Skull drug injection interface for slow-release drug delivery of deep brain tissue

Abstract

The invention relates to the technical field of medical materials, and discloses a skull drug injection interface for slow-release drug delivery of deep brain tissue, the skull drug injection interface comprises a titanium alloy matrix and a liquid storage port arranged on one side of the titanium alloy matrix, and one side of the liquid storage port close to the titanium alloy matrix is fixedly connected with an outer ring body; the side, close to the titanium alloy base body, of the outer ring body is fixedly connected with a clamping ring, and the side, away from the liquid containing opening, of the titanium alloy base body is provided with a flow dividing valve. According to the invention, preliminary positioning with the titanium alloy base body is realized through the nested structure of the inner ring body and the outer ring body, and then the clamping ring is accurately clamped into the clamping groove, so that the double fixing effects of axial limiting and circumferential rotation prevention are achieved. By means of the structural design, after the connector is implanted into the cranium of a patient, the connection stability of all parts is remarkably improved, and the problem of connection looseness and even breakage caused by physiological activities or external force disturbance after implantation is effectively solved.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a cranial drug injection interface for sustained-release drug delivery to deep brain tissue. Background Technology

[0002] A cranial drug delivery interface is a medical device implanted through the skull to precisely deliver drugs to deep brain tissue and achieve sustained release, primarily addressing the challenge of the blood-brain barrier (BBB) ​​preventing drugs from reaching the brain. This type of interface provides an alternative to traditional intravenous injection, offering higher drug concentrations, fewer systemic side effects, longer duration of action, and more precise targeting. However, it also carries significant risks: craniotomy requires the removal of a portion of the bone flap to expose brain tissue, leading to a high incidence of cerebral edema; the integrity of the meninges is easily compromised, potentially inducing bacterial meningitis. The reservoir implantation technique, developed in the 1990s, enables ventricular targeted therapy and can be reused long-term, reducing the number of punctures. However, it also has some drawbacks: the duration of single-dose administration is short, the surgery is expensive, and it places a significant burden on patients.

[0003] However, in actual use, the above-mentioned cranial drug injection interface is prone to problems such as displacement or poor contact of the interface components due to prolonged use by patients. This can lead to drug delivery interruption or damage to brain tissue. On the other hand, it lacks drug delivery capabilities and makes it difficult to achieve simultaneous local controlled release of different drugs, which restricts the safe application of neuromodulation technology. Therefore, we propose a cranial drug injection interface for sustained-release drug delivery to deep brain tissue. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] To address the shortcomings of existing technologies, this invention provides a cranial drug injection interface for sustained-release drug delivery to deep brain tissue, solving the problems of interface component displacement and difficulty in achieving simultaneous local controlled release of different drugs.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution: a cranial drug injection interface for sustained-release drug delivery to deep brain tissue, comprising a titanium alloy substrate and a liquid inlet located on one side of the titanium alloy substrate. An outer ring is fixedly connected to the side of the liquid inlet near the titanium alloy substrate, and the outer ring is fixedly fitted to the titanium alloy substrate. A snap-fit ​​ring is fixedly connected to the side of the outer ring near the titanium alloy substrate. A snap-fit ​​groove is formed on the side of the titanium alloy substrate near the snap-fit ​​ring, and the snap-fit ​​ring is placed in the snap-fit ​​groove and fixedly fitted to it. An inner ring is fixedly fitted to the inner wall of the titanium alloy substrate away from the outer ring, and the side of the inner ring near the liquid inlet is fixedly connected to the liquid inlet. A diversion valve is installed on the side of the titanium alloy substrate away from the liquid inlet, and the side of the titanium alloy substrate near the diversion valve is placed inside the diversion valve and fixedly connected to it.

[0008] Preferably, a biological pad is provided on the side of the liquid inlet away from the outer ring body, and a gasket ring is fixedly connected to the side of the biological pad near the liquid inlet, and the gasket ring is placed inside the liquid inlet and fixedly attached to the liquid inlet.

[0009] Preferably, the diverter valve has an inlet valve port fixedly installed on the side of the titanium alloy substrate, and the inlet valve port extends into the interior of the titanium alloy substrate and is fixedly connected thereto.

[0010] Preferably, four sets of drug delivery tubes are inserted and installed circumferentially on the side of the diversion valve away from the titanium alloy substrate, so as to accurately deliver the drug to a specific target area deep in the brain and achieve precise treatment in different areas of the brain.

