A drug delivery device based on the brain extracellular space approach

Abstract

The application discloses a drug delivery device based on brain extracellular space pathway, and relates to the technical field of medical devices.The deformable characteristic of the flexible silicone probe reduces the puncture resistance, and in cooperation with the hydrophilic coating, the physical stimulation to the fragile gap structure of the old brain is significantly reduced.The device automatically adjusts the drug delivery behavior through real-time sensing and closed-loop control when encountering tissue pressure fluctuation, thereby avoiding local edema or microscopic tearing caused by traditional rigid probes.A pressure rate mapping model is designed based on the biomechanical characteristics of the old brain, so that the device can autonomously respond to changes in the gap environment and automatically reduce the speed when the pressure exceeds the threshold value, without the need for manual intervention by the doctor based on experience, thereby reducing abnormal drug distribution caused by operation delay or misjudgment.The mechanism is particularly suitable for the dynamic instability of the old brain ECS, and ensures that the parameters and physiological state are matched during the whole treatment.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a drug delivery device based on the extracellular space pathway of brain cells. Background Technology

[0002] Extracellular space drug delivery devices are mainly used to treat neurodegenerative diseases, such as Parkinson's disease or Alzheimer's disease. These devices deliver drugs directly to brain tissue, bypassing the blood-brain barrier and increasing the concentration of drugs in the target area. Elderly patients are a high-risk group for neurological diseases, and the extracellular space structure of their brains changes with age, making this route an important clinical option. However, the brain tissue of the elderly exhibits unique microenvironment characteristics, such as reduced space volume and increased mechanical fragility, which poses specific requirements for drug delivery operations.

[0003] Newer drug delivery devices, such as intelligent convection-enhanced drug delivery systems or imaging-guided injection devices, face challenges in treating elderly patients. The device parameter settings rely on fixed patterns and cannot dynamically adapt to real-time changes in the spaces between brain tissues. During operation, they may cause local structural damage or uneven drug distribution, increasing treatment risks. The lack of a real-time feedback mechanism means that doctors need to manually adjust the devices based on experience, resulting in low efficiency in dealing with the microscopic fragility of the elderly brain.

[0004] Existing technologies, such as adaptive drug delivery devices with integrated sensors, attempt to introduce environmental monitoring functions to optimize parameter settings. Other devices collect interbrain space data through miniature sensors to assist doctors in calibration. However, these solutions are still insufficient to cope with the rapid changes in the brain in the elderly, rely on human intervention, and cannot completely eliminate operational uncertainties. Summary of the Invention

[0005] In view of the aforementioned existing problems, the present invention is proposed.

[0006] This invention provides a drug delivery device based on the extracellular space pathway of brain cells, which solves the problems of fragile and vulnerable ECS structures in the elderly, and the high risk of tissue damage and poor controllability of drug distribution caused by the fixed parameters and reliance on manual operation of existing drug delivery devices.

[0007] To solve the above-mentioned technical problems, the present invention provides the following technical solution:

[0008] This invention provides a drug delivery device based on the extracellular space pathway in the brain, comprising:

[0009] The flexible drug delivery probe is made of biocompatible silicone and includes a deformable needle body and internal microchannels, wherein the needle body has a diameter of 20-50 micrometers.

[0010] A MEMS piezoresistive pressure sensor array is arranged on the surface of the needle body with a spacing of 50-100 micrometers to detect the real-time pressure in the extracellular space of brain cells and output pressure signals.

[0011] Closed-loop controller, including:

[0012] The signal receiving module is electrically connected to the pressure sensor array;

[0013] The embedded processing module is preloaded with a pressure-rate mapping model and converts pressure signals into drug delivery rate commands.

[0014] The instruction output module is connected to the embedded processing module;

[0015] The piezoelectric ceramic driven micropump is connected to the command output module through a drive circuit. It adjusts the drug flow rate according to the drug administration rate command, with a flow rate adjustment accuracy of ±0.05 μL / min.

