Ovarian subcutaneous continuous drug delivery system and drug delivery method

Abstract

The present invention provides an ovarian subcutaneous continuous drug supply system and a drug supply method, belonging to the technical field of drug supply systems. The system comprises a flexible substrate, a control unit, an ion introduction unit, a temperature-sensitive sustained-release layer and a microneedle array layer, the microneedle array layer comprises a plurality of microneedles, some of which are preloaded with drugs, the temperature-sensitive sustained-release layer is arranged between the flexible substrate and the microneedle array layer, the temperature-sensitive sustained-release layer comprises a plurality of drug storage cavities arranged in a honeycomb shape, each drug storage cavity outlet is provided with a temperature-sensitive polymer film, the pore size of the temperature-sensitive polymer film decreases with increasing temperature, the ion introduction unit comprises an electrode layer, the electrode layer is arranged on the outer ring of the temperature-sensitive sustained-release layer, and the control unit comprises a sensor array; in the present invention, a temperature-current dual-mode adjustment mechanism is constructed through the synergistic effect of the temperature-sensitive sustained-release layer and the ion introduction unit, so that the drug release rate can adapt to physiological changes in real time, greatly reducing the fluctuation of blood drug concentration, and significantly improving the treatment effect.

Description

Technical Field

[0001] The invention relates to the technical field of drug supply systems, and in particular to an ovarian subcutaneous continuous drug supply system and a drug supply method. Background Art

[0002] Diseases related to ovarian dysfunction, including menopausal syndrome and premature ovarian insufficiency (POI), have a core pathological mechanism of progressive attenuation of ovarian estrogen secretion, leading to an imbalance in the negative feedback regulation of the hypothalamus-pituitary-ovarian axis (HPO axis). According to statistics, about 50% of women over 40 years old worldwide suffer from menopausal symptoms, of which 15%-30% require long-term drug intervention. The current standard treatment is hormone replacement therapy (HRT), which uses exogenous supplementation of estradiol (E2), progesterone, etc. to relieve vasomotor symptoms (such as hot flashes, night sweats), neuropsychiatric symptoms (such as anxiety, depression) and osteoporosis and other systemic effects.

[0003] Traditional HRT administration routes (such as oral administration and transdermal patches) generally have pharmacokinetic (PK) regulation defects. Taking the polylactic-co-glycolic acid (PLGA) microneedle patch as an example, it uses a microneedle array to load drugs and achieves sustained release through minimally invasive penetration of the dermis. However, during treatment, the dosage of the microneedle patch cannot be adjusted, especially when the user's physiological state changes, the drug release rate cannot adapt to physiological changes in real time, resulting in large fluctuations in blood drug concentrations, which ultimately affects the treatment effect. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings and deficiencies of the prior art and to provide an ovarian subcutaneous continuous drug supply system and a drug supply method.

[0005] The technical scheme adopted by the present invention is as follows: In the first aspect, the present application provides an ovarian subcutaneous continuous drug supply system, comprising a flexible substrate, a control unit, an ion introduction unit, a temperature-sensitive sustained-release layer and a microneedle array layer, wherein the microneedle array layer comprises a plurality of microneedles, some of which are preloaded with drugs, and the temperature-sensitive sustained-release layer is arranged between the flexible substrate and the microneedle array layer, and the temperature-sensitive sustained-release layer comprises a plurality of drug storage cavities arranged in a honeycomb shape, and each of the drug storage cavity outlets is provided with a temperature-sensitive polymer film, and the pore size of the temperature-sensitive polymer film decreases with increasing temperature, and the ion introduction unit comprises an electrode layer, and the electrode layer is embedded in the flexible substrate and arranged on the outer circle of the temperature-sensitive sustained-release layer, and the control unit is integrated in the middle of the flexible substrate, which comprises a sensor array, a main control chip, a communication module and a microbattery, and the sensor array comprises a temperature sensor, a skin impedance sensor, and a drug concentration sensor, and the microbattery simultaneously powers the sensor array and the ion introduction unit through a flexible circuit.

[0006] In some embodiments, the ion introduction unit includes an insulating isolation layer, which covers the contact surface of the electrode layer with the skin, and the electrode tip is exposed on the electrode layer to contact the skin.