[0011] Preferably, the drug delivery tube has an ultra-fine inner diameter and ultra-high bending fatigue life, adopts a three-layer composite structure, with an inner layer of hydrophilic polyurethane coating to reduce flow resistance, a middle layer of medical-grade stainless steel or nickel-titanium alloy braided mesh to resist bending, and an outer layer of tantalum powder-containing silicone or PEEK to enhance radioactivity. The end is designed with a multi-stage drug release head, and the flow control accuracy needs to reach the microliter per minute level. It is dynamically coupled with a diverter valve through a conical self-sealing interface to achieve millimeter-level targeted drug delivery and multi-channel timing control in brain tissue.

[0012] Preferably, the main body of the diversion valve is made of PEEK or titanium alloy, and the diaphragm material in the channel is one or more of medical silicone, thermoplastic polyurethane, and expanded polytetrafluoroethylene. The entire surface of the channel is heparinized. The diversion valve adjusts the flow rate and release sequence of each channel as needed according to real-time biological signals. Its control algorithm can control the flow error within ±1, avoiding local drug overload.

[0013] Preferably, the bio-pad is composed of one or more of a titanium / silicone implant shell, a titanium / PEEK skull plate, and a collagen matrix. The interface between the bio-pad and the titanium alloy matrix is ​​coated with photocurable bone cement or a bioactive photocurable composite material, and the shear strength after curing is greater than 18 MPa.

[0014] Preferably, the titanium alloy matrix includes a flexible microelectrode array and a cortical electroencephalogram sensor modified with gold nanowires. The electrode point temperature-sensitive sustained-release unit inside the titanium alloy matrix is ​​composed of a microfluidic cooling layer made of chitosan / polyN-isopropylacrylamide hydrogel, and has built-in serpentine microchannels and Peltier cooling sheets.

[0015] In summary, the technical effects and advantages of this invention are as follows:

[0016] 1. In this invention, a biocompatible bio-pad is fitted to the top of the titanium alloy substrate. The bio-pad, facing the titanium alloy substrate, is integrally formed with an outer ring and an inner ring, arranged concentrically. The inner ring is embedded in the internal cavity of the titanium alloy substrate, forming a tightly fitted and fixed structure with the inner wall of the substrate. An annular locking ring is fixedly connected to the end face of the outer ring near the titanium alloy substrate. Correspondingly, an annular locking groove precisely matching the size of the locking ring is formed on the top edge of the titanium alloy substrate. During interface assembly, the nested structure of the inner and outer rings achieves initial positioning with the titanium alloy substrate. Subsequently, the locking ring precisely engages in the locking groove, forming a dual fixation effect of axial limiting and circumferential anti-rotation. This structural design significantly improves the connection stability of each component after the interface is implanted into the patient's cranium, effectively avoiding loosening or even breakage of the connection due to physiological activities or external disturbances after implantation, greatly improving the clinical safety of the device.

[0017] 2. In this invention, the bottom of the titanium alloy substrate and the diversion valve are integrated. The titanium alloy substrate is embedded and fixed in the top slot of the diversion valve through precision machining, forming a seamless integrated structure. This design effectively isolates intracranial fluids such as cerebrospinal fluid from direct contact with key components of the diversion valve, preventing valve failure caused by fluid erosion. Furthermore, the integrated structure provides a stable carrier for multi-pathway drug delivery, enabling precise simultaneous local controlled release and independent dose adjustment of multiple drugs. Compared to traditional separate structures, this not only simplifies clinical procedures but also improves the accuracy and reliability of drug delivery. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the overall structure of a cranial drug injection interface for sustained-release drug delivery to deep brain tissue according to the present invention.

[0019] Figure 2This is a schematic diagram of the segmented overall structure of a cranial drug injection interface for sustained-release drug delivery to deep brain tissue according to the present invention.

[0020] Figure 3 This is a schematic diagram of the overall structure of the biological pad and the liquid inlet of the present invention;

[0021] Figure 4 This is a bottom view schematic diagram of the overall structure of the titanium alloy matrix and the diversion valve of the present invention;

[0022] Figure 5 This is a top view schematic diagram of the overall structure of the titanium alloy matrix and the diversion valve of the present invention.

