Corneal contact lens and drug sustained release method

Abstract

The present application provides a corneal contact lens, which is a multi-layer structure with an arc-shaped curved surface, and the curvature matches the corneal curvature; it includes a micro-control circuit layer, a drug release layer and an active oxygen detection layer; the micro-control circuit layer includes a microprocessor and a heating circuit, and the microprocessor controls the heating circuit to heat to a predetermined temperature or turn it off; the drug release layer is a thermal phase change material layer mixed with drug molecules and is bonded to the micro-control circuit layer, and releases the drug molecules when heated by the heating circuit; gaps are distributed on the active oxygen detection layer, and it is bonded to the drug release layer and electrically connected to the micro-control circuit layer; when the active oxygen detection layer detects active oxygen, it is sensed by the microprocessor, and the microprocessor controls the release rate of the drug molecules according to the sensed result and by controlling the heating circuit to heat to a predetermined temperature or turning off the heating circuit, and the drug molecules act on the cornea through multiple gaps; the contact lens of the present application achieves precise treatment of eye inflammation through the synergistic effect of the multi-layer structure, is easy to use and has significant effects.

Description

Technical Field

[0001] The present application relates to the field of intelligent medical technology, and in particular to a corneal contact lens and drug sustained-release technology. Background Art

[0002] Dry eye syndrome, also known as sicca, is a common ophthalmological disease, the main characteristics of which are dry eyes, discomfort, sometimes accompanied by pain and blurred vision. The medical name of dry eye syndrome is Dry eye syndrome, abbreviated as DES. Dry eye syndrome is an ocular surface disease caused by multiple factors, and its symptoms include but are not limited to dry eyes, foreign body sensation, burning sensation, fatigue, and visual fluctuations. These symptoms may have a negative impact on the patient's quality of life, such as affecting daily life activities such as reading, using electronic devices, and driving. In some severe cases, dry eye syndrome may even lead to visual impairment. The causes of dry eye syndrome are varied, including insufficient tear secretion, poor tear quality, and abnormal function of intrinsic tissue cells on the ocular surface.

[0003] Among the various mechanisms of disease occurrence and development that cause dry eye syndrome, reactive oxygen species (ROS) are classic products of oxidative stress imbalance. Trace amounts of ROS formation can serve as second messengers in cell activity reactions, while the production and accumulation of a considerable amount of ROS will lead to the decompensation of the inherent corneal epithelial cells in the ocular surface microenvironment, causing potential corneal epithelial defects; excessive ROS levels will cause the activation of local inflammatory cascades, and the inflammatory factor waterfall will cause insufficient or poor tear secretion. The imbalance of tear composition and the sharp decrease in secretion will make the ocular surface tissue more directly exposed to dry air. The production and accumulation of ROS is the starting link for the activation of the inflammatory pathway in the ocular surface microenvironment, and it can damage corneal epithelial cells, causing the corneal epithelial cells to decompensate during the oxidation process, and even lose cell activity or even die. Therefore, the rapid increase in ROS levels indicates the activation of the NLRP3 inflammasome, a key pathway of ocular surface microenvironment inflammation, and indicates the risk of corneal epithelial cell death.

[0004] The diagnosis of dry eye syndrome mainly relies on medical history and eye examination. Doctors may perform some specific examinations, such as tear secretion test and ocular surface staining test, to help determine the type and severity of dry eye syndrome. There are various treatments for dry eye syndrome, including the use of artificial tears, ocular anti-inflammatory drugs, drugs that regulate tear secretion, etc. In some cases, abnormal proliferation of ocular surface tissue, epithelial keratinization, and chronic inflammatory tissue hyperplasia caused by severe dry eye can also be improved by surgery. In general, ocular surface drug release is the first choice for dry eye and is the mainstream clinical intervention strategy. In the current market, ocular surface drug release is mainly achieved in the form of eye drops and ointments. However, these methods often lead to a rapid increase in drug concentration in the ocular surface microenvironment in a short period of time. These direct drug administration treatments often have transient loss and short action time, resulting in a rapid increase in drug concentration in the ocular surface microenvironment in a short period of time. The intervention time point misses the peak of disease progression, and local severe lesions on the ocular surface cannot receive targeted treatment. There are obvious shortcomings. Excessive drug concentration may irritate ocular surface biological tissues (such as corneal epithelium, conjunctival epithelium, conjunctival goblet cells and lacrimal glands) and even cause drug toxicity damage. Summary of the invention

[0005] The present application aims to provide a corneal contact lens, comprising: the contact lens is a multi-layer structure with an arc-shaped surface, the curvature of the arc-shaped surface matches the curvature of the cornea; the multi-layer structure comprises: a micro-control circuit layer, a drug release layer and a ROS detection layer; the micro-control circuit layer comprises a microprocessor and a heating circuit, the microprocessor controls the heating circuit to heat to a predetermined temperature or to be turned off; the drug release layer is a thermal phase change material layer mixed with drug molecules and is bonded to the micro-control circuit layer, and releases drug molecules when heated by the heating circuit; gaps are distributed on the ROS detection layer, and are bonded to the drug release layer and electrically connected to the micro-control circuit layer; when the ROS detection layer detects ROS, it is sensed by the microprocessor, and the microprocessor controls the release rate of the drug molecules according to the sensed result and by controlling the heating circuit to heat to a predetermined temperature or turning off the heating circuit, and the drug molecules act on the cornea through multiple gaps.

