Drug-loaded totally-implanted cochlear microphone and method of making same

Abstract

The application discloses a drug-loaded totally-implanted cochlear microphone and a manufacturing method thereof, and comprises an active sound receiving part, a titanium alloy shell and a drug-loaded component, a plurality of microgrooves or microholes are formed in the titanium alloy shell, and the drug-loaded component is arranged in the microgrooves / microholes; the active sound receiving part comprises a PCBA board and a sound sensor, the sound sensor receives external vibration and converts the external vibration into an electric signal, and the PCBA board can receive the electric signal; a loop response electrode wire is arranged in the microgrooves or the microholes, and two ends of the loop response electrode wire are electrically connected with the PCBA board; when the PCBA board receives the electric signal and a preset electric signal, the PCBA board controls the loop response electrode wire to send a stimulation signal to stimulate the drug-loaded component to release active drugs; according to the application, the drug-loaded component is accommodated in the microgrooves / microholes, the loop response electrode wire is connected with the PCBA board, when the inflammation around the microphone changes and causes sound receiving change, the size of the pores of the drug-loaded polymer matrix is stimulated, so that the active drugs are dissolved to adapt to the treatment requirement of the current inflammation.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, and specifically relates to a drug-loaded fully implantable cochlear implant microphone and its manufacturing method. Background Technology

[0002] Cochlear implants remain the most effective treatment for restoring hearing function in patients with severe to profound sensorineural hearing loss. A traditional cochlear implant system consists of an external sound processor, an internal receiver / stimulator, and a transcutaneous wireless signal transmission link. The microphone of the external sound processor receives the sound signal, which is then digitized, processed, and encoded by the processor. The encoded sound signal is then transmitted by the transmission coil to the internal receiver coil via the transcutaneous wireless transmission link. The implanted stimulation chip decodes the signal and converts it into a corresponding electrical signal, which then sends electrical impulses to the auditory nerve, stimulating the nerve and transmitting nerve impulses to the auditory center of the brain, allowing the patient to hear. However, the visibility and prominence of the external processor can lead to negative social perceptions of hearing impairment. It is also unusable during certain activities (such as sleeping, bathing, and swimming) and is easily damaged by accidental impacts. Furthermore, the microphone of a traditional cochlear implant is located outside the ear or at the entrance of the external auditory canal, preventing users from utilizing the passive gain of the external auditory canal at speech-related frequencies and from fully benefiting from the shadowing effect of the auricle, which can attenuate sounds from behind and potentially provide directional cues. Furthermore, the external sound processor restricts the use of standard head-mounted devices, such as headphones and helmets, which not only inconveniences patients but also serves as a reminder of their hearing impairment.

[0003] Fully Implantable Cochlear Implant (TICI) technology eliminates external hardware by implanting the microphone, DSP, and battery entirely within the body, providing a more discreet, durable, and all-weather hearing solution, which will increase the acceptance rate of cochlear implantation. In the design process of fully implantable cochlear implants, the implantable microphone (sensor) is one of the key challenges that urgently needs to be overcome. The implantable microphone must meet the following basic requirements: 1) The implantable microphone must have sufficient sensitivity, dynamic range, and bandwidth to achieve performance similar to external microphones. 2) The microphone, which is implanted long-term, must not cause adverse reactions in biological tissues and can withstand repeated micro-movements and external impacts that may occur over a lifetime, potentially lasting decades. The outer shell must be impermeable to surrounding bodily fluids. 3) Low-power design to minimize device size and maximize internal battery life. 4) Appropriate size for easy surgical implantation. In addition, fully implantable cochlear implants also face clinical challenges, including surgical complexity and physiological noise interference. Surgery for implantable devices is generally more complex than that for traditional cochlear implants, requiring precise implantation location and delicate surgical techniques. Noise produced during chewing, swallowing, or speaking can affect speech clarity.

