Drug release implant

Abstract

Implant (1) comprising a microchip (2), a microchip (2) energy supply device (3) connected to the microchip (2), and a reservoir (4) adapted to store and repeatedly release an active substance, the microchip (2) having means (5) for causing a temperature change, the means (5) being thermally connected to the reservoir (4), characterized in that the means (5) are thermally connected to the reservoir (4). The reservoir (4) can be reversibly transferred from a first state (Z1) at a first temperature (T1) to a second state (Z2) at a second temperature (T2), the reservoir (4) storing the active substance in the first state (Z1) and releasing the active substance in the second state (Z2).

Description

Technical Field

[0001] The present invention relates to a drug-release implant for controlled release of an active substance, particularly for lowering intraocular pressure, a system comprising an implant and an external device for manipulating and / or reading the implant, and a method for releasing the active substance using the aforementioned implant or system. Background Technology

[0002] Glaucoma (Glaukom bzw. Grüner Star) is a disease caused by high intraocular pressure, leading to the death of nerve cells in the eye. Therefore, it is typically treated with intraocular pressure-lowering medications. Currently, this is usually done through topical medication, such as eye drops. However, this therapy has drawbacks: the reliability of patient-determined dosage and administration is limited, and local side effects may occur.

[0003] Therefore, as an alternative to such topical drug treatments, implants are increasingly used in existing technologies. These implants are placed inside the eye to be treated, creating an artificial drainage channel for aqueous humor or releasing the active substance contained within the implant into the eye as needed. Intraocular pressure fluctuates significantly, necessitating continuous monitoring of intraocular pressure and adaptation of drug dosage to pressure changes. This is typically achieved through an IOD sensor (intraocular pressure sensor) integrated into the implant.

[0004] To achieve controlled, on-demand release of active substances, specific release mechanisms are required for drug-loaded delivery systems—such as implants. Various release mechanisms are known in the prior art. For example, US 2018 333296 A1 discloses an implant in which the release of its contained active substance is triggered by light, heat, ultrasound, radio frequency, laser, etc. External stimuli should be able to break, puncture, or otherwise damage the sealing measures of the reservoir containing the active substance, thereby allowing the active substance to flow out of the reservoir.

[0005] US 6,527,762 B1 also discloses an implant in which a reservoir has a cap that is damaged by heating or otherwise altered, allowing all the active material contained within the reservoir to leak out. Here, the damage to the cap is achieved by the cap material expanding, contracting, or undergoing a phase change in response to temperature changes.

[0006] US 2022 273 556 A1 discloses an apparatus for controlled release of a therapeutically active substance, wherein the release of the entire active substance is triggered by irradiating an active substance reservoir with a near-infrared laser. Summary of the Invention

[0007] In view of the prior art, the object of the present invention is to provide an implant capable of controlled and particularly flexible release of an active substance contained therein. Furthermore, the object of the present invention is to provide a corresponding system and a method for applying the implant or system.

[0008] This invention achieves its objective by an implant comprising a microchip, a microchip power supply device connected to the microchip, and a reservoir adapted to store and repeatedly release an active substance, the microchip having a means for inducing a temperature change, the means being thermally connected to the reservoir, characterized in that the reservoir is reversibly transitioning from a first state at a first temperature to a second state at a second temperature, wherein the reservoir stores the active substance in the first state and releases the active substance in the second state.