[0006] Optionally, the ROS detection layer is an electrochemical biosensor coated with ROS biorecognition molecules; when the ROS biorecognition molecules bind to the ROS, the electrochemical biosensor produces an electrochemical reaction and converts it into an electrical signal that can be measured by the microprocessor, and the microprocessor calculates the existence and concentration information of the ROS.

[0007] Optionally, the electrochemical biosensor comprises: a substrate with distributed gaps, an electrode attached to the substrate, and a ROS biorecognition molecule coated on the electrode, and the electrochemical reaction comprises: charge transfer and / or current and / or potential change.

[0008] Optionally, the substrate is in a disc-shaped spiral structure and is attached to the drug-releasing layer, and spiral coil-shaped gaps are distributed on the disc-shaped spiral structure, and the drug molecules act on the cornea through the spiral coil-shaped gaps.

[0009] Optionally, when the microprocessor detects the presence of the ROS, it starts the heating circuit and sets the heating temperature according to the ROS concentration.

[0010] Optionally, the micro-control circuit layer is covered with a packaging film, and the packaging film and the substrate are made of a material with hydrophilic and oxygen-permeable properties.

[0011] Optionally, the drug molecules include inhibitor MCC950 and epidermal growth factor EGF, which correspond to the specific inhibitor of NLRP3 inflammasome, a key site of the inflammatory pathway, and epidermal growth factor EGF, which is beneficial to the repair of corneal epithelial cell damage. The inhibitor MCC950 and epidermal growth factor EGF are mixed with a thermal phase change material to form a thermal phase change material layer and are closely attached to the heating circuit. The thermal phase change material layer undergoes a phase change when heated by the heating circuit, and the speed of the phase change is controlled by controlling the heating temperature to adjust the release rate of the drug molecules.

[0012] Optionally, the micro-control circuit layer also includes a micro-power source, and is electrically connected to the heating circuit and the ROS detection layer respectively through the microprocessor. When the microprocessor calculates that the ROS concentration change rate is less than a preset value, the microprocessor continuously releases current for a predetermined period of time to the ROS detection layer to clear the reactants.

[0013] Optionally, the material having hydrophilic and oxygen-permeable properties is a hydrogel.

[0014] According to another aspect of the present application, the present application also provides a method for sustained release of ocular drugs for a corneal contact lens as described above, the method comprising: using a ROS detection layer to detect ROS, and generating an electrical signal to a microprocessor; the microprocessor calculates the existence and concentration information of the ROS based on the received electrical signal; when the microprocessor detects the presence of the ROS, the microprocessor starts a heating circuit to heat the drug release layer to a predetermined temperature or turns off the heating circuit to control the release rate of the drug molecules based on the concentration information, and the released drug molecules act on the cornea through the gaps in the ROS detection layer, and when the microprocessor calculates that the rate of change of the ROS concentration is less than a preset value, the microprocessor continuously releases an electric current for a predetermined period of time to the ROS detection layer.

[0015] When the ROS biorecognition molecule binds to the ROS on the contact lens, the electrochemical biosensor will immediately undergo an electrochemical reaction to generate a measurable electrical signal. These electrical signals are captured and interpreted by the microprocessor to accurately calculate the presence or absence of ROS and its concentration information.

[0016] In the design of the electrochemical biosensor, we specially selected a substrate material with excellent conductivity and evenly distributed tiny gaps on its surface. The electrodes are closely attached to these gaps, and the ROS biorecognition molecules are coated on the electrode surface to ensure efficient charge transfer and current changes. This design not only improves the sensitivity and accuracy of the sensor, but also ensures a rapid response to the detection results.

[0017] When the microprocessor detects the presence of ROS, it automatically adjusts the temperature of the heating circuit according to the ROS concentration. In this way, we can achieve precise control of the drug release rate, ensuring that the drug can act on the cornea at the predetermined rate and dose.

[0018] In addition, we have specially designed a drug release layer that contains a variety of drug molecules, such as the inhibitor MCC950 and epidermal growth factor EGF. These drug molecules are mixed with thermal phase change materials. When the heating circuit is activated, the thermal phase change material undergoes a phase change, thereby controlling the release rate of the drug molecules. In this way, we can flexibly adjust the drug release rate and dosage according to the health status of the cornea and treatment needs.