[0007] In some embodiments, the temperature-sensitive sustained-release layer includes an anti-reverse osmosis membrane, which covers the drug storage cavity so that the drug can only penetrate into the microneedle in one direction.

[0008] In a second aspect, the present application provides a drug supply method applied to the ovarian subcutaneous continuous drug supply system, comprising the following steps: S100: The microneedle array pierces the skin, and the preloaded drugs on some microneedles are quickly released to establish a basic blood drug concentration in the user's body; S200: The temperature-sensitive sustained-release layer passively adjusts the drug release rate according to the real-time temperature. As the user's skin temperature rises, the drug release rate slows down; S300: Under the control of the control unit, the ion introduction unit applies current at the right time and dynamically adjusts the current intensity of ion introduction according to changes in skin temperature, drug concentration and skin impedance to ensure that the blood drug concentration is maintained within the target range.

[0009] In some embodiments, step S300 includes the following steps: S310: Acquire real-time skin impedance, real-time drug concentration and real-time skin temperature; S320: Acquire dynamic current intensity based on a current intensity calculation model; S330: Execute the constraint of current intensity, set the upper limit and lower limit of current intensity, if it exceeds the upper limit, hard limit it to the upper limit and trigger an early warning, if it is lower than the lower limit, maintain the lower limit and trigger an early warning.

[0010] In some embodiments, the method further includes step S400: setting multimodal security monitoring and intervention, specifically: When the drug concentration deviation is less than 10%, only the log is recorded and the treatment is not interrupted; When the drug concentration deviation is 10%-20%, the current is reduced to the lower limit and the user is warned; If the drug concentration deviation is greater than 20%, stop taking the drug immediately; When data is lost, the average value of the most recent period is called to continue running; When communication is interrupted, data is stored locally and encrypted, and then synchronized to the cloud after recovery.

[0011] In some embodiments, in step S300, it further includes: S301: Acquire the user's heart rate variability change rate, skin conductance response density, and pulse wave transmission time change, and use principal component analysis to fuse multiple parameters to construct an emotion index; S302: updating the current intensity calculation model of step S320 based on the emotion index; S303: Establishing a user emotion prediction model based on historical data of changes in the user's heart rate variability rate, skin conductance response density, and pulse wave transmission time; S304: Based on the emotion prediction model, obtain the emotion prediction value and feed forward to the current intensity calculation model in step S302.

[0012] In some embodiments, the user's emotional state is divided into three categories: anxiety, calmness, and depression based on the emotional index. A certain period of time is regarded as a course of treatment. The changes in the user's emotional state within a course of treatment are counted, and the efficacy of the drug is judged based on the changes in the user's emotions.

[0013] In some embodiments, in step S300, a high temperature warning value is set, and if the user's skin temperature is greater than or equal to the high temperature warning value, the ion introduction function is stopped.

[0014] In some embodiments, in step S300, a drug concentration warning value is set, and if the drug concentration is greater than or equal to the drug concentration warning value, a warning is given to the user.

[0015] The beneficial effects of the present invention are as follows: In the present invention, a temperature-current dual-mode regulation mechanism is constructed through the synergistic effect of the temperature-sensitive sustained-release layer and the ion introduction unit, so that the drug release rate can adapt to physiological changes in real time, greatly reducing the fluctuation of blood drug concentration and significantly improving the treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, without paying creative labor, other drawings obtained based on these drawings still belong to the scope of the present invention.

[0017] Figure 1 This is a schematic diagram of the ovarian subcutaneous continuous drug supply system of the present invention; Figure 2 The process of the method for continuous subcutaneous drug delivery to the ovary of the present invention is as follows Figure 1 ; Figure 3 The process of the method for continuous subcutaneous drug delivery to the ovary of the present invention is as follows Figure 2 ; Figure 4 The process of the method for continuous subcutaneous drug delivery to the ovary of the present invention is as follows Figure 3 . DETAILED DESCRIPTION

[0018] The following description provides specific application scenarios and requirements of this specification, with the purpose of enabling those skilled in the art to make and use the contents of this specification. Various local modifications to the disclosed embodiments will be apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of this specification. Therefore, this specification is not limited to the embodiments shown, but to the widest scope consistent with the claims.

