Implant dispensing active substance

Abstract

An implant (1) having a microchip (2), means (3) connected to the microchip (2) and supplying energy to the microchip (2), and a reservoir (4) suitable for storing and repeatedly dispensing an active substance, wherein the microchip (2) has means (5) for bringing about a change of temperature, said means (5) being thermally connected to the reservoir (4), characterized in that the reservoir is reversibly transferrable from a first state (Z1) at a first temperature (T1) to a second state (Z2) at a second temperature (T2), wherein the reservoir (4) in the first state (Z1) stores the active substance and in the second state (Z2) dispenses the active substance.

Description

[0001] Drug-releasing implant

[0002] The present invention relates to a drug-releasing implant for the controlled release of an active substance, in particular an intraocular pressure-reducing active substance, a system comprising an implant and an external device for controlling and / or reading the implant and a method for releasing an active substance using an aforementioned implant or system.

[0003] Glaucoma is a disease in which nerve cells in the eye die due to high intraocular pressure. Accordingly, this disease is typically treated with intraocular pressure-lowering medications. It is common practice to administer such drugs as part of a topical medication regimen, for example, via eye drops. However, these methods have the disadvantage that dosage and administration by the patient are only partially reliable, and local side effects can occur.

[0004] As an alternative to such therapy with topical medication, implants are increasingly being used in the state of the art. These implants are inserted into the eye to be treated and either create an artificial aqueous humor outflow or, if necessary, release an active ingredient contained in the implant into the eye. The pressure in the human eye is subject to significant fluctuations, so the intraocular pressure must be constantly monitored and the medication dose adjusted accordingly. This is usually done using an IOP sensor (intraocular pressure sensor) integrated into the implant.

[0005] To enable controlled, on-demand release of the active ingredient, a specific release mechanism is required for drug-loaded drug delivery systems, such as an implant. Various release mechanisms are known in the prior art. For example, US 2018 333 296 A1 discloses an implant in which the release of an active ingredient contained within it is triggered by light, heat, ultrasound, radio frequency, laser, or similar. The external stimulus is intended to break, puncture, or otherwise damage a closure of the reservoir containing the active ingredient, allowing the active ingredient to escape from the reservoir.

[0006] US Pat. No. 6,527,762 B1 also discloses an implant in which the reservoir has a lid that is damaged or otherwise altered by heating such that the entire active ingredient contained in the reservoir can escape from the reservoir. Damage to the lid occurs through expansion, contraction, or phase changes of the lid material in response to the temperature change.

[0007] From US 2022 273 556 A1 a device for the controlled release of a therapeutic agent is known, in which the release of the entire agent is triggered by irradiation of the agent reservoir with an NIR laser.

[0008] In light of this prior art, the object of the invention is to provide an implant that enables a controlled and particularly flexible release of an active ingredient incorporated therein. Furthermore, the object of the invention is to provide a corresponding system and a method using such an implant or system.

[0009] The object of the invention is achieved by an implant comprising a microchip, means connected to the microchip for supplying energy to the microchip, and a reservoir which is suitable for storing and repeatedly releasing an active ingredient, wherein the microchip has means for inducing a temperature change which are thermally connected to the reservoir, in that the reservoir can be reversibly converted from a first state at a first temperature to a second state at a second temperature, wherein the reservoir stores the active ingredient in the first state and releases the active ingredient in the second state.

[0010] The microchip serves in particular to network all electronic components of the implant, such as sensors, means for communication with an external device, or in particular the aforementioned power supply means connected to the microchip. The microchip can also be an application-specific integrated circuit (ASIC), which is particularly simple and inexpensive to manufacture compared to individual circuits. The microchip also has means for inducing a temperature change, which are supplied with energy together with the microchip by the connected power supply means. The invention defines the means for inducing a temperature change as elements suitable for inducing a positive or negative temperature change, i.e., heating or cooling.They can thus be, for example, a Peltier element, which has a cooling effect when appropriately supplied with current, or a heating element with a heating effect. The means for inducing a temperature change are thermally connected to the reservoir, which holds the active ingredient. Alternatively, the means for inducing a temperature change and the reservoir can be designed as a single piece. For this purpose, the reservoir comprises a thermally influenceable material such that, in a first state at a first temperature, the reservoir stores the active ingredient, thus not releasing it, but in a second state at a second temperature, it releases the active ingredient.According to the invention, it is particularly advantageous if the first temperature is the ambient temperature of the implant in use, while the second temperature, which differs from the first temperature, is generated by the means for inducing a temperature change on the reservoir. Thus, with targeted control of the implant and appropriate energization of the means for inducing a temperature change, the reservoir can be specifically shifted from the first state to the second state. According to the invention, the reservoir is designed such that when the means for inducing a temperature change are switched off, it assumes the original first temperature and thus returns to the first state.For this purpose, according to the invention, the reservoir comprises or consists of such a thermally influenceable material that the material assumes different states or phases depending on the temperature and thus enables or prevents leakage depending on the temperature.