[0023] In the diagram: 1. Biological pad; 101. Pad ring; 2. Liquid inlet; 201. Outer ring; 202. Inner ring; 203. Snap-fit ​​ring; 3. Titanium alloy substrate; 301. Snap-fit ​​groove; 4. Diverter valve; 401. Liquid inlet valve port; 402. Drug delivery tube. Detailed Implementation

[0024] 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 embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] refer to Figures 1-5 The skull drug delivery interface shown includes a titanium alloy substrate 3 and a liquid inlet 2 located on one side of the titanium alloy substrate 3. A specific embodiment is shown below:

[0026] Example 1

[0027] An annular outer ring 201 is fixedly connected to the end face of the inlet 2 near the titanium alloy substrate 3. This outer ring 201 is tightly fitted and fixed to the outer side wall of the titanium alloy substrate 3. A raised annular retaining ring 203 is integrally formed on the side of the outer ring 201 facing the titanium alloy substrate 3. Correspondingly, an annular retaining groove 301, precisely matching the size of the retaining ring 203, is formed on the outer wall of the titanium alloy substrate 3. The retaining ring 203 is embedded in the retaining groove 301 to form an axial limiting and fixing mechanism. Simultaneously, an inner ring 202 is tightly fitted and fixed to the inner side of the titanium alloy substrate 3. The top of the inner ring 202 is fixedly connected to the bottom of the inlet 2, forming an "inner-outer" dual positioning structure. This design, through the synergistic constraint of the inner ring 202 and the outer ring 201, significantly improves the connection stability between the inlet 2 and the titanium alloy substrate 3. After implantation into the cranium, it effectively prevents connection loosening or breakage due to physiological activities, greatly improving the clinical safety of the device.

[0028] Example 2

[0029] The titanium alloy matrix 3 integrates core functional components, including a flexible microelectrode array and a gold nanowire-modified cortical electroencephalography (EEG) sensor, enabling real-time acquisition of intracranial electrophysiological signals. Simultaneously, the matrix embeds a thermosensitive sustained-release electrode unit. This unit uses a chitosan / poly(N-isopropylacrylamide) composite hydrogel as its core functional layer, combined with an internal serpentine microfluidic channel and a Peltier cooling pad to form a microfluidic cooling system. Through temperature signal feedback and precise control of the cooling pad, synergistic linkage between drug release rate and electrophysiological monitoring can be achieved, providing data support for personalized drug delivery.

[0030] Example 3

[0031] The bottom of the titanium alloy substrate 3 is embedded and fixedly connected to the diversion valve 4. The lower end of the titanium alloy substrate 3 is integrally embedded into a pre-set groove on the top of the diversion valve 4, forming a gapless fit. A liquid inlet valve 401 is provided on the side of the diversion valve 4 closest to the titanium alloy substrate 3. The top of the liquid inlet valve 401 extends into the internal cavity of the titanium alloy substrate 3 and is sealed and fixed, ensuring the airtightness of the drug delivery pathway. Four sets of drug delivery tubes 402 are evenly distributed circumferentially on the end face of the diversion valve 4 away from the titanium alloy substrate 3. All delivery tubes are fixed by a precision insertion process. This design can guide different drugs to specific target areas deep in the brain, achieving simultaneous and precise treatment of multiple lesions, significantly improving the targeting and flexibility of drug delivery.

[0032] Example 4

[0033] The main body of the shunt valve 4 is made of biocompatible PEEK material or titanium alloy. Its internal channel isolation structure uses one or more composites of medical-grade silicone, thermoplastic polyurethane, or expanded polytetrafluoroethylene as the diaphragm material, effectively achieving isolated delivery of different drugs. To improve blood compatibility, the surfaces of all channels inside the shunt valve are heparinized, significantly reducing the risk of thrombosis. This shunt valve is equipped with an intelligent controlled-release system that dynamically adjusts the drug flow rate and release sequence of each channel based on real-time acquired biological signals. Its core control algorithm can control the flow error within ±1%, fundamentally avoiding toxic side effects caused by local drug concentration overload.

[0034] Example 5

[0035] The drug delivery tube 402 employs a three-layer composite structure design to meet the stringent requirements of intracranial drug delivery: the inner layer is coated with a hydrophilic polyurethane coating, which significantly reduces flow resistance during drug delivery and avoids drug residue; the middle layer is a medical-grade stainless steel or nickel-titanium alloy braided mesh, giving the delivery tube an ultra-high bending fatigue life, adapting to the complex physiological environment of the intracranial cavity and the need for long-term implantation; the outer layer uses silicone or PEEK material containing tantalum powder, which significantly enhances imaging contrast and facilitates postoperative positioning and monitoring. The end of the delivery tube is designed with a multi-stage drug release head, with flow control accuracy down to the μL / min level, and achieves dynamic coupling with the diverter valve 4 through a conical self-sealing interface, ensuring both connection sealing and enabling millimeter-level precision targeted drug delivery and multi-channel release timing control within brain tissue.