[0019] In the description of the present application, it should be noted that, unless otherwise expressly specified and limited, the terms "longitudinal", "transverse", "radial", "length", "width", "thickness", "up", "down", "left", "right", "front", "back", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings. These terms are mainly for better describing the present application and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific orientation, or to be constructed and operated in a specific orientation.

[0020] Secondly, the terms "first", "second" and similar words do not indicate any order, quantity or importance, but are only used to distinguish different components and should not be understood as limitations on the embodiments of the present application.

[0021] In addition, the terms "installed", "set", "provided with", "connected" and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be an internal connection between two devices, elements or components.

[0022] For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0023] The flowcharts used in this application illustrate the operations implemented by the system according to some embodiments in this specification. It should be clearly understood that the operations of the flowcharts may not be implemented in sequence. On the contrary, the operations may be implemented in reverse order or simultaneously. In addition, one or more other operations may be added to the flowchart. One or more operations may be removed from the flowchart.

[0024] Regarding the drawings of the present application, it should be clearly understood that the drawings are for illustration and description purposes only and are not intended to limit the scope of the present specification. It should also be understood that the drawings are not drawn to scale.

[0025] At present, when treating diseases related to ovarian dysfunction, drug administration routes (such as oral administration and transdermal patches) generally have pharmacokinetic (PK) regulation defects. For example, traditional microneedle patches use microneedle arrays to achieve sustained drug release through minimally invasive penetration of the dermis. However, the drug dosage of such microneedle patches cannot be adjusted, especially when the user's physiological state changes, the drug release rate cannot adapt to physiological changes in real time, resulting in large fluctuations in blood drug concentrations, which ultimately affects the treatment effect.

[0026] Based on the above problems, Figure 1 As shown, this specification provides an ovarian subcutaneous continuous drug delivery system, including a flexible substrate 1, a control unit, an ion introduction unit 2, a temperature-sensitive sustained-release layer 3 and a microneedle array layer 4.

[0027] The microneedle array layer 4 directly contacts the skin and is made of soluble hyaluronic acid or polylactic acid, etc., and can also be made of single crystal silicon, porous silicon, medical stainless steel and other materials. The needle length is generally 300-800μm. The microneedle array layer 4 includes a plurality of microneedles, and the microneedles are arranged in a regular or random array with a density of 30-50 needles per square centimeter. Some microneedles are pre-loaded with drugs, such as fast-acting drugs, which can be quickly dissolved and released after puncture.

[0028] The thermosensitive sustained-release layer 3 is arranged between the flexible substrate 1 and the microneedle array layer 4. The thermosensitive sustained-release layer 3 includes a plurality of drug storage cavities and an anti-reverse osmosis membrane arranged in a honeycomb shape. Each cavity has a diameter of 100-200 μm and is separated by polypropylene or thermosensitive hydrogel. A thermosensitive polymer membrane is arranged at the outlet of each drug storage cavity. The pore size of the membrane changes with temperature. The thermosensitive polymer membrane adopts PNIPAM, and the phase transition temperature is increased to the normal temperature range of the human body surface by copolymerization of butyl methacrylate (BMA). Generally, the normal temperature range of the human body surface is 36.5-37.2°C. Therefore, the phase transition temperature of the thermosensitive polymer membrane is ℃.

[0029] When the skin warms up due to exercise, the membrane pores shrink, reducing the risk of excessive drug release. When the body temperature is higher during the day, the release rate is automatically reduced. When the body temperature is lower at night, the release rate is increased to offset fluctuations in metabolic rate.

[0030] It can be understood that the temperature-sensitive sustained-release layer 3 and the microneedle array layer 4 can be embedded in the flexible substrate 1, and can be detachable and replaced. The temperature-sensitive sustained-release layer 3 and the microneedle array layer 4 are first assembled as drug components, wherein the drug components have different specifications, and can be divided according to drug weight, drug dosage, microneedle density, etc.

[0031] The anti-reverse osmosis membrane covers the drug storage cavity, so that the drug can only penetrate into the microneedle in one direction.