[0004] Based on the aforementioned requirements, implantable microphones are generally constructed from a titanium alloy shell and an active sound-receiving component (including a diaphragm, signal sensor, PCBA, feedthrough, and wiring). The titanium alloy shell ensures that the active component is isolated from human tissue, preventing issues such as tissue compression and short circuits caused by tissue fluid. However, the titanium alloy shell is a hard metal material, and although it has relatively good biocompatibility, it can still cause tissue rejection, leading to inflammation, ossification, and fibrosis. When this inflamed and fibrotic tissue encapsulates the microphone, it inevitably causes poor sound penetration and unstable sound quality. Therefore, post-implantation anti-inflammatory treatment also requires attention and resolution.

[0005] Current methods for loading and releasing drugs on titanium alloys primarily involve surface modification followed by the attachment of a drug coating. However, the titanium alloy shell of a fully implantable cochlear implant also requires surface treatment to enhance biocompatibility and silicone adhesion. Modification may damage this surface treatment layer, affecting its original performance. Furthermore, the modified titanium alloy shell surface is more prone to cracking, leading to leakage. On the other hand, the aforementioned techniques struggle to dynamically adjust the drug release rate according to changes in the patient's condition, potentially resulting in over- or under-drug administration. Summary of the Invention

[0006] To solve the above problems, the technical solution of the present invention is as follows: a drug-loaded fully implantable cochlear implant microphone, comprising an active sound receiving part, a titanium alloy shell and a drug-loaded component, wherein the active sound receiving part is located inside the titanium alloy shell, and the titanium alloy shell is provided with a plurality of microgrooves or microholes, and the drug-loaded component is disposed in the microgrooves or microholes;

[0007] The active sound receiving unit includes a PCBA board and a sound sensor. The sound sensor receives external vibration signals and converts them into electrical signals. The PCBA board is electrically connected to the sound sensor and can receive the electrical signals output by the sound sensor. A loop response electrode wire is provided in the microgroove or micropore. The two ends of the loop response electrode wire are electrically connected to the PCBA board. When the electrical signal received by the PCBA board differs from the preset electrical signal, the PCBA board controls the loop response electrode wire to emit a stimulation signal to stimulate the drug-carrying component to release active drugs.

[0008] Preferably, the drug-carrying component includes a drug-carrying polymer matrix, in which an active drug is disposed. After being stimulated by the stimulation signal, the drug-carrying polymer matrix can expand its own pores to allow the active drug to move out of the drug-carrying polymer matrix.

[0009] Preferably, the drug-carrying component is disposed within the microgroove, the width of the microgroove is 0-5 mm, and the depth of the microgroove is 0-0.5 mm; the cross-section of the microgroove along the thickness direction of the titanium alloy shell is one or more of a square, rectangle, arc, and polygon.

[0010] Alternatively, the drug-carrying component may be disposed within the micropores, the inner diameter of the micropores being 0–5 mm and the depth of the micropores being 0–0.5 mm; the cross-section of the micropores along the thickness direction of the titanium alloy shell may be one or more of the following: square, rectangle, arc, and polygon.

[0011] Preferably, the outer wall of the titanium alloy shell is provided with an annular groove, and the drug-carrying component is disposed in the annular groove.

[0012] Preferably, the active sound receiver further includes a pickup diaphragm and a wire. The pickup diaphragm is fixedly mounted on the titanium alloy housing and is used to collect external vibration signals and transmit them to the sound sensor. The sound sensor converts the external vibration signals into electrical signals and then transmits them to the PCBA board for amplification and noise reduction.

[0013] Preferably, the drug-loaded polymer matrix comprises 50-100 wt% of a drug-loaded polymer matrix and 0-50 wt% of a drug-loaded adjuvant; the drug-loaded polymer matrix is ​​one or more of polylactide, polyglycolic acid, glycolide-lactide copolymer, polyethylene glycol, polycaprolactone, polyacrylamide, polylactic acid, poly-4-hydroxybutyrate, and silicone rubber; the drug-loaded adjuvant is a release regulator or a pore-forming agent.

[0014] Preferably, the drug-loaded polymer matrix is ​​one of an electroresponsive polymer, a thermally responsive polymer, or a pH-responsive polymer.