[0016] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain cells described in this invention, the flexible drug delivery probe has a nano-scale hydrophilic coating on its needle surface, with a coating thickness of 100-200 nanometers.

[0017] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the present invention, wherein: the MEMS piezoresistive pressure sensor array covers more than 80% of the needle length, and the effective detection area of ​​a single sensor is 30×30 micrometers.

[0018] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain as described in this invention, wherein: the pressure-rate mapping model performs:

[0019] When three consecutive pressure signal values ​​exceed the 20-100 Pascal threshold, a rate reduction command is generated.

[0020] When the pressure signal value is below 70% of the threshold, a rate increase command is generated;

[0021] The threshold was set based on the Young's modulus range of 0.5-2 kPa for aged brain tissue.

[0022] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain cells described in this invention, the sampling interval of the three consecutive pressure signal values ​​is 0.1-0.5 seconds, corresponding to the elastic response time of brain tissue.

[0023] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain as described in this invention, it further includes an optical positioning module.

[0024] A near-infrared emitter is fixed to the base of the flexible drug delivery probe;

[0025] An optical receiver captures reflected signals and generates three-dimensional coordinate data of the probe.

[0026] The closed-loop controller receives three-dimensional coordinate data and triggers a pause command when the coordinate offset is greater than 0.2 mm.

[0027] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain cells described in this invention, the optical positioning module has a positioning accuracy of 50 micrometers and an operating wavelength range of 800-900 nanometers.

[0028] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain cells described in this invention, the piezoelectric ceramic driven micropump has a driving voltage of 5-12 volts and a response time of <10 milliseconds.

[0029] As a preferred embodiment of the drug delivery device based on the extracellular space pathway of the brain cells described in this invention, it further includes a sterile sealed outer shell covering the flexible drug delivery probe and pressure sensor array;

[0030] The probe base is equipped with a detachable radio frequency positioning mark;

[0031] The markers are registered with the coordinate system of the MRI or CT imaging equipment.

[0032] The beneficial effects of this invention are:

[0033] 1. The deformable properties of the flexible silicone probe in this invention reduce puncture resistance. Combined with the hydrophilic coating on the surface, it significantly reduces physical stimulation to the fragile interstitial structures of the elderly brain. Furthermore, when encountering fluctuations in tissue pressure, it automatically adjusts the drug delivery behavior through real-time sensing and closed-loop control, avoiding local edema or microscopic tearing caused by traditional rigid probes.

[0034] 2. The present invention is based on a pressure-rate mapping model designed according to the biomechanical characteristics of the elderly brain, which enables the device to respond autonomously to changes in the interstitial environment. When the pressure exceeds the threshold, it automatically reduces the speed without the need for manual intervention by doctors based on experience, reducing abnormal drug distribution caused by operational delays or misjudgments. This mechanism is particularly suitable for the dynamic instability of the elderly brain ECS, ensuring that the parameters are matched with the physiological state throughout the treatment process.

[0035] 3. The present invention integrates an optical positioning module to provide real-time probe coordinate feedback. When the micro-displacement exceeds the safety tolerance, drug administration is immediately suspended. Combined with the high-precision flow control of the micro-pump, drug leakage to non-target areas is prevented, reducing the risk of neurotoxicity to sensitive brain regions.

[0036] 4. The design of the sterile shell and radio frequency positioning mark of this invention allows the device to be directly registered with the hospital's existing imaging equipment, simplifying the preoperative planning process. Doctors do not need to learn complicated operations, and can monitor the drug delivery route through the standard imaging interface, thereby improving the surgical efficiency of elderly patients.

[0037] 5. This invention integrates the sensing, decision-making, and execution modules into an independent closed-loop system. Its adaptive mechanism covers the unique variations in the age-related brain, such as reduced interstitial volume and decreased elasticity, providing more reliable device support for the treatment of neurodegenerative diseases. Attached Figure Description

[0038] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the following description of the embodiments will be briefly introduced. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0039] Figure 1 This is a structural diagram of a drug delivery device based on the extracellular space pathway in brain cells.