[0032] The ion introduction unit 2 includes an electrode layer and an insulating isolation layer. The electrode layer is arranged on the outer circle of the temperature-sensitive sustained-release layer 3. The electrode layer adopts a silver / silver chloride electrode. The insulating isolation layer covers the contact surface between the electrode layer and the skin. It can be a polyimide insulating film with a thickness of 5μm. Only the electrode tip is exposed to contact the skin. The electrode layer is embedded in the flexible substrate 1. Generally, a current of 0.1-0.3mA / cm² is applied. The electric field lines generated by the electrode layer vertically pass through the microneedle channel, promoting the charged drug molecules to migrate along the microneedle path.

[0033] The control unit is integrated in the middle of the flexible substrate 1, and includes a sensor array, a main control chip, a communication module and a micro battery, wherein the sensor array includes a temperature sensor, a skin impedance sensor and a drug concentration sensor.

[0034] The flexible substrate 1 is made of medical grade silicone and shape memory alloy wire, which can adapt to different wearing positions and skin curvatures to improve comfort. Its edge is provided with pressure sensitive adhesive or magnetic patch, and its top is covered with polyurethane waterproof film (IPX7 grade). The micro battery simultaneously supplies power to the sensor array and ion introduction unit 2 through the flexible circuit.

[0035] In summary, this system is used to construct a temperature-current dual-mode regulation mechanism through the synergistic effect of the temperature-sensitive sustained-release layer 3 and the ion introduction unit 2. When the skin temperature rises, the sustained-release layer automatically reduces the release rate, and at the same time, the ion introduction current increases to compensate for the decrease in penetration efficiency, thereby improving the overall release stability. In this way, the drug release rate can adapt to physiological changes in real time, greatly reducing the fluctuation of blood drug concentration and significantly improving the treatment effect.

[0036] like Figures 2 to 4 As shown, this specification also provides a method for continuous subcutaneous drug delivery to the ovary, which is mainly used to treat menopausal syndrome. The method includes the following steps: S100: The microneedle array pierces the skin with painless penetration technology, accurately piercing the stratum corneum without touching the nerve endings in the dermis, reducing the pain index during treatment. The preloaded drugs on some microneedles are quickly released to establish a basic blood drug concentration in the user's body; the basic blood drug concentration is adjusted according to individual differences of the user. Generally, when treating menopausal syndrome, the basic blood drug concentration of estradiol can be 10-50pg / mL. The basic blood drug concentration ensures that the drug quickly reaches an effective level and shortens the onset time, which is especially important for treatments that require immediate symptom relief (such as menopausal hot flashes).

[0037] S200: The temperature-sensitive sustained-release layer 3 passively adjusts the drug release rate according to the real-time temperature. As the user's skin temperature rises, the drug release rate slows down. No external power supply or complex control is required, reducing system complexity. It automatically adjusts according to temperature to adapt to environmental or physiological changes (such as changes in body temperature caused by fever or exercise) to prevent excessive drug release.

[0038] S300: Under the control of the control unit, the ion introduction unit 2 applies current at the right time and dynamically adjusts the current intensity of the ion introduction according to the changes in skin temperature, drug concentration and skin impedance to ensure that the blood drug concentration is maintained within the target range; in this way, the control accuracy is improved through multi-parameter feedback, individual differences and dynamic physiological changes are adapted, and closed-loop control maintains concentration stability, reduces fluctuations, and improves efficacy and safety.

[0039] Among them, a high temperature warning value and a drug concentration warning value are set. If the user's skin temperature is greater than or equal to the high temperature warning value, the ion introduction function is stopped; If the drug concentration is greater than or equal to the drug concentration warning value, a warning is given to the user.

[0040] S400: Setting multi-modal safety monitoring and intervention, specifically including: setting multi-level preload response and fault recovery.

[0041] In some embodiments, step S300 includes the following sub-steps: S310: Get real-time skin impedance , real-time drug concentration and real-time skin temperature ; S320: Calculate dynamic current intensity: in, is the basic current; the general ion introduction current is The penetration efficiency and skin tolerance can be balanced within the range, preferably, , mainly due to the lower This may result in insufficient penetration of macromolecular drugs (e.g., proteins) (electrophoretic efficiency < 50%). May cause skin erythema or irritation (irritation incidence >15%).