[0015] Preferably, the drug-loading adjuvant is one or more of the following: hydroxypropyl methylcellulose, hyaluronic acid and its sodium salt, poloxamer, polyethylene glycol, polyether, polyvinyl alcohol, polyvinylpyrrolidone, lactose, mannitol, glucose, maltose, sorbitol, sodium lauryl sulfate, sodium chloride, potassium chloride, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, or sucrose.

[0016] A method for manufacturing a drug-loaded, fully implantable cochlear implant microphone includes the following steps:

[0017] Fabricate titanium alloy top and bottom caps with microgrooves or micropores, and perform biocompatible surface treatment accordingly.

[0018] Weigh the drug-loaded polymer matrix and drug-loaded adjuvant into a container according to the preset weight percentage, and stir to mix and degas to obtain a uniformly mixed and degassed drug-loaded polymer matrix.

[0019] The drug-loaded polymer matrix is ​​filled into the microgrooves or micropores of the titanium alloy top cover and cured to form a drug-loaded component, which is then bonded to the titanium alloy top cover.

[0020] A sound sensor and PCBA board were fabricated, assembled with feedthrough and wires, and encapsulated in a titanium alloy housing assembled from a titanium alloy top cover and a titanium alloy bottom cover. The pickup diaphragm was then installed on the titanium alloy top cover to obtain a drug-loaded fully implantable cochlear implant microphone.

[0021] The beneficial effects of this invention are as follows:

[0022] 1. The drug-loaded fully implantable cochlear implant microphone of the present invention embeds the drug-loaded component into the titanium alloy shell through microgrooves / micropores or annular grooves, so that the drug-loaded component and the titanium alloy shell are tightly bonded by physical means without the need to modify the surface of the titanium alloy shell, thus avoiding the leakage problem caused by cracks on the surface of the shell after modification; at the same time, the drug-loaded component on the titanium alloy shell is used for long-term treatment of inflammation, fibrosis and other diseases after microphone implantation, and also helps to improve the microphone's ability to pick up external sounds.

[0023] 2. The drug-loaded fully implantable cochlear implant microphone of the present invention has a loop response electrode wire set in a microgroove or micropore and connected to a PCBA board. When the inflammation or fibrosis around the microphone changes, causing a change in the microphone's sound reception effect, the PCBA board detects the change and sends a corresponding stimulation signal to stimulate the drug-loaded component to release the active drug, thereby achieving dynamic adjustment of drug delivery. In addition, the stimulation signal can stimulate the pore size of the drug-loaded polymer matrix, so that the rate of dissolution of the active drug is adapted to the current needs of inflammation or fibrosis treatment.

[0024] 3. The drug-loaded fully implantable cochlear implant microphone of the present invention uses a drug-loaded polymer matrix that employs an intelligently responsive electro-reactive polymer, a thermally responsive polymer, or a pH-responsive polymer material. That is, it can generate porosity changes under stimulation such as electricity, heat, or pH, thereby dynamically adjusting the drug release rate so that the rate at which the drug dissolves from the polymer is adapted to the current needs of inflammation or fibrosis treatment. The drug-loaded polymer matrix includes an appropriate proportion of drug-loaded polymer body and drug-loaded adjuvants. Through the interaction of the two, dynamic regulation of drug delivery can be better achieved, further meeting the treatment needs.

[0025] 4. The drug-loaded fully implantable cochlear implant microphone of the present invention further improves the treatment effect and meets the treatment needs of different users by optimizing the shape, depth and size of the microgroove or micropore.

[0026] 5. The manufacturing method of the drug-loaded fully implantable cochlear implant microphone of the present invention is relatively simple and easier to adapt to the processing technology of implantable microphones; at the same time, it does not require modification of the titanium alloy shell and will not affect the original surface treatment layer. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the structure of a drug-loaded fully implantable cochlear implant microphone according to a specific embodiment of the present invention;

[0028] Figure 2 This is a schematic diagram of the structure of a drug-loaded fully implantable cochlear implant microphone according to a specific embodiment of the present invention;

[0029] Figure 3 This is a schematic diagram of the structure of a drug-loaded fully implantable cochlear implant microphone according to a specific embodiment of the present invention;

[0030] Figure 4 This is a schematic diagram of the structure of a drug-loaded fully implantable cochlear implant microphone according to a specific embodiment of the present invention;

[0031] Figure 5 A flowchart illustrating the release of active drugs in a drug-loaded fully implanted cochlear implant microphone according to a specific embodiment of the present invention;

[0032] Figure 6A schematic diagram illustrating the change in porosity of the drug-loaded polymer matrix stimulated by the loop-response electrode wire in a specific embodiment of the present invention.