[0011] Such an implant has the particularly great advantage that the release of the active ingredient can be activated as needed, but at the same time the release can be interrupted so that the remaining active ingredient in the reservoir can be released at a later time. Thus, an implant according to the invention can absorb more active ingredient than known implants without leading to an overdose due to a single release of the entire contents of the reservoir. Conventional drug-releasing implants release a large amount of active ingredient in the initial phase, which is wasted at best and no longer available later, thus reducing the duration of effectiveness. In the worst case, the high doses cause damage.In principle, the dimensions of the implant according to the invention are limited in such a way that placement of the implant in the vitreous body, suprachoroidal space, subconjunctival space, or chamber angle of the anterior chamber of the eye is possible. For this purpose, it should have a height of less than 500 μm. It is also advantageous if the implant is at least partially flexible and curved, so that the curvature adapts to the radius of the eye to be treated. Likewise, due to its use in a human eye, it is advantageous if the implant is surrounded by a biocompatible polymer, in particular a silicone, parylene, or polyimide. A combination of the implant according to the invention with known implants for other applications in the eye is also possible, such as an intraocular lens, anterior chamber lens, or epibulbar or minimally invasive glaucoma drainage implants.The aforementioned known implants can be implanted together with the implant according to the invention, or they can be physically combined with the implant according to the invention, in particular as a one-piece unit, or integrated into the implant according to the invention.

[0012] In another advantageous embodiment of the invention, the dimensions of the implant according to the invention are selected such that placement in the posterior chamber or in the capsular bag is possible. In a further development of the invention, it is proposed that the means for supplying energy to the microchip can be controlled by an external device and are designed in particular as at least one induction coil. If the means for supplying energy can be controlled by an external device, the energy supply to the implant and thus the release of the active ingredient is advantageously enabled by targeted control, in particular by an external user. A particularly simple type of control is achieved by an electromagnetic field, which induces a current in an induction coil of the implant, with which current can be supplied to the microchip and all components connected to it.However, the use of other types of energy sources, such as a laser, infrared light, or magnets, is also in accordance with the invention.

[0013] In one embodiment of the invention, it is proposed that the means for inducing a temperature change comprise a resistive heating element, an overload protection circuit, a Peltier element, a Zener diode array, a matrix circuit of resistors, a matrix of a conductive polymer, and / or a passive resonant circuit system. An overload protection circuit, in particular, is a common component of microchips, particularly ASICs. The microchip would be supplied with power by the power supply means, with any excess power being dissipated by the overload protection circuit in the form of heat energy. A Zener diode array, a matrix circuit of resistors, and a matrix of a conductive polymer function similarly. A Peltier element, on the other hand, can also have a cooling effect. A passive resonant circuit system, on the other hand, heats up when a resonant frequency is reached.Within the scope of the invention, the passive oscillating circuit could be designed to be strongly detuned in the idle state compared to the operating frequency and, if necessary, a capacitor integrated on the ASIC could be switched on, which is dimensioned such that the resulting resonance frequency of the passive oscillating circuit lies in the range of the operating frequency in order to generate heat or cold in this way.

[0014] In a further development of the invention, it is proposed that the reservoir comprises a thermoresponsive material, in particular a thermoresponsive polymer or thermoresponsive nanoparticles, particularly preferably poly(N-isopropylacrylamide) or lipid-based nanoparticles, in particular being formed from one of the materials. Thermoresponsive materials generally have the advantage that they react to temperature changes with changes in their structure or a phase change and can thus be controlled by a temperature change. A reservoir generally absorbs active ingredients in its cavities, so that a change in the structure can lead to the cavities opening. At the same time, a return to the initial temperature leads to a further change in the structure and thus, advantageously, to the return of the structure of the closed cavities.Thermoresponsive polymers or nanoparticles have proven particularly advantageous because their composition can be varied and supplemented with copolymers to adjust the lower critical solution temperature, i.e., the temperature at which a phase transition of the polymer occurs and the encapsulated active ingredient is released. Specifically, poly(N-isopropylacrylamide)-based nanoparticles or lipid-based nanoparticles, such as liposomes and solid lipid nanoparticles (SLN), have proven particularly advantageous for drug delivery applications.