[0019] In order to ensure the comfort and safety of corneal contact lenses, we use hydrophilic and oxygen-permeable hydrogel materials to make encapsulation films and substrates. These materials not only have good biocompatibility, but can also effectively prevent the loss of water and oxygen, thereby keeping the cornea moist and breathing smooth.

[0020] Finally, we also designed an intelligent maintenance mechanism. When the microprocessor detects that the rate of change of ROS concentration is lower than the preset value, it will automatically release current to the ROS detection layer for a predetermined period of time to remove possible accumulated reactants and restore the detection performance of the sensor. This intelligent maintenance mechanism ensures the long-term stability and reliability of the corneal contact lens. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 A schematic diagram of the structural disassembly of a corneal contact lens provided in an embodiment of the present application;

[0022] Figure 2 A schematic diagram of the drug action process provided in the embodiments of the present application;

[0023] Figure 3A schematic diagram of the overall structure of a corneal contact lens provided in an embodiment of the present application;

[0024] Figure 4 Schematic diagram of the principle of detecting ROS by the electrochemical biosensor provided in the embodiments of the present application.

[0025] Explanation of the reference numerals: 1- packaging film; 2- micro-control circuit layer; 3- drug release layer; 4- ROS detection layer; 21- microprocessor; 22 micro power supply. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0027] like Figures 1 to 4 As shown, the present application provides a corneal contact lens, comprising: the contact lens is a multi-layer structure with an arc-shaped surface, and the curvature of the arc-shaped surface matches the curvature of the cornea; the multi-layer structure comprises: a micro-control circuit layer 2, a drug release layer 3 and a ROS detection layer 4; the micro-control circuit layer 2 comprises a microprocessor and a heating circuit, and the microprocessor controls the heating circuit to heat to a predetermined temperature or turn off; the drug release layer 3 is a thermal phase change material layer mixed with drug molecules and is bonded to the micro-control circuit layer 2, and releases drug molecules when heated by the heating circuit; gaps are distributed on the ROS detection layer 4, and are bonded to the drug release layer 3 and electrically connected to the micro-control circuit layer 2; when the ROS detection layer 4 detects ROS, it is sensed by the microprocessor, and the microprocessor controls the release rate of the drug molecules according to the sensed result and by controlling the heating circuit to heat to a predetermined temperature or turning off the heating circuit, and the drug molecules act on the cornea through multiple gaps. The applicant has found that the degree of ROS accumulation concentration is directly positively correlated with the inflammatory cascade reaction. Therefore, the ROS concentration is used as the basis for determining the severity of dry eye inflammation in this application. ROS is formed by partial reduction of oxygen, the most abundant of which are hydrogen peroxide (H2O2), hypochlorous acid or hypochlorite. , superoxide anion , hydroxyl radical (OH · ) and singlet oxygen ( 1O2). ROS are byproducts of various redox reactions in different cellular compartments such as mitochondria, cytoplasm, endoplasmic reticulum and peroxisomes. Therefore, elevated ROS levels in these organelles are considered to be endogenous stimuli for subcellular targeted delivery of payloads. In general, partial reduction of oxygen forms highly reactive superoxide anions , which is a primary ROS species and a precursor of different secondary ROS species. Similarly, NADPH oxidase in phagocytes secretes and spontaneously disproportionate to form H2O2, thus producing a "respiratory burst". This disproportionation reaction is extremely fast, with a rate constant of , superoxide dismutase (SOD) can increase its rate constant by 10 4 times, reaching . By NO· and Peroxynitrite This is the only reaction that meets this kinetic requirement. .and Different from other ROS, H2O2 is the most stable ROS and can diffuse across the cell membrane. Low, but it will be partially reduced under metal catalysis to generate the most reactive ROS: OH · . In addition, myeloperoxidase (MPO) can catalyze the reaction of H2O2 with chlorine to produce HOCl. H2O2 is also reduced to water by cellular peroxidases, such as catalase (Cat), glutathione peroxidase (GPX), and peroxidoreductase (PRDX). Similarly, peroxisomes are also rich in H2O2-generating enzymes, such as D-amino acid oxidase and acetyl-Co-A oxidase, which lead to subsequent peroxidation reactions and β-oxidation of fatty acids. However, when the level of ROS generation exceeds physiological requirements, this situation will cause "redox stress", leading to oxidative damage to biological macromolecules such as DNA, lipids and proteins. The present application uses an electrochemical biosensor to detect the level of ROS concentration and then determine the condition of ocular inflammation, such as Figure 4 As shown, as an alternative embodiment, an electrochemical biosensor (such as Figure 4 ) is used for superoxide quantification. Specifically, when a threshold ROS concentration is detected: The rate of spontaneous disproportionation to generate H2O2 is greater than That is, when the ROS level exceeds the warning value, the microprocessor controls the heating circuit to heat to a predetermined temperature. Specifically, a correspondence between the ROS concentration threshold and the temperature is preset, and the microprocessor starts the heating circuit according to the correspondence. Figure 4As shown in the figure, this electrochemical biosensor consists of alternating layers of cytochrome c and polyaniline (sulfonic acid) on a gold wire electrode, and is specifically designed for the quantitative detection of superoxide. Specifically, the sensor takes advantage of the unique properties of cytochrome c and polyaniline (sulfonic acid), and through their alternating layer structure, it achieves highly sensitive and selective detection of superoxide. Cytochrome c, as a biomolecule, can effectively react with superoxide, while polyaniline (sulfonic acid), as a conductive polymer, can convert the reaction signal into an electrical signal, thereby achieving quantitative analysis of superoxide. The design of this sensor not only improves the sensitivity and accuracy of detection, but also has good stability and repeatability, providing an efficient and reliable method for the quantitative detection of superoxide.