[0033] The attached diagram is labeled as follows: 1. Metal pressure ring; 2. Sound pickup diaphragm; 3. Titanium alloy top cover; 4. PCBA board; 5. Sound sensor; 6. Titanium alloy bottom cover; 7. Bone conduction sensor; 8. Feedthrough; 9. Micropore; 10. Circular micropore array; 11. Ring groove; 12. Microgroove; 13. Circular microgroove; 14. Outer wall micropore array; 15. Circular microgroove. Detailed Implementation

[0034] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0035] See Figure 1 and Figure 2 The drug-loaded fully implantable cochlear implant microphone includes an active receiver, a titanium alloy shell, and a drug-loaded component. The active receiver is located inside the titanium alloy shell, which has several microgrooves 12 or micropores 9. The drug-loaded component is disposed within the microgrooves 12 or micropores 9. The active receiver includes a PCBA board 4, a pickup diaphragm 2, and a sound sensor 5. The pickup diaphragm 2 is fixedly mounted on the titanium alloy shell and is used to collect external vibration signals and transmit them to the sound sensor 5. The sound sensor 5 converts the external vibration signals into electrical signals. The PCBA board 4 is electrically connected to the sound sensor 5 and can receive the electrical signals output by the sound sensor 5, and can amplify and reduce noise.

[0036] Both the pickup diaphragm 2 and the sound sensor 5 can be configured in multiples, and the number can be selected as needed, which will not be elaborated here. A metal pressure ring 1 can be installed on top of the pickup diaphragm 2 to better fix the pickup diaphragm 2.

[0037] See Figure 1 and Figure 2 The titanium alloy housing includes a titanium alloy top cover 3 and a titanium alloy bottom cover 6. The titanium alloy top cover 3 and the titanium alloy bottom cover 6 are welded together to form a sealed space. The PCBA board 4 is located within this sealed space, and the sound sensor 5 is located between the PCBA board 4 and the titanium alloy top cover 3. The titanium alloy housing ensures that the active components are isolated from human tissue, avoiding problems such as tissue compression of internal active components and short circuits caused by human tissue fluid.

[0038] The active receiver also includes a feedthrough 8 and a wire. The feedthrough 8 is connected to the titanium alloy housing and the wire (not shown in the figure). The signal, after being amplified and noise-reduced by the PCBA board 4, is transmitted to the stimulator of the cochlear implant (not shown in the figure) through the feedthrough 8 and the wire.

[0039] See Figure 1 and Figure 2Furthermore, a loop response electrode wire (not shown in the figure) is provided in the microgroove 12 or microhole 9, and the two ends of the loop response electrode wire are electrically connected to the PCBA board 4. When the electrical signal received by the PCBA board 4 differs from the preset electrical signal, the PCBA board 4 controls the loop response electrode wire to emit a stimulation signal to stimulate the drug-carrying component to release the active drug.

[0040] See Figure 1 and Figure 5 The drug-loaded component is embedded in the titanium alloy shell through microgrooves 12 / micropores 9 or annular grooves 11, allowing for a tight physical bond between the drug-loaded component and the titanium alloy shell. This eliminates the need for surface modification of the titanium alloy shell, avoiding leakage problems caused by surface cracks resulting from shell modification. Furthermore, by incorporating loop-response electrode wires in the microgrooves 12 or micropores 9 and connecting them to the PCBA board 4, when changes in inflammation or fibrosis around the microphone cause alterations in the microphone's sound reception, the PCBA board 4 detects these changes and emits a corresponding stimulation signal to stimulate the drug-loaded component to release the active drug, achieving dynamic drug delivery regulation. Moreover, the stimulation signal can adjust the pore size of the drug-loaded polymer matrix, thereby adapting the rate of active drug dissolution to the current needs of inflammation or fibrosis treatment.