[0042] is the initial impedance; generally, , which is the typical impedance value of healthy dry skin; Alternatively, dynamic impedance calibration is performed by briefly (5 seconds) using a low current ( ) measures the initial skin impedance and dynamically updates .

[0043] is the concentration feedback gain coefficient, which is defined as the linear slope of the concentration deviation-current response, preferably, ; Alternatively, a segmented gain function can be used to improve the response speed when the concentration deviation is large. Specifically: ; Target drug concentration, such as the concentration required for estrogen replacement therapy , preferably, ; is the temperature compensation coefficient, which compensates for the decrease in the passive diffusion rate of the temperature-sensitive sustained-release layer 3 due to the increase in temperature, and maintains the total release rate stable by increasing the current. The phase transition temperature of the temperature-sensitive polymer film is set to ℃, its formula is defined as: in, is the threshold temperature, the starting temperature of the phase transition of the PNIPAM thermosensitive material, at which the pore size begins to shrink; is the slope, which is 0.05 / °C and is obtained by fitting the Arrhenius model of the PNIPAM film.

[0044] S330: current intensity constraint execution, ; If the upper limit is exceeded, the hard limit is And trigger the warning; at the same time, When limiting, switch to pulse current (such as Continue for 10 seconds, with a 5-second interval) to reduce the risk of skin irritation. Secondly, if the cumulative upper limit current time exceeds 1 hour within 24 hours, the drug should be discontinued.

[0045] If below the lower limit: Maintain And trigger an early warning.

[0046] This method, combined with heart rate variability, skin conductance, etc., can more accurately reflect the emotional state and avoid the deviation of a single parameter.

[0047] In some embodiments, in step S400, When the drug concentration deviation is less than 10%, only the log is recorded and the treatment is not interrupted; When the drug concentration deviation is 10%-20%, the current is reduced to 0.1 mA / cm² and the user is warned; When the drug concentration deviation is greater than 20%, stop taking the drug immediately and start self-test.

[0048] When data is lost, the average value of the last hour is called to continue running.

[0049] When communication is interrupted, data is stored locally and encrypted, and then synchronized to the cloud after recovery.

[0050] Through this method, the hard limit prevents the current from being too large or too small, protects the patient's safety, and the early warning mechanism notifies the abnormal situation in time. Among them, the early warning can be in the form of early warning sound, early warning light, etc.

[0051] In addition, menopausal patients often suffer from transient skin blood flow caused by autonomic nervous system disorders (local blood flow suddenly increases by 200%-300% during hot flashes), which affects the release efficiency of drug absorption.

[0052] Therefore, in some embodiments, step S300 further includes: S301: Obtaining the user's heart rate variability rate , Skin conductance response density SCR and pulse wave transmission time changes , and used principal component analysis PCA to fuse multiple parameters to construct the sentiment index; ; in, For weight distribution, preferably, ; This is the user's individualized baseline shift item, which is the user's emotional baseline value measured in a 30-minute resting state. , the general value range is -0.3-+0.3.

[0053] Heart rate variability Reflects the pressure load, which is obtained by real-time calculation using a photoplethysmography (PPG) sensor or an ECG sensor, and extracting the R wave interval after filtering; ; in, is the standard deviation of the RR interval in the current time window, It is the SDNN baseline value of an individual in a resting state.

[0054] Skin conductance response density SCR reflects the intensity of emotional arousal, and its acquisition method is to use interdigital silver / silver chloride electrodes (spacing 1.5mm) to measure skin conductance by constant voltage method (0.5V DC); ; in, is the count of nonspecific skin conductance response, and the time window is the duration of counting the number of SCRs. is the motion disturbance compensation coefficient, usually .

[0055] Pulse wave transit time changes Reflects vascular tone, and is obtained by using red light (660nm) and infrared light (880nm) LEDs simultaneously, and calculating oxygen saturation (SpO2) using the Beer-Lambert law.

[0056] ; in, It is the time difference from the current ECG R wave to the PPG foot point; is the temperature-corrected baseline PWTT value.

[0057] S302: Update the current intensity calculation model to: ; in, For emotional compensation gain, preferably, ; is the emotional sensitivity parameter, generally, ; It is understandable that the heart rate variability rate , Skin conductance response density SCR and pulse wave transmission time changes To obtain the relevant data, the relevant equipment can be integrated into the flexible substrate 1, or a wearable monitoring device such as a wristband can be connected to the control unit of the drug supply system through a communication module to provide a corresponding data stream.