[0028] In the present application, the micro-control circuit layer 2 of the corneal contact lens also has a wireless communication function, which can exchange data with external devices such as smart phones or dedicated monitors. Through this wireless communication function, the user can monitor the health of the eye in real time and adjust the heating temperature of the drug release layer 3 according to the feedback, thereby achieving personalized treatment.

[0029] In addition, the corneal contact lens of the present application also has a self-diagnosis function. The algorithm built into the microprocessor can automatically adjust the drug release strategy according to the feedback data of the ROS detection layer 4. For example, when it is detected that the ROS concentration continues to increase, the microprocessor will increase the frequency of drug release to alleviate the inflammatory response; conversely, when the ROS concentration decreases to a normal level, the microprocessor will reduce drug release to avoid overtreatment.

[0030] In order to further improve the comfort and safety of corneal contact lenses, the drug release layer 3 is made of biocompatible materials to ensure that the drug molecules will not cause irritation or damage to the cornea during the release process. At the same time, the thickness and drug concentration of the drug release layer 3 can be customized according to individual differences to meet the needs of different users.

[0031] During the manufacturing process, the corneal contact lenses of the present application use advanced 3D printing technology to ensure that the size and shape of each pair of contact lenses perfectly match the user's corneal curvature. In addition, 3D printing technology also allows tiny sensors and circuits to be embedded in the contact lenses, making the entire structure both thin and powerful.

[0032] In order to ensure the long-term stability and reliability of the corneal contact lens, the microprocessor and heating circuit in the micro-control circuit layer 2 are designed with low power consumption to ensure a longer battery life. At the same time, the contact lens is also equipped with an energy collection device, such as a micro solar cell or a kinetic energy converter, to use environmental energy to power the contact lens, reducing the frequency of battery replacement by users.

[0033] The corneal contact lens design provided in the present application has a curved surface that is highly matched to the natural curvature of the cornea, thereby ensuring the comfort and adaptability of the wearer. The contact lens adopts a multi-layer structure design, which not only meets the needs of visual correction, but also innovatively combines microelectronic technology with ocular drug delivery functions. This multi-layer structure mainly includes a micro-control circuit layer 2, a drug release layer 3, and a ROS detection layer 4. The micro-control circuit layer 2 serves as a core control unit and includes a microprocessor 21 and a heating circuit ( Figure 2 The heating coil shown in the figure is responsible for the functional management of the entire contact lens. The microprocessor is responsible for logical judgment and instruction output, and realizes precise regulation of the contact lens temperature by controlling the heating circuit. The drug release layer 3 uses a thermal phase change material containing drug molecules and is tightly integrated with the micro-control circuit layer 2. When the heating circuit is working, the temperature of the contact lens rises, and the drug release layer 3 responds to the heating and releases the drug molecules, realizing precise control of drug release and improving the effectiveness and safety of treatment. The ROS detection layer 4 is in close contact with the drug release layer 3 through a fine gap and is electrically connected to the micro-control circuit layer 2. When ROS free radicals that are harmful to eye tissue are detected, the layer transmits the information to the microprocessor. The microprocessor adjusts the working state of the heating circuit according to the preset algorithm and logic, thereby controlling the drug release rate. This intelligent control mechanism not only improves the treatment effect, but also effectively prevents potential side effects that may be caused by excessive drug release. Finally, the drug molecules act on the cornea through the gap on the ROS detection layer 4, realizing comprehensive management and treatment of eye health. This corneal contact lens that integrates microelectronics technology and medical care functions has brought disruptive innovation to the field of ophthalmic medicine. Furthermore, the microprocessor is connected to a temperature sensor, and the type of the temperature sensor is preferably a high-precision temperature sensor AS621, which can provide high-precision temperature measurement results with an error range of ±0.2°C. It has low power consumption characteristics, and the current consumption in standby mode is only 1.2μA, which is very suitable for battery-powered portable devices. AS621 uses a miniaturized DFN package with a size of only 2mmx 2mm, which is easy to integrate into various compact electronic devices, and the eye area is 4-5 square centimeters. The contact lens of the present application is adapted to the eye, so the high-precision temperature sensor AS621 can be placed in the micro-control circuit layer. Alternatively, other miniature temperature sensors can be used, which is already a relatively mature technology and will not be repeated here.