[0040] Figure 2 This is a cross-sectional view of a drug delivery device based on the extracellular space pathway in the brain.

[0041] Figure 3 This is a schematic diagram of a closed-loop controller for a drug delivery device based on the extracellular space pathway in the brain.

[0042] Figure 4 This is a structural diagram of the optical positioning module of a drug delivery device based on the extracellular space pathway of brain cells.

[0043] Legend:

[0044] 1. Sterile sealed housing; 2. Probe base; 3. Needle body; 4. MEMS piezoresistive pressure sensor array; 5. Piezoelectric ceramic driven micropump; 6. Closed-loop controller; 7. Optical positioning module; 101. Engaging groove; 102. Engaging block; 103. Radio frequency positioning mark; 11. Probe microchannel. Detailed Implementation

[0045] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0046] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0047] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0048] Reference Figures 1-4 This embodiment provides a drug delivery device based on the extracellular space pathway of brain cells, comprising:

[0049] The flexible drug delivery probe is made of biocompatible silicone and includes a deformable needle body 3 and internal microchannels 11. The needle body has a diameter of 20-50 micrometers.

[0050] MEMS piezoresistive pressure sensor array 4 is set on the needle surface with a spacing of 50-100 micrometers to detect the real-time pressure in the extracellular space of brain cells and output pressure signals.

[0051] The closed-loop controller 6 includes:

[0052] The signal receiving module is electrically connected to the pressure sensor array;

[0053] The embedded processing module is preloaded with a pressure-rate mapping model and converts pressure signals into drug delivery rate commands.

[0054] The instruction output module connects to the embedded processing module;

[0055] The piezoelectric ceramic driven micro pump 5 is connected to the command output module through the drive circuit. It adjusts the drug flow rate according to the drug administration rate command, and the flow rate adjustment accuracy is ±0.05 μL / min.

[0056] The flexible drug delivery probe has a nanoscale hydrophilic coating on its needle surface, with a coating thickness of 100-200 nanometers.

[0057] The MEMS piezoresistive pressure sensor array 4 covers more than 80% of the needle length, and the effective detection area of ​​a single sensor is 30×30 micrometers.

[0058] Pressure-rate mapping model execution:

[0059] When three consecutive pressure signal values ​​exceed the 20-100 Pascal threshold, a rate reduction command is generated.

[0060] When the pressure signal value is below 70% of the threshold, a rate increase command is generated.

[0061] The threshold was set based on the Young's modulus range of 0.5-2 kPa for aged brain tissue.

[0062] The sampling interval for three consecutive pressure signal values ​​is 0.1-0.5 seconds, corresponding to the elastic response time of brain tissue.

[0063] It also includes optical positioning module 7:

[0064] A near-infrared emitter is fixed to the base of a flexible drug delivery probe;

[0065] An optical receiver captures reflected signals and generates three-dimensional coordinate data of the probe.

[0066] The closed-loop controller 6 receives three-dimensional coordinate data and triggers a pause command when the coordinate offset is greater than 0.2 mm.

[0067] The positioning accuracy of the optical positioning module 7 is 50 micrometers, and the working wavelength range is 800-900 nanometers.

[0068] The piezoelectric ceramic driven micro pump 5 has a driving voltage of 5-12 volts and a response time of <10 milliseconds.

[0069] It also includes a sterile sealed housing 1, which encapsulates a flexible drug delivery probe and a pressure sensor array;

[0070] The probe base 2 is provided with a detachable radio frequency positioning mark 103;

[0071] Register the markers with the coordinate system of the MRI or CT imaging equipment.

[0072] The probe base 2 has a locking groove 101 on its side, and a locking block 102 is locked in the locking groove 101. The radio frequency positioning mark 103 is set on the locking block 102. The locking block 102 is locked in the locking groove 101 to realize the rapid installation of the radio frequency positioning mark 103.