[0058] S303: Based on the historical data of the user's heart rate variability change rate ∆HRV, skin conductance response density SCR, and pulse wave transmission time change ∆PWTT, a user emotion prediction model is established. The model structure is as follows: ; in, Model parameters p=3, d=1, q=2, is the Sigmoid response function, According to the signal quality and prediction error Dynamic adjustment.

[0059] The dynamic weight calculation satisfies: ; in, ∈[0,1]: signal quality index (SNR>40dB is 1, SNR<20dB is 0); : Error penalty coefficient, which suppresses the weight of abnormal parameters; : Moving average of recent forecast errors; S304: Emotion prediction value Feed forward to the current control model: ; in, is the emotion change rate gain coefficient, preferably, ; Slope compensation term: ; Through this method, feedforward control adjusts drug administration in advance to prevent concentration fluctuations caused by mood swings, improve system response speed, improve prediction accuracy based on historical data, and achieve personalized treatment. Specifically, the mood prediction model can predict the user's mood fluctuations in advance, adjust the current intensity in advance through feedforward control, and avoid blood drug concentration fluctuations caused by sudden mood changes.

[0060] In some embodiments, the user's emotional state is divided into three levels: anxiety, calmness, and depression based on the emotional index. A certain period of time is taken as a course of treatment, such as a week or a month. The changes in the user's emotional state within a course of treatment are counted, and the efficacy of the drug is judged based on the changes in the user's emotions. It can be understood that the emotional index can be used as one of the criteria for judging the efficacy of the drug, but it is generally not entirely based on this. In general, based on the proportion of anxiety, calmness, and depression of the user in a course of treatment, when the proportion of the time when the user's emotions are calm reaches the standard value, it means that the drug efficacy is effective, and the dosage can be lowered or the drug administration efficiency can be reduced; and when the proportion of the time when the user's emotions are anxious or depressed reaches the limit value, it means that the drug efficacy is ineffective, and it is necessary to re-diagnose, adjust the drug, increase the drug dosage, etc., and finally form a closed-loop system to ensure the high efficiency of the treatment.

[0061] In summary, after reading this detailed disclosure, those skilled in the art will appreciate that the foregoing detailed disclosure may be presented only by way of example and may not be restrictive. Although not explicitly stated herein, those skilled in the art will appreciate that the requirements of this application encompass various reasonable changes, improvements and modifications to the embodiments. These changes, improvements and modifications are intended to be proposed by the present application and are within the spirit and scope of the exemplary embodiments of the present application.

[0062] In addition, it should be understood that in the foregoing description of the embodiments of the present application, in order to help understand a feature and for the purpose of simplifying the present application, the present application combines various features in a single embodiment, drawing or its description. However, this does not mean that the combination of these features is necessary. When reading the present application, it is entirely possible for a person skilled in the art to mark out a part of the devices as a separate embodiment. In other words, the embodiments in the present application can also be understood as the integration of multiple secondary embodiments. This is also true when the content of each secondary embodiment is less than all the features of a single aforementioned disclosed embodiment.

[0063] Finally, it should be understood that the embodiments of the application disclosed herein are explanations of the principles of the embodiments of the present application. Other modified embodiments are also within the scope of the present application. Therefore, the embodiments disclosed in the present application are merely examples and not limitations. Those skilled in the art can adopt alternative configurations according to the embodiments in the present application to implement the application in the present application. Therefore, the embodiments of the present application are not limited to the embodiments accurately described in the application.

Claims

1. Ovarian subcutaneous continuous drug supply system, characterized in that: It includes a flexible substrate, a control unit, an ion introduction unit, a temperature-sensitive sustained-release layer and a microneedle array layer. The microneedle array layer includes a plurality of microneedles, some of which are preloaded with drugs. The temperature-sensitive sustained-release layer is arranged between the flexible substrate and the microneedle array layer. The temperature-sensitive sustained-release layer includes a plurality of drug storage cavities arranged in a honeycomb shape. Each drug storage cavity outlet is provided with a temperature-sensitive polymer film. The pore size of the temperature-sensitive polymer film decreases with increasing temperature. The ion introduction unit includes an electrode layer, which is embedded in the flexible substrate and arranged on the outer circle of the temperature-sensitive sustained-release layer. The control unit is integrated in the middle of the flexible substrate. It includes a sensor array, a main control chip, a communication module and a microbattery. The sensor array includes a temperature sensor, a skin impedance sensor and a drug concentration sensor. The microbattery simultaneously supplies power to the sensor array and the ion introduction unit through a flexible circuit.