[0041] Specifically, see Figure 5 When the inflammation or fibrosis around the microphone changes, the sound sensor 5 receives a change in sound volume / frequency. At this time, the PCBA board detects the change and sends out a corresponding stimulation signal. The stimulation signal stimulates the drug-loaded component through the loop response electrode wire. Furthermore, the stimulation signal stimulates the pore size and porosity of the drug-loaded polymer matrix of the drug-loaded component, thereby changing the rate of release of the active drug and providing feedback to adapt to the current inflammation or fibrosis problem.

[0042] See Figure 2 The drug-carrying component can be disposed within the microgroove 12. Further, the width of the microgroove 12 can be 0–5 mm, and the depth of the microgroove 12 can be 0–0.5 mm. The cross-section of the microgroove 12 along the thickness direction of the titanium alloy shell is one or more of a square, rectangle, arc, and polygon, as detailed below. Figure 2 The microgrooves 13 are circular or annular. Alternatively, the drug-carrying component can also be located within the micropores 9, with an inner diameter of 0–5 mm and a depth of 0–0.5 mm. The cross-section of the micropores 9 along the thickness direction of the titanium alloy shell is one or more of a square, rectangle, arc, or polygon shape, as detailed in [link to details]. Figure 2 The circular micropore array 10 in the middle.

[0043] See Figure 2 and Figure 3The outer wall of the titanium alloy shell is provided with an annular groove 11, and the drug-carrying component can also be disposed within the annular groove 11. Furthermore, a responsive loop electrode wire can also be disposed within the annular groove 11 and electrically connected to the PCBA board 4 to achieve dynamic adjustment of drug delivery. See also Figure 2-4 Various combinations of microgrooves 12, micropores 9, and annular grooves 11 can be provided on the titanium alloy shell. The drug-carrying component can be simultaneously disposed within the microgrooves 12, micropores 9, and annular grooves 11, or at least one arrangement or combination can be selected as needed. For example, in one specific embodiment, an outer wall micropore array 14 can be provided on the outer wall of the titanium alloy shell, and the upper surface of the titanium alloy shell is provided with micropores 9 and circular micropore arrays 10. Alternatively, in another specific embodiment, annular grooves 11 can be provided on the outer wall of the titanium alloy shell, and the upper surface of the titanium alloy shell is provided with microgrooves 12, which will not be elaborated here.

[0044] The drug-loaded component comprises 5-95 wt% active drug and 5-95 wt% drug-loaded polymer matrix, wherein the active drug component is uniformly dispersed in the drug-loaded polymer matrix.

[0045] See Figure 6 The drug-loaded polymer matrix is ​​one of the following: an electroresponsive polymer, a thermally responsive polymer, or a pH-responsive polymer. It can produce porosity changes under stimulation such as electricity, heat, or pH, thereby dynamically regulating the release rate of the active drug.

[0046] See Figure 1 Various noise sources exist within the human body. These include the sound of blood flow, the vibrations caused by the heartbeat, and the sounds produced by muscle movement. These internal noises, along with external sounds, are received by the microphone in the implanted cochlear implant, resulting in a noisy sound signal that severely impacts the patient's hearing. Therefore, a bone conduction sensor 7 can be installed on the titanium alloy base cover 6. The bone conduction sensor 7 fits snugly against the bone surrounding the ear through the titanium alloy base cover 6. As the bone vibrates due to internal noise, the bone conduction sensor 7 converts these vibrations into electrical signals, accurately collecting the internal noise signals and transmitting them to the PCBA board 4 for processing. This effectively reduces internal noise and improves the patient's hearing experience.

[0047] Drug-loaded polymer matrices are a class of materials that can spontaneously respond to external stimuli, such as smart responsive gels, smart responsive liquid crystal polymers, and smart responsive shape memory polymers.

[0048] The principle behind the porosity change of smart responsive gels is as follows: Under different external stimuli, the amount of solvent swollen inside the gel varies, resulting in different pore sizes. Therefore, when receiving external stimuli, the degree of gel swelling changes, causing the solvent inside to be extruded / absorbed, thus altering the material's porosity.