[0009] The microchip is specifically used for networking all electronic components of the implant—e.g., sensors, devices for communicating with external devices, or, particularly, the aforementioned power supply devices connected to the microchip. Here, the microchip can also be a dedicated integrated circuit (ASIC), which is particularly simple and inexpensive to manufacture compared to separate circuits. The microchip also has a device for inducing temperature changes, which, together with the microchip, receives power through the connected power supply device. In this invention, the device for inducing temperature changes is understood as an element suitable for inducing positive or negative temperature changes (i.e., heating or cooling). Therefore, they can be, for example, Peltier elements that have a cooling effect when energized accordingly, or heating elements that have a heating effect. The device for inducing temperature changes is thermally connected to a reservoir containing the active material. Alternatively, as an alternative, the device for inducing temperature changes and the reservoir can be constructed as a single unit. For this purpose, the reservoir has a material sensitive to thermal effects, such that the reservoir stores the active material (i.e., does not release the active material) when in a first state at a first temperature, but releases the active material when in a second state at a second temperature. Here, according to the invention, it is particularly advantageous that the first temperature is the ambient temperature during implant use, while the second temperature, different from the first temperature, is generated by the device for inducing temperature change acting on the reservoir. Thus, by selectively manipulating the implant and correspondingly energizing the device for inducing temperature change, the reservoir can be switched from a first state to a second state. Here, according to the invention, the reservoir is configured such that when the device for inducing temperature change is turned off, the reservoir reaches its original first temperature and thus returns to the first state. Therefore, according to the invention, the reservoir has or is composed of a heat-affected material that exhibits different states or phases depending on temperature, thus allowing or preventing the outflow of substances according to the temperature.

[0010] A significant advantage of this implant is that the release of the active substance can be activated on demand, but can also be interrupted, allowing the remaining active substance in the reservoir to be released at a later time. Therefore, compared to known implants, the implant according to the invention can hold more active substance without causing overdose due to the simultaneous release of the entire reservoir contents. Traditional drug-release implants release a large amount of active substance in the initial stage, which, at best, is wasted and becomes unusable later, thus reducing the effective duration. In the worst case, high doses can cause harm.

[0011] In principle, the size of the implant according to the invention is limited so that it can be placed in the vitreous body, suprachoroidal space, subconjunctival space, or anterior chamber angle of the eye. For this purpose, its height should be less than 500 micrometers. It is also advantageous that the implant is designed to be at least partially flexible and curved, with its curvature adapted to the radius of curvature of the eye to be treated. Similarly, since it is placed within the human eye, it is advantageous if the implant is surrounded by a biocompatible polymer (particularly silicone, phenelzine, or polyimide). The implant according to the invention can also be combined with known implants for other ocular uses (e.g., intraocular lenses, anterior chamber lenses, or suprascleral or minimally invasive glaucoma drainage implants). Here, the aforementioned known implants can be implanted together with the implant according to the invention, or they can be physically integrated with the implant according to the invention, particularly as a single unit, or integrated into the implant according to the invention.

[0012] In another advantageous embodiment of the invention, the implant according to the invention is sized to allow it to be placed within the posterior chamber or lens capsule. In a further development of the invention, it is proposed that the microchip power supply device be operable via an external device, and particularly formed as at least one induction coil. If the power supply device is operable via an external device, it is advantageous that the energy supply to the implant and the release of active substances can be achieved through targeted manipulation (particularly by an external user). A particularly simple method of manipulation is through an electromagnetic field that induces a current in the induction coil of the implant, thereby powering the microchip and all its connected components. However, according to the invention, the use of other types of energy sources, such as lasers, infrared light, or magnets, is also possible.

[0013] In one embodiment of the invention, it is proposed that the device for inducing temperature changes comprises an ohmic heating element, an overload protection circuit, a Peltier element, a Zener diode array, a resistor matrix circuit, a conductive polymer matrix, and / or a passive resonant circuit system. In particular, the overload protection circuit is a common component of microchips—especially ASICs. Here, the microchip is powered by a power supply device, wherein excess electrical energy input to the microchip is discharged / dissipated as heat through the overload protection circuit. The Zener diode array, resistor matrix circuit, and conductive polymer matrix serve similar functions. Conversely, the Peltier element can also have a cooling effect. The passive resonant circuit system generates heat when the resonant frequency is reached. Within the framework of the invention, the passive resonant circuit can be designed to be severely detuned relative to the operating frequency in a static state, and a capacitor integrated on the ASIC can be turned on when needed, the size of which is designed so that the resonant frequency of the passive resonant circuit is within the operating frequency range, thereby generating heat or cold.