2. The ovarian subcutaneous continuous drug supply system according to claim 1, characterized in that: The ion introduction unit comprises an insulating isolation layer, which covers the contact surface between the electrode layer and the skin, and the electrode tip is exposed on the electrode layer to contact the skin.

3. The ovarian subcutaneous continuous drug supply system according to claim 1, characterized in that: The temperature-sensitive sustained-release layer includes an anti-reverse osmosis membrane, which covers the drug storage cavity, so that the drug can only penetrate into the microneedle in one direction.

4. A drug supply method for the ovarian subcutaneous continuous drug supply system according to any one of claims 1 to 3, characterized in that: The steps include: S100: The microneedle array pierces the skin, and the preloaded drugs on some microneedles are quickly released to establish a basic blood drug concentration in the user's body; S200: The temperature-sensitive sustained-release layer passively adjusts the drug release rate according to the real-time temperature. As the user's skin temperature rises, the drug release rate slows down; S300: Under the control of the control unit, the ion introduction unit applies current at the right time and dynamically adjusts the current intensity of ion introduction according to changes in skin temperature, drug concentration and skin impedance to ensure that the blood drug concentration is maintained within the target range.

5. The method for continuous subcutaneous drug delivery to the ovary according to claim 4, characterized in that: In step S300, the following steps are included: S310: Acquire real-time skin impedance, real-time drug concentration and real-time skin temperature; S320: Acquire dynamic current intensity based on a current intensity calculation model; S330: Execute the constraint of current intensity, set the upper limit and lower limit of current intensity, if it exceeds the upper limit, hard limit it to the upper limit and trigger an early warning, if it is lower than the lower limit, maintain the lower limit and trigger an early warning.

6. The method for continuous subcutaneous drug delivery to the ovary according to claim 5, characterized in that: The method further includes step S400: setting multi-modal security monitoring and intervention, specifically: When the drug concentration deviation is less than 10%, only the log is recorded and the treatment is not interrupted; When the drug concentration deviation is 10%-20%, the current is reduced to the lower limit and the user is warned; If the drug concentration deviation is greater than 20%, stop taking the drug immediately; When data is lost, the average value of the most recent period is called to continue running; When communication is interrupted, data is stored locally and encrypted, and then synchronized to the cloud after recovery.

7. The method for continuous subcutaneous drug delivery to the ovary according to claim 4, characterized in that: In step S300, it also includes: S301: Acquire the user's heart rate variability change rate, skin conductance response density, and pulse wave transmission time change, and use principal component analysis to fuse multiple parameters to construct an emotion index; S302: updating the current intensity calculation model of step S320 based on the emotion index; S303: Establishing a user emotion prediction model based on historical data of changes in the user's heart rate variability rate, skin conductance response density, and pulse wave transmission time; S304: Based on the emotion prediction model, obtain the emotion prediction value and feed forward to the current intensity calculation model in step S302.

8. The method for continuous subcutaneous drug delivery to the ovary according to claim 7, characterized in that: Based on the emotional index, the user's emotional state is divided into three categories: anxiety, calmness and depression. A certain period of time is regarded as a course of treatment. The changes in the user's emotional state within a course of treatment are counted, and the efficacy of the drug is judged based on the changes in the user's emotions.

9. The method for continuous subcutaneous drug delivery to the ovary according to claim 4, characterized in that: In step S300, a high temperature warning value is set, and if the user's skin temperature is greater than or equal to the high temperature warning value, the ion introduction function is stopped.

10. The method for continuous subcutaneous drug delivery to the ovary according to claim 9, characterized in that: In step S300, a drug concentration warning value is set, and if the drug concentration is greater than or equal to the drug concentration warning value, a warning is given to the user.

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