[0049] The principle behind the porosity change of intelligent responsive liquid crystal polymers is as follows: Under different external stimuli, the degree of order in the arrangement of liquid crystal molecules varies, resulting in different internal free volumes. Therefore, when receiving external stimuli, the internal arrangement of the liquid crystal polymer changes / reverses from an orderly arrangement to an irregular arrangement, causing a change in the material's porosity.

[0050] The principle behind the porosity change of intelligent shape memory polymers is as follows: Shape memory polymers all possess a two-phase structure, consisting of a stationary phase that remembers the initial shape and a reversible phase that can reversibly solidify and soften with temperature changes. The stationary phase can be a cross-linked structure, a partially crystalline structure, a glassy state of the polymer, or an entanglement of ultrapolymer chains. The reversible phase can be a partially crystalline phase that undergoes reversible changes between crystallization and melting, or a phase structure that undergoes reversible changes between a glassy and rubbery state (glass transition temperature Tg). When receiving external stimuli, the reversible phase undergoes a phase transition, causing the release of internal stress in the material and resulting in a change in the porosity of the material.

[0051] In summary, the controllable drug release mechanism of the intelligent response drug delivery component can be found in [reference needed]. Figure 6 Active drug particles are immobilized within the molecular network of a drug-loaded polymer matrix material. After the drug-loaded fully implantable cochlear implant microphone is inserted into the body, the active drug is slowly released into the tissue fluid through dissolution and diffusion. The drug release rate is controlled by the porosity of the drug-loaded polymer matrix. When a modulation signal stimulates the drug-loaded component via the loop response electrode wire, the porosity of the drug-loaded polymer matrix changes, thereby altering the rate of dissolution and diffusion of the active drug.

[0052] Furthermore, the electroresponsive polymeric material has an electroresponsive range of 0 μA to 2000 μA and a porosity range of 0.01% to 1000%; the thermally responsive polymeric material has a thermal response temperature range of 0℃ to 60℃ and a porosity range of 0.01% to 1000%; and the pH-responsive polymeric material has a pH response range of 0 to 14 and a porosity range of 0.01% to 1000%.

[0053] Specifically, the drug-loaded polymer matrix comprises 50-100% by weight of the drug-loaded polymer body and 0-50% by weight of the drug-loaded adjuvant. The drug-loaded polymer matrix includes an appropriate proportion of the drug-loaded polymer body and the drug-loaded adjuvant. Through their synergistic interaction, dynamic regulation of drug delivery is better achieved, further meeting therapeutic needs. The drug-loaded polymer body is one or more of polylactide, polyglycolic acid, glycolide-lactide copolymer, polyethylene glycol, polycaprolactone, polyacrylamide, polylactic acid (L-L), poly4-hydroxybutyrate, and silicone rubber. The drug-loaded adjuvant is a release regulator or porogen; it is one or more of hydroxypropyl methylcellulose, hyaluronic acid and its sodium salt, poloxamer, polyethylene glycol, polyether, polyvinyl alcohol, polyvinylpyrrolidone, lactose, mannitol, glucose, maltose, sorbitol, sodium lauryl sulfate, sodium chloride, potassium chloride, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, or sucrose.

[0054] The active pharmaceutical ingredient is selected from cortisone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, prednisone, prednisolone, methylprednisolone, prednisone, dexamethasone, dexamethasone acetate, dexamethasone sodium phosphate, clobetasol butyrate, betamethasone, betamethasone valerate, betamethasone dipropionate, beclomethasone propionate, clobetasol propionate, flumethasone, halometasone, flumethasone, and flumethasone tervalerate. One or a combination of mometasone furoate, fluocinolone acetonide, fluocinolone acetonide, triamcinolone acetonide, triamcinolone acetonide, halcinonide, ancinonide, desosonide, budesonide, fluticasone, defucoid, cytarabine, cytarabine hydrochloride, nicotinamide adenine dinucleotide, and one or a combination of insulin-like growth factor, hepatocyte growth factor, brain-derived neurotrophic factor, laminin, and peptide inhibitors.