[0034] Optionally, the ROS detection layer 4 is an electrochemical biosensor coated with ROS biorecognition molecules; when the ROS biorecognition molecules bind to the ROS, the electrochemical biosensor produces an electrochemical reaction and converts it into an electrical signal that can be measured by the microprocessor, and the microprocessor calculates the existence and concentration information of the ROS.

[0035] Optionally, the electrochemical biosensor comprises: a substrate with distributed gaps, an electrode attached to the substrate, and a ROS biorecognition molecule coated on the electrode, and the electrochemical reaction comprises: charge transfer and / or current and / or potential change.

[0036] Optionally, the substrate is in a disc-shaped spiral structure and is attached to the drug release layer 3 , and spiral coil-shaped gaps are distributed on the disc-shaped spiral structure, and the drug molecules act on the cornea through the spiral coil-shaped gaps.

[0037] When the concentration of ROS needs to be monitored, the ROS detection layer 4 appears in the form of an electrochemical biosensor, which is specially designed to recognize and bind to ROS. On the surface of the sensor, a layer of ROS biorecognition molecules is coated, which can react specifically with ROS. Once the binding occurs, the electrochemical biosensor converts this biochemical reaction into electrical signals, which are then captured and interpreted by the microprocessor, thereby calculating the presence and concentration information of ROS as the sensing result.

[0038] Specifically, electrochemical biosensors are made up of several core components. The first is a substrate with tiny gaps that not only optimize the performance of the sensor but also improve its sensitivity. On top of the substrate, there is a layer of electrodes, which act as a medium for electrochemical reactions and are responsible for transferring electrons. The ROS biorecognition molecules covering the surface of the electrodes serve as a bridge for the interaction between the sensor and ROS. When ROS bind to these molecules, a series of electrochemical reactions are triggered, such as charge transfer, current changes, or potential fluctuations. The electrical signals generated by these reactions will be captured and analyzed by the microprocessor.

[0039] In particular, in some applications, the substrate of the electrochemical biosensor is designed as a disc-shaped spiral structure, which not only enhances the surface area of ​​the sensor and improves the contact efficiency with ROS, but also can fit closely with other medical devices (such as drug release layer 3). Through the spiral gap, drug molecules can act on the cornea more effectively, thereby achieving more precise treatment and less side effects. This design makes the ROS detection layer not only a simple sensor, but also a treatment and monitoring unit that integrates multiple functions.

[0040] Optionally, when the microprocessor detects the presence of the ROS, it starts the heating circuit and sets the heating temperature according to the ROS concentration, the higher the concentration, the higher the heating temperature.

[0041] Optionally, the micro-control circuit layer 2 is covered with a packaging film 1, and the packaging film 1 and the substrate are made of a material with hydrophilic and oxygen-permeable properties.

[0042] Optionally, the drug molecules include inhibitors MCC950 and epidermal growth factor EGF, the inhibitors MCC950 and epidermal growth factor EGF are mixed with thermal phase change materials to form a thermal phase change material layer and are closely attached to the heating circuit, the thermal phase change material layer undergoes phase change when heated by the heating circuit, and the speed of the phase change is controlled by controlling the heating temperature to adjust the release rate of the drug molecules. Specifically, the thermal phase change material layer includes a polydimethylsiloxane (PDMS) substrate and a hydrogel, the drug molecules are mixed in the hydrogel, and there are one or more microcavities in the PDMS substrate, with a diameter size ranging from 100 to 200 μm. Specifically, a droplet template method can be used to form a microcavity with an opening, such as using a surface tension liquid such as water or glycerol to produce a spherical microcavity, and the drug-loaded hydrogel releases the drug through one or more narrow openings of multiple microcavities. During the manufacturing process, PDMS and the drug-loaded hydrogel are polymerized simultaneously to ensure that the hydrogel matrix is ​​embedded in the microcavity during the curing process. The drug-loaded hydrogel matrix is ​​initially in a dehydrated state and expands when in contact with an aqueous environment to facilitate drug delivery. The hydrogel releases drug molecules faster when heated.

[0043] In one embodiment, the hydrogel monomers include, but are not limited to, hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA), N-vinyl pyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), gelatin, alginate, cellulose, and the like.