[0036] Example 6

[0037] A bio-pad 1 is fitted at the top of the inlet 2, away from the outer ring 201. An annular gasket ring 101 is integrally formed on the side of the bio-pad 1 facing the inlet 2. The gasket ring 101 is embedded in the top opening of the inlet 2 and tightly fitted and fixed. The substrate of the bio-pad 1 is made of one or more composite materials selected from titanium / silicone composite implant shell, titanium / PEEK skull plate, or collagen matrix, possessing both good biocompatibility and structural strength. To enhance the fixation effect, the interface between the bio-pad 1 and the titanium alloy substrate 3 is coated with light-cured bone cement or bioactive light-cured composite material. The shear strength of the cured material can stably exceed 18 MPa, ensuring structural stability for long-term use after implantation.

[0038] Working principle of this invention:

[0039] First, the biological pad 1 serves as the contact interface between the device and the skull. Its material is selected from titanium / silicone composite shell, titanium / PEEK skull plate or collagen matrix, which can be adapted to the physiological environment of the skull. The pad ring 101 at the bottom of the pad is embedded in the liquid inlet 2 to form a preliminary positioning. At the same time, the interface between the biological pad and the titanium alloy substrate 3 is coated with light-cured bone cement or bioactive composite material. After curing, the shear strength exceeds 18MPa, ensuring a firm interface connection.

[0040] Secondly, the connection between the liquid inlet 2 and the titanium alloy substrate 3 adopts a "dual constraint" design: the inner ring 202 is fixed to the inner wall of the titanium alloy substrate, while the outer ring 201 is fixed to the outer wall, and its bottom locking ring 203 is precisely engaged in the locking groove 301 of the titanium alloy substrate, forming a mechanical locking effect of axial limitation and circumferential anti-rotation. This structure allows the device to resist disturbances caused by physiological activities after implantation in the cranium, preventing components from loosening or breaking, and providing stable structural support for subsequent drug delivery.

[0041] Subsequently, the titanium alloy substrate 3 serves as the "control center" of the device, integrating sensing and temperature-controlled sustained-release functions to provide data support and execution assurance for intelligent drug delivery. The flexible microelectrode array and gold nanowire-modified ECoG sensor embedded in the substrate can collect intracranial cortical electrophysiological signals in real time and simultaneously monitor the physiological state of the lesion area. The matching electrode point temperature-sensitive sustained-release unit uses chitosan / polyN-isopropylacrylamide hydrogel as its core, combined with a microfluidic cooling system consisting of a serpentine microchannel and a Peltier cooling plate. It can precisely match the drug release rate through temperature regulation. When abnormal lesion signals are detected, the temperature control system can dynamically adjust the working state of the sustained-release unit to achieve a linkage response of "signal monitoring-dose adjustment".

[0042] Finally, the titanium alloy substrate 3 and the diversion valve 4 are integrated into a single unit. The titanium alloy substrate is embedded in the top groove of the diversion valve to form a gapless seal, which can prevent cerebrospinal fluid from corroding the valve body. The main body of the diversion valve is made of PEEK or titanium alloy, and the internal channels use medical-grade silicone, thermoplastic polyurethane, etc. as diaphragms to achieve drug isolation. The channel surface is heparinized to reduce the risk of thrombosis. Its core advantage lies in the intelligent controlled-release algorithm, which can dynamically adjust the flow rate and release sequence of each channel based on the real-time biological signals transmitted by the titanium alloy substrate. The flow rate error is controlled within ±1%, which fundamentally avoids the toxic side effects caused by local drug overload, and supports the simultaneous local controlled release of multiple drugs.

[0043] Four sets of drug delivery tubes 402, distributed circumferentially at the bottom of the shunt valve, provide a "precise channel" for drugs to directly reach the target area. These delivery tubes employ a three-layer composite structure to optimize performance: an inner hydrophilic polyurethane coating reduces drug flow resistance and residue; a middle metal braided mesh enhances bending resistance to adapt to complex intracranial anatomy; and an outer tantalum-containing material enhances imaging contrast and facilitates postoperative localization. The multi-stage drug release head at the end of the delivery tubes allows for microliter-level flow control. Combined with the conical self-sealing dynamic coupling design with the shunt valve, this enables precise drug delivery to millimeter-level target areas deep within the brain. The four channels can each correspond to different lesion regions, achieving independent, time-controlled drug delivery to multiple targets.