[0014] In a further development of the invention, it is proposed that the reservoir comprises a thermoresponsive material, particularly a thermoresponsive polymer or thermoresponsive nanoparticles, especially poly(N-isopropylacrylamide) or lipid-based nanoparticles, and particularly that the reservoir is composed of one of these materials. In principle, the advantage of thermoresponsive materials is that they undergo structural changes or phase transitions with temperature changes, and thus can be manipulated by temperature variations. Reservoirs typically contain active substances within their cavities, and therefore structural changes can lead to the opening of the cavities. Simultaneously, returning to the initial temperature causes the structure to change again, thereby advantageously leading to the restoration of the structure of the closed cavity. Thermoresponsive polymers or nanoparticles have proven particularly advantageous because their composition can be modified and supplemented by copolymers to set the lower critical solution temperature, i.e., the initial temperature at which the polymer undergoes a phase transition and releases the contained active substances. Specifically, poly(N-isopropylacrylamide)-based nanoparticles or lipid-based nanoparticles such as liposomes and solid lipid nanoparticles (SLNs) have proven particularly advantageous in drug delivery (administration) applications.

[0015] In one embodiment of the invention, it is proposed that the reservoir has multiple chambers, wherein, in particular, each chamber is individually reversibly transition from a first state at a first temperature to a second state at a second temperature. According to the invention, the multiple chambers can be understood both as a reservoir having multiple adjacent chambers and as multiple chambers spatially separated from each other. This is particularly advantageous if these different chambers can be individually manipulated so that the desired dosage can be more precisely personalized. Similarly, according to the invention, each chamber can have a single dose, such that manipulation of one chamber results in the complete emptying of that chamber.

[0016] In a further development of the invention, it is proposed that the reservoir is constructed and arranged to cover, in particular, to seal the device for inducing temperature changes. This advantageously achieves the protection of the device for inducing temperature changes (as previously mentioned, which may be an electronic / electrical component) from liquids and other environmental influences. Here, according to the invention, the device for inducing temperature changes is located on the microchip, and the reservoir can also seal the rest of the microchip.

[0017] In one embodiment of the invention, it is proposed that the device for inducing temperature change is doped, coated, and / or loaded with an active material. In this case, the device for inducing temperature change is particularly preferably integrated with the reservoir. Thus, the temperature change can act directly on the thermally responsive structure without the need for a special heat conductor or other similar material. In this case, the temperature change leads to the decoupling of the active material from the device for inducing temperature change, thereby releasing the active material. Relatedly, within the framework of the invention, it is conceivable, for example, to load the polymer with metal particles.

[0018] In a further development of the implant according to the invention, it is proposed that the implant has at least one sensor, particularly at least one IOD sensor and / or temperature sensor. The sensor can monitor important environmental parameters, particularly those related to determining the timing and dosage of the active substance to be released. For the release of an intraocular pressure-lowering active substance, whether the intraocular pressure deviates from normal and the degree of deviation are crucial for decision-making. Furthermore, the therapeutic effect of the active substance used can be monitored. The temperature sensor is specifically used to monitor the device for inducing temperature changes and to check whether it operates as intended by the user. This at least one sensor is also powered by the microchip power supply.

[0019] However, within the framework of this invention, it is also possible to implement an embodiment in which intraocular pressure measurement is performed by a separate implant. In these embodiments of the invention, the drug-release implant itself has only at least one temperature sensor. The signal characterizing intraocular pressure is generated in these embodiments by a second implant designed separately from the drug-release implant.

[0020] In one embodiment of the invention, the implant is provided with means for communicating with an external device. Such means are used to transmit data to the external device, thus allowing data, such as data collected from sensors or data regarding the reservoir filling status, to be sent to the external device for evaluation by the user. Monitoring parameters native to the implant is particularly advantageous for personalized planning and adaptation of patient treatment. A significant advantage is that the communication means is activated only when a corresponding power supply is available, ensuring data can always be read when needed. However, according to the invention, data can also be transmitted periodically, so that operational errors do not affect treatment. According to the invention, communication with the external device is particularly non-contact, thus allowing data to be read without removing the implant from the eye. For this purpose, in one embodiment, the communication means is configured as an antenna, which in particular emits electromagnetic waves that can be read by the external device. In this embodiment, the communication means can also advantageously be used to transmit energy to the implant.