[0073] The flexible drug delivery probe is made of biocompatible materials. Its needle body is deformable and has microchannels inside. The surface of the needle body is treated with a special coating to improve performance. A pressure sensor array is integrated on the probe surface to detect changes in intercerebral pressure in real time and output relevant signals. A closed-loop controller is connected to the sensor array and contains multiple modules to process signals and generate control commands. A micropump adjusts the drug flow rate based on the commands to ensure accurate drug delivery.

[0074] Furthermore, its functionality is enhanced through a coating, and the sensor array layout covers the probe body area to improve detection reliability. The closed-loop controller's algorithm model dynamically adjusts the dosing rate based on pressure signals, including the generation logic for up or down commands. This model, combined with a specific sampling mechanism, ensures timely response. It also integrates an optical positioning module, containing transmitting and receiving components, for real-time tracking of the probe position and triggering protective actions when the deviation exceeds the safe range. The positioning module has high precision characteristics to meet clinical needs, and the micro-pump design ensures rapid response capability. A sterile sealed shell covers the core components, and the shell is marked for registration with external devices to improve operational compatibility.

[0075] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A drug delivery device based on the extracellular space pathway in the brain, characterized in that, include: The flexible drug delivery probe is made of biocompatible silicone and includes a deformable needle body and internal microchannels, wherein the needle body has a diameter of 20-50 micrometers. A MEMS piezoresistive pressure sensor array is arranged on the surface of the needle body with a spacing of 50-100 micrometers to detect the real-time pressure in the extracellular space of brain cells and output pressure signals. Closed-loop controller, including: The signal receiving module is electrically connected to the pressure sensor array; The embedded processing module is preloaded with a pressure-rate mapping model and converts pressure signals into drug delivery rate commands. The instruction output module is connected to the embedded processing module; The piezoelectric ceramic driven micropump is connected to the command output module through a drive circuit, and adjusts the drug flow rate according to the drug administration rate command.

2. The drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, The flexible drug delivery probe has a nanoscale hydrophilic coating on its needle surface, with a coating thickness of 100-200 nanometers.

3. The drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, The MEMS piezoresistive pressure sensor array covers more than 80% of the needle length, and the effective detection area of ​​a single sensor is 30×30 micrometers.

4. The drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, The pressure-rate mapping model is executed as follows: When three consecutive pressure signal values ​​exceed the 20-100 Pascal threshold, a rate reduction command is generated. When the pressure signal value is below 70% of the threshold, a rate increase command is generated; The threshold was set based on the Young's modulus range of 0.5-2 kPa for aged brain tissue.

5. A drug delivery device based on the extracellular space pathway as described in claim 4, characterized in that, The sampling interval for the three consecutive pressure signal values ​​is 0.1-0.5 seconds, corresponding to the elastic response time of brain tissue.

6. A drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, It also includes an optical positioning module: A near-infrared emitter is fixed to the base of the flexible drug delivery probe; An optical receiver captures reflected signals and generates three-dimensional coordinate data of the probe. The closed-loop controller receives three-dimensional coordinate data and triggers a pause command when the coordinate offset is greater than 0.2 mm.

7. A drug delivery device based on the extracellular space pathway as described in claim 6, characterized in that, The optical positioning module has a positioning accuracy of 50 micrometers and an operating wavelength range of 800-900 nanometers.

8. A drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, The piezoelectric ceramic driven micropump has a driving voltage of 5-12 volts and a response time of <10 milliseconds.

9. A drug delivery device based on the extracellular space pathway as described in claim 1, characterized in that, It also includes a sterile sealed housing that encloses the flexible drug delivery probe and pressure sensor array; The probe base is equipped with a detachable radio frequency positioning mark; The markers are registered with the coordinate system of the MRI or CT imaging equipment.

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