[0044] All electrical components mentioned in this article are connected to an external main controller and 220V AC mains power, and the main controller can be a conventional known device such as a computer for control.

[0045] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A skull drug injection interface for deep brain tissue sustained release administration, comprising a titanium alloy base (3) and a liquid inlet (2) arranged on one side of the titanium alloy base (3), characterized in that: The liquid inlet (2) is fixedly connected with an outer ring body (201) on the side close to the titanium alloy base (3), and the outer ring body (201) is fixedly attached to the titanium alloy base (3); the outer ring body (201) is fixedly connected with a clamping ring (203) on the side close to the titanium alloy base (3); the titanium alloy base (3) is provided with a clamping groove (301) on the side close to the clamping ring (203), and the clamping ring (203) is arranged in the clamping groove (301) and fixedly attached thereto; the titanium alloy base (3) is fixedly attached with an inner ring body (202) on the inner wall side away from the outer ring body (201), and the inner ring body (202) is fixedly connected with the liquid inlet (2) on the side close to the liquid inlet (2); the titanium alloy base (3) is provided with a shunt valve (4) on the side away from the liquid inlet (2), and the titanium alloy base (3) is arranged in the shunt valve (4) and fixedly connected thereto on the side close to the shunt valve (4).

2. The skull drug infusion interface for slow-release drug delivery to deep brain tissue according to claim 1, wherein: The liquid inlet (2) is provided with a biological gasket (1) on the side away from the outer ring body (201), and the biological gasket (1) is fixedly connected with a gasket ring (101) on the side close to the liquid inlet (2), and the gasket ring (101) is arranged in the liquid inlet (2) and fixedly attached thereto.

3. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 1, wherein: The shunt valve (4) is fixedly provided with a liquid inlet valve (401) on the side close to the titanium alloy base (3), and the liquid inlet valve (401) extends to the inside of the titanium alloy base (3) on the side close to the titanium alloy base (3) and is fixedly connected thereto.

4. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 1, wherein: Four groups of drug delivery tubes (402) are inserted and installed on the side away from the titanium alloy base (3) along the circumference of the shunt valve (4), which can accurately deliver drugs to specific target areas in the deep brain and achieve precise treatment in different areas of the brain.

5. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 4, wherein: The drug delivery tube (402) has ultra-fine inner diameter and ultra-high bending fatigue life, adopts a three-layer composite structure, the inner layer is a hydrophilic polyurethane coating to reduce flow resistance, the middle layer is a medical-grade stainless steel or nickel-titanium alloy woven mesh to resist bending, and the outer layer is a tantalum powder-containing silicone or PEEK to enhance the development of the drug delivery tube (402). The end is designed as a multi-stage drug release head, the flow control precision needs to reach the order of microliters per minute, and the drug delivery tube (402) is dynamically coupled with the shunt valve (4) through a conical self-sealing interface to achieve millimeter-level targeted drug delivery in brain tissue and multi-channel time sequence control.

6. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 1, wherein: The main body of the shunt valve (4) is made of PEEK or titanium alloy material, and one or more of medical silicone, thermoplastic polyurethane, and expanded polytetrafluoroethylene is used as the diaphragm material in the channel, and the entire channel surface is treated with heparin. The shunt valve (4) adjusts the flow rate and release timing of each channel according to real-time biological signals as needed, and the control algorithm can control the flow error within ±1 to avoid local drug overload.

7. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 2, wherein: The biological gasket (1) is made of one or more of titanium / silicone implant outer shell, titanium / PEEK skull plate, and collagen matrix, and the interface between the biological gasket (1) and the titanium alloy base (3) is coated with light-cured bone cement or bioactive light-cured composite material, and the shear strength after curing is greater than 18MPa.

8. The skull drug infusion interface for slow-release drug delivery to deep brain tissue of claim 1, wherein: The titanium alloy base (3) internally includes a flexible micro electrode array and a scalp electroencephalogram sensor modified with gold nanowires, and an electrode point temperature sensitive slow release unit in the titanium alloy base (3) is composed of a microfluidic cooling layer of chitosan / poly N-isopropyl acrylamide hydrogel, and a built-in serpentine microchannel and a Peltier refrigeration sheet.

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