[0044] Optionally, the micro-control circuit layer 2 also includes a micro power source 22, and is electrically connected to the heating circuit and the ROS detection layer 4 respectively through the microprocessor. When the microprocessor calculates that the rate of change of the ROS concentration is less than a preset value, the ROS detection layer 4 is continuously released with a current of a predetermined duration to remove the reactants. Specifically, during the monitoring process, the microprocessor will receive and parse the data from the ROS detection layer 4 in real time. When it is detected that the rate of change of the ROS concentration is lower than a preset safety threshold, the microprocessor will respond quickly and apply a current pulse of a predetermined duration to the ROS detection layer 4. The role of this current pulse is that it can effectively remove the reactants that may accumulate on the detection layer, ensuring that the sensitivity and accuracy of the detection layer are maintained. Through this fine current control, not only the efficient operation of the equipment is ensured, but also the accuracy and reliability of the data are guaranteed.

[0045] Optionally, the material having hydrophilic and oxygen-permeable properties is a hydrogel.

[0046] In order to further improve the comfort and adaptability of the cornea, the outer surface of the arc-shaped surface is also covered with a soft, biocompatible silicone layer. This silicone layer not only provides a comfortable wearing experience, but also prevents the corneal contact lens from sliding on the eyeball, ensuring that the drug molecules can act on the cornea accurately and stably.

[0047] In order to monitor the state of the contact lens and the drug release in real time, the microprocessor also has a wireless communication function and can transmit data with external devices. In this way, doctors or users can obtain information such as the working state of the contact lens, the drug release rate, and the ROS level of the cornea in real time, so as to carry out more accurate treatment and care.

[0048] The external device can be a smart phone, a tablet computer or a dedicated medical monitoring device. These devices communicate with the contact lens wirelessly, receive and display the data transmitted by the contact lens, and provide a user-friendly interface for doctors or users to view and analyze.

[0049] In order to further improve the intelligence level of corneal contact lenses, the microprocessor also has an adaptive learning function. It can automatically adjust the drug release strategy according to the user's corneal ROS level change history, drug release rate adjustment history, and treatment effect information to achieve the best treatment effect.

[0050] In order to ensure the safety and reliability of the corneal contact lens, the microprocessor also has safety protection functions such as overheat protection, overcurrent protection and battery power monitoring. Once an abnormality is detected, the microprocessor will immediately take corresponding measures, such as shutting down the heating circuit, cutting off the power supply, etc., to prevent damage to the cornea.

[0051] In order to extend the service life of the contact lens and facilitate maintenance, the microprocessor also has a self-cleaning function. It can control the heating circuit to generate a short high-temperature pulse to clean the residues on the drug release layer 3 and the ROS detection layer 4, thereby keeping the contact lens clean and stable in performance.

[0052] According to another aspect of the present application, the present application also provides a method for sustained release of ocular drugs for the corneal contact lens as described above, the method comprising: using the ROS detection layer 4 to detect ROS, and generating an electrical signal to a microprocessor; the microprocessor calculates the existence and concentration information of the ROS based on the received electrical signal; when the microprocessor detects the presence of the ROS, the microprocessor starts the heating circuit to heat the drug release layer 3 to a predetermined temperature or turns off the heating circuit to control the release rate of the drug molecules according to the concentration information, and the released drug molecules act on the cornea through the gaps in the ROS detection layer 4, and when the microprocessor calculates that the rate of change of the ROS concentration is less than a preset value, the microprocessor continuously releases an electric current for a predetermined period of time to the ROS detection layer 4.

[0053] When the ROS biorecognition molecule binds to the ROS on the contact lens, the electrochemical biosensor will immediately undergo an electrochemical reaction to generate a measurable electrical signal. These electrical signals are captured and interpreted by the microprocessor to accurately calculate the presence or absence of ROS and its concentration information.

[0054] In the design of the electrochemical biosensor, we specially selected a substrate material with excellent conductivity and evenly distributed tiny gaps on its surface. The electrodes are closely attached to these gaps, and the ROS biorecognition molecules are coated on the electrode surface to ensure efficient charge transfer and current changes. This design not only improves the sensitivity and accuracy of the sensor, but also ensures a rapid response to the detection results.

[0055] When the microprocessor detects the presence of ROS, it automatically adjusts the temperature of the heating circuit according to the ROS concentration. The heating temperature can be calculated based on factors such as ROS concentration, concentration change rate, and preset basal temperature. For example, when the ROS concentration is higher than the threshold, or the concentration change rate is higher than the threshold, heating is performed based on the preset ROS concentration-temperature correspondence table, or the preset concentration change rate-temperature correspondence table on the basis of the basal temperature. In this way, we can achieve precise control of the drug release rate and ensure that the drug can act on the cornea at the predetermined rate and dose.