[0055] In summary, the drug-loaded fully implantable cochlear implant microphone of the present invention embeds the drug-loaded component into the titanium alloy shell through microgrooves 12 / micropores 9 or annular grooves 11, so that the drug-loaded component and the titanium alloy shell are physically tightly bonded, without the need for surface modification of the titanium alloy shell, thus avoiding leakage problems caused by surface cracks after shell modification. At the same time, the drug-loaded component on the titanium alloy shell is used for long-term treatment of inflammation, fibrosis and other diseases after microphone implantation, which also helps to improve the microphone's sound pickup effect. In addition, a circuit response electrode wire is set and connected to the PCBA board 4. When the inflammation or fibrosis around the microphone changes, causing changes in the microphone's sound pickup effect, the PCBA board 4 detects the change and sends a corresponding stimulation signal to stimulate the drug-loaded component to release active drugs, thereby realizing dynamic adjustment of drug delivery. In addition, the stimulation signal can stimulate the pore size of the drug-loaded polymer matrix, so that the dissolution rate of active drugs is adapted to the current needs of inflammation or fibrosis treatment.

[0056] The method for fabricating a drug-loaded, fully implantable cochlear implant microphone includes the following steps:

[0057] S1: Fabricate a titanium alloy top cover 3 and a titanium alloy bottom cover 6 with microgrooves 12 or micropores 9, and perform biocompatible surface treatment accordingly.

[0058] S2: Weigh the drug-loaded polymer matrix and drug-loaded adjuvant into a container according to the preset weight percentage, and stir to mix and degas to obtain a uniformly mixed and degassed drug-loaded polymer matrix.

[0059] S3: Fill the microgrooves 12 or micropores 9 of the titanium alloy top cover 3 with the drug-loaded polymer matrix and cure it to form a drug-loaded component, so that the drug-loaded component is combined with the titanium alloy top cover 3.

[0060] Furthermore, when the outer wall of the titanium alloy shell is provided with an annular groove 11, the drug-carrying component can also be provided in the annular groove 11. The drug-carrying polymer matrix is ​​filled into the annular groove 11 in the same way as described above and cured to form a drug-carrying component, so that the drug-carrying component is combined with the side of the titanium alloy shell. This will not be described in detail here.

[0061] S4: Fabricate the sound sensor 5 and PCBA board 4, assemble them with the feedthrough 8 and wires, and encapsulate them in a titanium alloy housing assembled from a titanium alloy top cover 3 and a titanium alloy bottom cover 6. Install the pickup diaphragm 2 onto the titanium alloy top cover 3 to obtain a drug-loaded fully implantable cochlear implant microphone. Alternatively, when a metal retaining ring 1 is included, it can be installed on the pickup diaphragm 2 to fix the diaphragm.

[0062] The method for manufacturing the drug-loaded fully implantable cochlear implant microphone of this application is relatively simple and easier to adapt to implantable microphone processing technology. Furthermore, it requires no modification to the titanium alloy shell and does not affect the original surface treatment layer.

[0063] Finally, it should be noted that the above preferred 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 through the above preferred embodiments, those skilled in the art should understand that various changes can be made to it in form and detail without departing from the scope defined by the claims of the present invention.

Claims

1. A drug-loaded, fully implantable cochlear implant microphone, characterized in that, It includes an active sound receiver, a titanium alloy housing, and a drug-carrying component. The active sound receiver is located inside the titanium alloy housing. The titanium alloy housing has several microgrooves (12) or micropores (9). The drug-carrying component is disposed in the microgrooves (12) or micropores (9). The active sound receiving unit includes a PCBA board (4) and a sound sensor (5). The sound sensor (5) receives external vibration signals and converts them into electrical signals. The PCBA board (4) is electrically connected to the sound sensor (5) and can receive the electrical signals output by the sound sensor (5). The sound volume and / or sound frequency of the sound sensor (5) are analyzed according to the electrical signals. A loop response electrode wire is provided in the microgroove (12) or microhole (9). The two ends of the loop response electrode wire are electrically connected to the PCBA board (4). When the sound volume and / or sound frequency changes compared to the preset sound volume and / or sound frequency, the PCBA board (4) determines that inflammation or fibrosis has occurred around the microphone. In response to the determination result, the PCBA board (4) controls the loop response electrode wire to emit a stimulation signal to stimulate the drug-loaded component to release active drugs. The drug-carrying component includes a drug-carrying polymer matrix, in which an active drug is disposed. When stimulated by the stimulation signal, the drug-carrying polymer matrix can expand its pores to allow the active drug to move out of the drug-carrying polymer matrix. The drug-carrying polymer matrix is ​​one of an electroresponsive polymer, a thermally responsive polymer, or a pH-responsive polymer.