[0021] In a further development of the invention, it is proposed that the first temperature corresponds to the average body temperature of the human eye, and / or the second temperature corresponds to a temperature ≥38°C, particularly between 39°C and 42°C. In this way, the reservoir stores the active substance in the first state, preventing accidental leakage at the average body temperature of the human eye. More precisely, the aim is to ensure that the active substance only leaks from the reservoir upon conscious activation, i.e., upon initiation of the implant's energy supply. To this end, the selection of the second temperature relative to the first temperature should ensure that the temperature difference reliably triggers the release of the active substance while avoiding accidental triggering due to slight fluctuations in eye temperature. Simultaneously, the second temperature as the trigger temperature should be as close as possible to the average temperature of the human eye to avoid causing discomfort or even damage to the patient's eye. In this regard, practice has shown that temperatures between 39°C and 42°C are particularly advantageous and meet the above criteria.

[0022] Furthermore, the object of the present invention is also achieved by a system for the controlled release of a therapeutically active substance, comprising an implant according to the foregoing embodiments and an implant manipulation and / or reading device. The implant manipulation and / or reading device is used to activate the implant (particularly its power supply device) and / or receive data from the implant. If the implant has an induction coil as a power supply device, as in one embodiment, an electromagnetic field can be generated by the device manipulating the implant, thereby inducing a current in the induction coil of the implant. According to the invention, other manipulation devices (manipulation measures) may also be employed, such as lasers or near-infrared light. For implant reading, the device is particularly configured as a transceiver suitable for contactless data transmission, such as via Bluetooth, NFC, RFID, or other wireless technologies.

[0023] In implementations of this system, it is proposed that the implant manipulation and / or reading device is a handheld reader, a reading unit integrated into eyeglasses, or an adhesively fixed reading unit, particularly a reading unit integrated into an eye patch. According to the invention, a smartphone can also serve as an implant reading device, whereby data is received by the smartphone, for example via Bluetooth, and can be evaluated via an application (App). Handheld readers are particularly suitable, but eyeglasses are also appropriate as manipulation devices compared to smartphones because they can be brought close to the eye with the implant without problems, and several feasible options are provided by supplementing them with devices suitable for generating and emitting electromagnetic fields, lasers, infrared light, or magnetic fields.

[0024] Further developments to this system propose sending users regular intraocular pressure measurement reminders and / or information regarding the dosage of the released active substance. Such reminders are particularly important for ensuring treatment effectiveness and calculating the actual required dosage. According to the invention, this reminder is delivered via an application on the user's or patient's smartphone, or alternatively, if the user uses a handheld reader as an implant manipulation and / or reading device, the signal is sent to that handheld reader. If the implant has an internal power supply, the signal can also be emitted from the implant.

[0025] Finally, the object of the present invention is achieved by a method for controlled release of a therapeutically active substance, particularly using an implant or system according to the foregoing embodiments, comprising the steps of: heating or cooling the device for inducing a temperature change; transferring the temperature change generated on the device for inducing the temperature change to a reservoir, causing the reservoir to change from a first state at a first temperature to a second state at a second temperature, and thermally triggering the release of an active substance contained in at least one reservoir; terminating the release of the active substance stored in at least one reservoir by changing the reservoir from the second state at the second temperature to the first state at the first temperature, wherein the reservoir is cooled by stopping the temperature change of the device for inducing the temperature change according to the first method step.

[0026] In the first step of heating or cooling the device for inducing temperature change, energy is supplied to enable the temperature change. The exact function of the device for inducing temperature change depends on its design and, depending on the specific implementation, may be an ohmic heating element, an overload protection circuit, a Peltier element, a Zener diode array, a resistor matrix circuit, a conductive polymer matrix, and / or a passive resonant circuit system. This temperature change is transferred to the reservoir. This transfer is particularly advantageously via thermal conduction. Alternatively, the reservoir and the device for inducing temperature change may be constructed integrally or in close contact with each other, so that the temperature change is transferred through their materials. Here, the temperature change should be selected such that it causes the reservoir to transition from a first state of storing active material to a second state of releasing active material. The energy supply to the microchip and the device for inducing temperature change is only shut off after a specific amount or dose of active material, individually determined according to the treatment requirements, has been released. Thus, the temperature change stops / ends, and the reservoir returns to the first temperature, i.e., the local ambient temperature of the eye. In this way, the reservoir returns to the first state, and thus it no longer releases the active substance stored therein. Accordingly, the reservoir can reversibly switch between the first and second states, so the reservoir does not need to be completely emptied, and the dose of active substance released is controllable. The above steps can be repeated as needed until the reservoir is empty.