[0056] In addition, we have specially designed a drug release layer 3, which contains a variety of drug molecules, such as the inhibitor MCC950 and epidermal growth factor EGF. These drug molecules are mixed with thermal phase change materials. When the heating circuit is activated, the thermal phase change material undergoes a solid-liquid phase change, thereby controlling the release rate of the drug molecules. In this way, we can flexibly adjust the drug release rate and dosage according to the health status of the cornea and the treatment needs.

[0057] In order to ensure the comfort and safety of corneal contact lenses, we use hydrophilic and oxygen-permeable hydrogel materials to make encapsulation films 1 and substrates. These materials not only have good biocompatibility, but can also effectively prevent the loss of water and oxygen, thereby keeping the cornea moist and breathing smooth.

[0058] As an optional implementation, when the microprocessor detects that the rate of change of ROS concentration is lower than a preset value, it will automatically release a current for a predetermined time to the ROS detection layer 4 to remove possible accumulated reactants and restore the detection performance of the sensor. This intelligent maintenance mechanism ensures the long-term stability and reliability of the corneal contact lens.

[0059] In the field of modern biomedicine, research on corneal health monitoring and disease treatment is becoming increasingly in-depth. The present invention relates to a corneal contact lens, which can not only detect ROS in corneal tissue, but also intelligently regulate drug release according to the detection results, thereby achieving precise management of eye health.

[0060] The core component of the corneal contact lens is an electrochemical biosensor that can sense the presence of ROS in corneal tissue and calculate its concentration. The sensor design cleverly utilizes the electrochemical reaction between the electrode and the ROS biorecognition molecule, which includes charge transfer, current and / or potential changes, thereby generating quantifiable electrical signals. After receiving these electrical signals, the microprocessor analyzes and obtains the specific concentration information of ROS through complex algorithms.

[0061] In the present invention, the design of the electrochemical biosensor is unique. It includes a disc-shaped spiral structure substrate with small gaps, which is specially designed to increase the contact area with the drug release layer 3 and promote the drug molecules to act on the cornea through the spiral coil-shaped gaps. In addition, the electrodes attached to the substrate are coated with ROS biorecognition molecules, which can specifically recognize and bind to ROS in corneal tissue, thereby triggering an electrochemical reaction.

[0062] In terms of drug release mechanism, the present invention uses a heating circuit that can automatically adjust the heating temperature when the presence of ROS is detected. This design ensures that the drug can be released at an appropriate rate and dosage according to the actual needs of the cornea.

[0063] The specially designed drug release layer 3 contains drug molecules such as inhibitor MCC950 and epidermal growth factor EGF, which are mixed with thermal phase change materials. When the heating circuit is activated, the thermal phase change material undergoes a solid-liquid phase change, and this process can be used to adjust the release rate of drug molecules. This intelligent drug release design allows the corneal contact lens to flexibly adjust the rate and dosage of drug release according to eye health conditions and treatment needs.

[0064] The material selection of corneal contact lenses uses hydrogel materials with hydrophilic and oxygen-permeable properties to make the packaging film 1 as a substrate. These materials not only have good biocompatibility, but also can effectively prevent the loss of water and oxygen, keep the cornea moist and breathe smoothly, thereby ensuring the comfort and safety of wearing.

[0065] Finally, the present invention also includes an intelligent maintenance mechanism. When the microprocessor detects that the rate of change of ROS concentration is lower than a preset value, it will automatically release a current for a predetermined period of time to the ROS detection layer 4 to remove possible accumulated reactants and restore the detection performance of the sensor. This intelligent maintenance mechanism ensures the long-term stability and reliability of the corneal contact lens and provides strong technical support for eye health monitoring and treatment.

[0066] In addition, the present application also provides an intelligent reminder function. When the micro-control circuit layer 2 senses the electrical signal and determines that the inflammatory factor exceeds the preset threshold, it will trigger the alarm module to send a reminder signal to remind the user to replace the corneal contact lens or seek medical treatment in time. This intelligent reminder function can effectively improve the user's attention to eye health and the timeliness of treatment.

[0067] In summary, the method for sustained release of ocular drugs through corneal contact lenses provided in this application combines multiple technologies such as biosensors, micro-control circuits, drug storage and release, and remote monitoring, which can achieve rapid and accurate detection of ocular inflammatory factors, and provide users with personalized eye health management and treatment plans through intelligent reminders and drug release control.

[0068] It is obvious to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and that the present application can be implemented in other specific forms without departing from the spirit or basic features of the present application. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-restrictive, and the scope of the present application is defined by the attached claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims are included in the present application. Any figure mark in the claims should not be regarded as limiting the claims involved. In addition, the terms used in the embodiments of the present application are for the purpose of describing specific embodiments only and are not intended to limit the present invention.

