood glucose detection module in real time, and judge whether the monitored current blood glucose concentration value G is greater than a preset warning threshold value; a first calculating unit configured to, when the judging unit judges that the current blood glucose concentration value is greater than the preset warning threshold value, match a corresponding current drug delivery parameter in a pre-stored blood glucose concentration and drug delivery parameter corresponding relationship table based on the current blood glucose concentration value; a second calculating unit configured to match a corresponding current pulse parameter in a pre-stored drug delivery parameter and pulse parameter corresponding relationship table based on the current drug delivery parameter; an electroporation electrode configured to apply a pulse voltage to the skin; a pulse generating unit configured to generate a corresponding electric pulse based on the pulse parameter and apply the electric pulse through the electroporation electrode; The transdermal drug delivery module further comprises: a second determination unit configured to determine whether the monitored current blood glucose concentration value G c is greater than or equal to a preset early warning threshold value G th , The third judging unit is configured to calculate the difference AG between the current blood glucose concentration value G and the preset early warning threshold value G when the second judging unit judges that the current blood glucose concentration value G is greater than or equal to the preset early warning threshold value G c ; and judge whether the difference AG is greater than or equal to a preset difference threshold value AG th . th ; and judge whether the difference AG is greater than or equal to a preset difference threshold value AG th . The fourth judging unit is configured to calculate the rising rate and acceleration of the blood glucose concentration based on the plurality of blood glucose concentration values monitored by the duration T when the third judging unit judges that ΔG≥ΔG th , and the duration T of the state that the difference value ΔG is greater than or equal to the preset difference threshold value ΔG th is greater than or equal to the preset time threshold value T0. a pulse parameter configuration unit configured to, when judging whether the rising rate is greater than or equal to a preset rate threshold value and whether the acceleration is greater than or equal to a first preset acceleration threshold value, and when judging that the rising rate is greater than or equal to the preset rate threshold value and the acceleration is greater than or equal to the first preset acceleration threshold value, match a corresponding pulse parameter in a pre-stored blood glucose concentration-pulse parameter table in the database based on the current blood glucose concentration value.

2. The portable insulin infusion device of claim 1, wherein The non-invasive blood glucose detection module comprises: an extraction electrode for non-invasively extracting glucose in interstitial fluid based on counter-ion electro-osmosis technology; a working electrode for converting the glucose concentration extracted by the extraction electrode into a corresponding electric signal; a data processing unit electrically connected with the extraction electrode and the working electrode, configured 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 electric signal converted by the working electrode.

3. The portable insulin infusion device of claim 2, wherein, The drug loading module is a hydrogel and is connected with the extraction electrode and the working electrode.

4. The portable insulin infusion device of claim 1, wherein, The transdermal drug delivery module further comprises: The fifth judging unit is configured to obtain the records of the last N times of historical applied pulse voltage, which includes the blood glucose concentration observation value after a first specified observation period T2 after each time of applied pulse voltage, and calculate the absolute value of the deviation value between each blood glucose concentration observation value and the corresponding expected blood glucose concentration value, then calculate the mean value of the N deviation values, and judge whether the mean value is greater than or equal to a preset deviation threshold; if the mean value is greater than the preset deviation threshold, trigger the above-mentioned pulse parameter configuration unit to adjust the pulse parameter according to the mean value, wherein the relationship between the pulse parameter change amount Y and the mean value X is , 0.5 < X < 1.

5. k ​ 5. The portable insulin infusion device of claim 4, wherein, The transdermal drug delivery module further comprises: The sixth judging unit is configured to acquire a plurality of blood glucose concentration values monitored by the non-invasive blood glucose detection module within a second specified observation time period T3, and calculate a blood glucose decline rate and a decline acceleration based on the acquired plurality of blood glucose concentration values, and then identify a hypoglycemia risk level based on the decline rate and the decline acceleration, and determine a low risk if the current blood glucose decline rate is less than a preset decline rate threshold and the decline acceleration is greater than a preset decline acceleration threshold, determine a medium 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, and record a risk prompt, and determine a high risk 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, and record a risk prompt.

6. The portable insulin infusion device of claim 1, wherein, 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-glycerophosphate sodium 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.

7. The portable insulin infusion device of claim 1, wherein, Further comprising: A wireless communication module connected to the first judging unit, configured to send the current blood glucose concentration acquired by the first judging unit to a user mobile terminal; And / or, send the pulse parameters sent by the user mobile terminal to the pulse generation unit.

8. The portable insulin infusion device of claim 3, wherein, The electroporation electrode adopts a gradual fork structure; and / or, the electroporation electrode adopts a ring array arrangement.

9. The portable insulin infusion device of claim 1, wherein, The non-invasive blood glucose detection module further comprises a reference electrode.

Images