[0027] In an embodiment of this method, it is proposed that, in a first method step, the device for inducing a temperature change is heated by over-supplying energy to the microchip via a power supply device. By over-supplying the microchip, the device for inducing a temperature change converts excess current not consumed by other components of the microchip (such as sensors) into heat energy. In commercial microchips (especially ASICs), overload protection circuits are typically provided to protect them from high voltage and voltage spikes. This circuit converts the intentionally provided excess electrical energy input into heat energy, thereby causing a temperature change. Here, other circuits—such as a resistor matrix—can also produce the same effect and induce a temperature change upon excessive electrical energy input. Therefore, this embodiment is particularly advantageous due to its simplicity. Those skilled in the art will know that the implant also possesses a “real” protection circuit that intervenes when the implant is over-supplyed (over-powered) during operation without the intention of releasing active material.

[0028] In a further development of this method, it is proposed that the mass of the released active substance be controlled by the duration of the reservoir being in the second state and / or the temperature difference between the first and second temperatures, particularly via the implant manipulation and / or reading device. If the reservoir is held in the second state for a longer duration, the active substance continues to be released at the same rate for that longer duration. And when the temperature difference measured by the sensor is greater, a greater amount of active substance is released in the same amount of time. Accordingly, according to the invention, a longer duration of the second state and a greater temperature difference can also be combined. This effect on the amount of released active substance is achieved, particularly by the user or automatically via software, through the implant manipulation and / or reading device, thereby allowing treatment to be personalized and dynamically adjusted to the patient's needs. In particular, in this regard, a device according to any one of claims 1 to 12, as described in German publication DE 10 2019 126 959 A1, can be used, the device comprising a valve for changing intraocular pressure in vivo.

[0029] In this method, it is proposed that the amount of active substance to be released be calculated based on the intraocular pressure measured by at least one sensor. Especially in the treatment of glaucoma, it is necessary to lower the intraocular pressure as much as possible. For this purpose, an intraocular pressure-lowering active substance is used. In order to appropriately adjust the degree of intraocular pressure reduction, it is necessary to measure the intraocular pressure and release only this amount of active substance, i.e., to bring the elevated intraocular pressure close to the ideal value. Particularly in the case of continuous or periodic monitoring of intraocular pressure, the amount of active substance to be released can be periodically adjusted during the measurement process. Accordingly, the treatment can be personalized and tailored to the patient's needs. Attached Figure Description

[0030] The present invention will be described by way of example through preferred embodiments in conjunction with the accompanying drawings, and other advantageous details can be learned from the various figures in the drawings.

[0031] Here, components with the same function are labeled with the same reference numerals.

[0032] The attached diagram shows the details below:

[0033] Figure 1 : A schematic diagram of the implant according to the invention in a first embodiment.

[0034] Figure 2 : A schematic diagram of the implant according to the invention in a second embodiment.

[0035] Figure 3 : A schematic diagram of a system comprising an implant and an implant manipulation and / or reading device according to the present invention.

[0036] Figure 4 A simplified diagram illustrating the possible states of the storage device. Detailed Implementation