2. The drug-loaded fully implantable cochlear implant microphone according to claim 1, characterized in that, The drug-carrying component is disposed in the microgroove (12), the width of the microgroove (12) is 0~5 mm, and the depth of the microgroove (12) is 0~0.5 mm; the cross section of the microgroove (12) along the thickness direction of the titanium alloy shell is one or more of the following: square, rectangle, arc, polygon; Alternatively, the drug-carrying component is disposed within the micropore (9), the inner diameter of the micropore (9) is 0~5 mm, and the depth of the micropore (9) is 0~0.5 mm; the cross section of the micropore (9) along the thickness direction of the titanium alloy shell is one or more of square, rectangle, arc, and polygon.

3. The drug-loaded fully implantable cochlear implant microphone according to claim 1, characterized in that, The outer wall of the titanium alloy shell is provided with an annular groove (11), and the drug-carrying component is disposed in the annular groove (11).

4. The drug-loaded fully implantable cochlear implant microphone according to claim 1, characterized in that, The active sound receiver also includes a pickup diaphragm (2) and a wire. The pickup diaphragm (2) is fixedly installed on the titanium alloy housing and is used to transmit external vibration signals to the sound sensor (5). The sound sensor (5) converts the external vibration signals into electrical signals and then transmits them to the PCBA board (4) for amplification and noise reduction.

5. The drug-loaded fully implantable cochlear implant microphone according to claim 1, characterized in that, The drug-loaded polymer matrix comprises 50-100 wt% of a drug-loaded polymer matrix and 0-50 wt% of a drug-loaded adjuvant; the drug-loaded polymer matrix is ​​one or more of polylactide, polyglycolic acid, glycolide-lactide copolymer, polyethylene glycol, polycaprolactone, polyacrylamide, polylactic acid, poly-4-hydroxybutyrate, and silicone rubber; the drug-loaded adjuvant is a release regulator or a pore-forming agent.

6. The drug-loaded fully implantable cochlear implant microphone according to claim 5, characterized in that, The drug-loading adjuvant is one or more of the following: hydroxypropyl methylcellulose, hyaluronic acid and its sodium salt, poloxamer, polyethylene glycol, polyether, polyvinyl alcohol, polyvinylpyrrolidone, lactose, mannitol, glucose, maltose, sorbitol, sodium lauryl sulfate, sodium chloride, potassium chloride, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, or sucrose.

7. The method for manufacturing the drug-loaded fully implantable cochlear implant microphone according to any one of claims 1-6, characterized in that, Includes the following steps: A titanium alloy top cover (3) and a titanium alloy bottom cover (6) with microgrooves (12) or micropores (9) are fabricated and subjected to biocompatible surface treatment. Weigh the drug-loaded polymer matrix and drug-loaded adjuvant into a container according to the preset weight percentage, and stir to mix and degas to obtain a uniformly mixed and degassed drug-loaded polymer matrix. The drug-loaded polymer matrix is ​​filled into the microgroove (12) or micropore (9) of the titanium alloy top cover (3) and cured to form a drug-loaded component, so that the drug-loaded component is combined with the titanium alloy top cover (3). A sound sensor (5) and a PCBA board (4) are fabricated and assembled with a feedthrough (8) and wires. They are then encapsulated in a titanium alloy housing assembled from a titanium alloy top cover (3) and a titanium alloy bottom cover (6). A pickup diaphragm (2) is installed on the titanium alloy top cover (3) to obtain a drug-loaded fully implantable cochlear implant microphone.

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