[0069] It should be noted that the terms "first", "second", etc. in the specification and claims of the present application and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. The singular forms of "a", "an" and "the" used in the embodiments of the present application are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0070] In addition, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or apparatus that includes a series of steps or elements is not necessarily limited to those steps or elements explicitly listed, but may include other steps or elements not explicitly listed or inherent to such process, method, product, or apparatus.

[0071] In the description of the present application, unless otherwise specified, " / " indicates that the objects associated before and after are in an "or" relationship, for example, A / B can represent A or B; "and / or" in the present application is only a kind of association relationship describing the associated objects, indicating that there can be three relationships, for example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone, where A and B can be singular or plural. Depending on the context, the words "if" or "if" as used herein can be interpreted as "at the time of" or "when" or "in response to determination" or "in response to detection". Similarly, depending on the context, the phrases "if it is determined" or "if (stated condition or event) is detected" can be interpreted as "when determined" or "in response to determination" or "when (stated condition or event) is detected" or "in response to detection (stated condition or event)".

[0072] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person of ordinary skill in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features thereof may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A corneal contact lens, characterized in that: include: The contact lens is a multi-layer structure with an arc-shaped surface, and the curvature of the arc-shaped surface matches the curvature of the cornea; The multilayer structure comprises: a micro-control circuit layer, a drug release layer and a ROS detection layer; The micro-control circuit layer includes a microprocessor and a heating circuit, and the microprocessor controls the heating circuit to heat to a predetermined temperature or to be turned off; The drug release layer is a thermal phase change material layer mixed with drug molecules and adhered to the micro-control circuit layer, and releases drug molecules when heated by the heating circuit; wherein the drug molecules include inhibitor MCC950 and epidermal growth factor EGF, the thermal phase change material layer includes a polydimethylsiloxane (PDMS) substrate and a hydrogel, the drug molecules are mixed in the hydrogel, the PDMS substrate has one or more microcavities with openings, and the diameter size ranges from 100 to 200 μm, the drug-loaded hydrogel releases the drug through one or more narrow openings of the multiple microcavities, the drug-loaded hydrogel matrix is ​​initially in a dehydrated state and expands when in contact with an aqueous environment to facilitate drug delivery, and the hydrogel accelerates the release of drug molecules when heated; The ROS detection layer has gaps distributed thereon, is adhered to the drug release layer, and is electrically connected to the micro-control circuit layer; When the ROS detection layer detects ROS, it is sensed by the microprocessor, and the microprocessor controls the release rate of the drug molecules by controlling the heating circuit to heat to a predetermined temperature or turning off the heating circuit according to the sensed result, and the drug molecules act on the cornea through multiple gaps; Wherein, the ROS detection layer is an electrochemical biosensor, on which ROS biorecognition molecules are coated; when the ROS biorecognition molecules bind to the ROS, the electrochemical biosensor generates an electrochemical reaction and converts it into an electrical signal that can be measured by the microprocessor, and the microprocessor calculates the existence and concentration information of the ROS; The electrochemical biosensor comprises: a substrate with gaps distributed therein, a gold wire electrode attached to the substrate, and alternating layers of cytochrome c and polyaniline (sulfonic acid) coated on the gold wire electrode; wherein cytochrome c is a ROS biorecognition molecule, and the electrochemical reaction comprises: charge transfer and / or current and / or potential change; The substrate is in a disc-shaped spiral structure and is attached to the drug release layer. Spiral coil-shaped gaps are distributed on the disc-shaped spiral structure, and drug molecules act on the cornea through the spiral coil-shaped gaps.

2. The contact lens according to claim 1, characterized in that: When the microprocessor detects the presence of the ROS, it starts the heating circuit.

3. The contact lens according to claim 1, wherein: The micro-control circuit layer is covered with a packaging film, and the packaging film and the substrate are made of materials with hydrophilic and oxygen-permeable properties.

4. The contact lens according to claim 3, characterized in that: The inhibitor MCC950 and epidermal growth factor EGF are mixed with a thermal phase change material to form a thermal phase change material layer and tightly attached to the heating circuit. The thermal phase change material layer undergoes a phase change when heated by the heating circuit, and the speed of the phase change is controlled by controlling the heating temperature to adjust the release rate of the drug molecules.

5. The contact lens according to claim 4, characterized in that: The micro-control circuit layer also includes a micro-power source, and is electrically connected to the heating circuit and the ROS detection layer through the microprocessor. When the microprocessor calculates that the ROS concentration change rate is less than a preset value, the microprocessor continuously releases current for a predetermined period of time to the ROS detection layer to remove reactants.

6. The contact lens according to claim 5, characterized in that: The material with hydrophilic and oxygen-permeable properties is a hydrogel.

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