[0037] Figure 1A schematic diagram of an implant 1 according to a first embodiment of the invention is shown. The structure, shape, and size of the implant 1 allow it to be placed in the human eye without significant limitations for the patient. The implant 1 includes a microchip 2, which ensures the basic functions of the implant 1. For this purpose, it is sufficient that the microchip 2 is constructed as an ASIC. The energy required for the normal operation of the microchip 2 is provided by a power supply device 3, which, in the illustrated embodiment, is formed as an induction coil. The power supply device 3 can be controlled by an external device, which, in the illustrated embodiment, generates an electromagnetic field that induces a current in the induction coil. In addition to the microchip 2, the power supply device 3 also powers any sensors 7 and communication devices 8 connected to the microchip 2, which are schematically depicted together here. The sensors 7 are specifically designed for detecting environmental parameters, wherein the communication devices 8 can both transmit the detected environmental parameters to an external device and control the sensors 7 and the rest of the microchip 2 via the external device. The microchip 2 also has a device 5 for inducing temperature changes, which is only schematically shown here. The device can be, for example, a Peltier element, or an overload protection circuit that converts the current from the power supply device 3 into heat energy via the microchip 2. To this end, an excessive power supply is intentionally forced onto the implant 1, such that the microchip 2, sensor 7, and communication device 8 are supplied with sufficient current, while the remaining excess current is utilized by the device 5 for inducing temperature changes. The temperature of the reservoir 4 is measured by a temperature sensor 5a (not shown). This temperature change is transmitted to the reservoir 4, which is thermally connected to the device 5 for inducing temperature changes. Due to this temperature change, the reservoir 4 transitions from a first state (storing the active substance contained therein) to a second state (releasing the active substance). Similarly, a certain amount of basal drug release (Grund-Freigabe von Wirkstoff) may also occur without heating the reservoir, which may have therapeutic advantages in some applications. Figure 2 A schematic diagram of the implant 1 according to the invention in a second embodiment is shown. In this embodiment, the reservoir 4 is divided into multiple chambers 6, each chamber capable of containing a certain amount of active material. Each chamber 6 can independently and reversibly transition from a first state to a second state, wherein the device 5 for inducing temperature changes is thermally connected to each chamber 6. Therefore, in the illustrated embodiment, the chambers 6 and the device 5 for inducing temperature changes are spatially separated, with each device 5 thermally connected to one chamber 6. This embodiment allows for individual manipulation of each chamber 6, enabling more flexible and personalized adjustments to the treatment according to patient needs and treatment goals.

[0038] Figure 3A schematic diagram of a system according to the present invention, comprising an implant 1 and an implant 1 control and / or reading device 9, is shown. The implant 1 control and / or reading device 9 communicates with both the power supply device 3 and the sensor 7 and the communication device 8. Thus, in this embodiment, the implant 1 control and / or reading device 9 emits an electromagnetic field that induces a current in the power supply device 3, which is in the form of an induction coil, thereby providing energy to the implant 1. Simultaneously, upon the commencement of energy supply, the sensor 7 detects environmental parameters, which are transmitted non-contactly to the implant 1 control and / or reading device 9 via the communication device 8, particularly via Bluetooth, RFID, NFC, or other wireless technologies.

[0039] Figure 4 A highly simplified schematic diagram of the possible states of reservoir 4 is shown. Thus, in a highly simplified representation: state Z1 corresponds to a first temperature T1, and state Z2 corresponds to a second temperature T2. Reservoir 4 stores the active substance contained therein in state Z1, and releases the active substance in state Z2. The first temperature T1 specifically corresponds approximately to the mean ocular temperature, while the second temperature T2 is a different temperature, the deviation being within a range that avoids harm to the patient while also preventing the reservoir 4 from accidentally transitioning to state Z2 due to normal temperature fluctuations. The double arrows shown between states Z1 and Z2 symbolically represent the reversibility of the transition between the two states of reservoir 4. Therefore, the release of the active substance is adjustable and does not depend on the size of the reservoir 4's reserve, eliminating the need to release all the active substance contained in reservoir 4 in a single dose (one-time). In practice, states 1 and 2 occur in ranges below the upper limit or above the lower limit.

[0040] List of reference numerals 1. Implant 2 microchips 3. Power supply device 4. Storage container 5. Devices for inducing temperature changes 5a Temperature Sensor 6 chambers 7 sensors 8 communication devices 9. Implant manipulation and / or reading device Z1 First State Z2 Second State T1 First Temperature T2 Second Temperature

Claims

1. An implant (1), comprising: The microchip (2), the microchip (2) power supply device (3) connected to the microchip (2), and the reservoir (4) suitable for storing and repeatedly releasing active substances, the microchip (2) having a device (5) for inducing temperature changes, the device being thermally connected to the reservoir (4), characterized in that the reservoir is reversibly capable of transitioning from a first state (Z1) at a first temperature (T1) to a second state (Z2) at a second temperature (T2), wherein the reservoir (4) stores active substances in the first state (Z1) and releases active substances in the second state (Z2).

2. The implant (1) according to claim 1, characterized in that, The microchip (2) power supply device (3) can be controlled by an external device and is specifically formed as at least one induction coil.

3. The implant (1) according to claim 1 or 2, characterized in that, The device (5) for inducing temperature change has an ohmic heating element, an overload protection circuit, a Peltier element, a Zener diode array, a resistor matrix circuit, a conductive polymer matrix, and / or a passive resonant circuit system.

4. The implant (1) according to claim 1, 2 or 3, characterized in that, The reservoir (4) has a thermoresponsive material, particularly a thermoresponsive polymer or thermoresponsive nanoparticles, especially preferably poly(N-isopropylacrylamide) or lipid-based nanoparticles, and is composed of one of these materials.

5. The implant (1) according to any one of the preceding claims, characterized in that, The reservoir (4) has a plurality of chambers (6), wherein, in particular, each chamber (6) is reversibly transitioning from a first state (Z1) at a first temperature (T1) to a second state (Z2) at a second temperature (T2) individually.

6. The implant (1) according to any one of the preceding claims, characterized in that, The reservoir (4) is configured and arranged to cover the device (5) for inducing temperature changes, and in particular to seal the device for inducing temperature changes.

7. The implant (1) according to any one of the preceding claims, characterized in that, The device (5) for inducing temperature changes is doped, coated, or loaded with an active substance.

8. The implant (1) according to any one of the preceding claims, characterized in that, The implant has at least one sensor (7), particularly at least one IOD sensor and / or temperature sensor.

9. The implant (1) according to any one of the preceding claims, characterized in that, The implant has a device (8) for communicating with external devices.

10. The implant (1) according to any one of the preceding claims, characterized in that, The first temperature (T1) corresponds to the average body temperature normally seen in the human eye, and / or the second temperature (T2) corresponds to a temperature ≥ 38 °C, particularly a temperature between 39 °C and 42 °C.

11. A system for controlled release of a therapeutically active substance, comprising an implant (1) according to any one of claims 1 to 10, and comprising an implant (1) manipulation and / or reading device (9).

12. The system according to claim 11, characterized in that, The implant (1) manipulation and / or reading device (9) is a handheld reader, a reading unit integrated into glasses, or an adhesively fixed reading unit, particularly a reading unit integrated into an eye patch.

13. The system according to claim 11 or 12, characterized in that, The system sends users regular reminders for intraocular pressure measurements and / or information about the dosage of the released active substance.

14. A method for controlled release of a therapeutically active substance, particularly using an implant (1) according to any one of claims 1 to 10 or a system according to any one of claims 11 to 13, comprising the following steps: a) Heating or cooling the device (5) used to induce a temperature change. b) The temperature change generated on the device (5) for inducing the temperature change is transmitted to the reservoir (4) to cause the reservoir to change from a first state (Z1) at a first temperature (T1) to a second state (Z2) at a second temperature (T2), and thermally triggers the release of at least one active substance stored in the reservoir (4). c) The release of active material stored in at least one reservoir (4) is terminated by changing the reservoir from a second state (Z2) at a second temperature (T2) to a first state (Z1) at a first temperature (T1), wherein the reservoir is cooled by stopping the temperature change of the device (5) for inducing the temperature change according to step a).

15. The method according to claim 14, characterized in that, In step a), the device (5) for inducing temperature change is heated by over-supplying energy to the microchip (2) through the power supply device (3).

16. The method according to claim 14 or 15, characterized in that, The quality of the released active substance is controlled by the duration of the reservoir (4) in the second state (Z2) and / or the temperature difference between the first temperature (T1) and the second temperature (T2), particularly via the implant (1) manipulation and / or reading device (9).

17. The method according to claim 14, 15 or 16, characterized in that, The amount of active substance to be released is calculated based on the intraocular pressure measured by at least one sensor (7).

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