[0015] In an embodiment of the invention, it is proposed that the reservoir has a plurality of chambers, wherein in particular each chamber can be reversibly converted separately from the first state at the first temperature to the second state at the second temperature. According to the invention, a plurality of chambers is understood to mean both a reservoir with several adjacent chambers and several spatially separated chambers. It is particularly advantageous if these different chambers can be controlled separately from one another so that the desired dosage can be individually designed more precisely. Thus, it is also according to the invention that each of the chambers has a single dose, so that controlling a chamber leads to its complete emptying.In a further development of the invention, it is proposed that the reservoir be designed and arranged such that it covers the means for inducing a temperature change and, in particular, hermetically seals it. This advantageously ensures that the means for inducing a temperature change, which, as described above, can be electrical components, are protected, in particular, from liquids and other environmental influences. Sealing of the remaining microchip, on which the means for inducing a temperature change are located, by the reservoir is also provided according to the invention.

[0016] In one embodiment of the invention, it is proposed that the means for inducing a temperature change be doped, coated, and / or loaded with the active ingredient. In this case, the means for inducing a temperature change are particularly preferably designed as a single piece with the reservoir. Thus, a temperature change has a direct effect on the thermoresponsive structures without the need for a special thermal conductor or the like. In this case, the temperature change leads to a break in the connection between the active ingredient and the means for inducing a temperature change, thus releasing them. In this context, the invention may, for example, provide for loading the polymer with metal particles.

[0017] In a further development of the implant according to the invention, it is proposed that it comprise at least one sensor, in particular at least one IOD sensor and / or temperature sensor. Sensors can be used to monitor important environmental parameters, which are particularly relevant for deciding on the timing of the active ingredient release and the dosage of the active ingredient to be released. If an intraocular pressure-lowering active ingredient is to be released, it is certainly relevant to the decision whether and to what extent the intraocular pressure deviates from the norm. Furthermore, monitoring of the therapeutic success with the active ingredient used is possible. A temperature sensor serves in particular to monitor the means for inducing a temperature change and to check whether these are functioning as intended by a user when controlling them. The at least one sensor is also powered by the means for supplying power to the microchip.

[0018] Within the scope of the invention, however, embodiments are also possible in which the intraocular pressure measurement is performed by a separate implant. In these embodiments of the invention, the drug-releasing implant as such merely comprises at least one temperature sensor. However, in these embodiments, the signal characterizing the intraocular pressure is generated by a second implant designed separately from the drug-releasing implant.

[0019] In one embodiment of the invention, it is proposed that it comprise means for communication with an external device. Such means serve to transmit data to an external device so that, for example, data recorded by a sensor or data on the fill level of the reservoir can be sent to an external device and evaluated there by a user. Monitoring the parameters locally present on the implant is particularly advantageous for individual planning and adaptation of the patient's therapy. It is very advantageous for the means for communication to only be activated when there is an appropriate power supply so that the data can always be retrieved when needed. However, periodic transmission of the data is also in accordance with the invention so that operating errors do not affect the therapy.According to the invention, communication with an external device is particularly contactless, allowing reading of the implant even without removing it from the eye. For this purpose, the communication means, in one embodiment, are designed as an antenna that emits, in particular, electromagnetic waves that can be read by an external device. Advantageously, the communication means in this embodiment can also serve to transmit energy to the implant.

[0020] In a further development of the invention, it is proposed that the first temperature corresponds to the usual, average body temperature of the human eye and / or the second temperature corresponds to a temperature of > 38 °C, in particular a temperature between 39 °C and 42 °C. In the first state, the reservoir should thus store the active ingredient so that the active ingredient does not escape unintentionally at the average body temperature of the human eye. Rather, the intention is that the active ingredient can only escape from the reservoir upon deliberate activation, i.e. when the energy supply to the implant is started. For this purpose, the second temperature is selected in comparison to the first temperature such that the temperature difference enables reliable triggering of the release of the active ingredient and at the same time avoids unintentional triggering in the event of slight fluctuations in the eye temperature.At the same time, the second temperature, as the trigger temperature, should be as close as possible to the average temperature of the human eye to avoid discomfort for the patient or even damage to the eye. A temperature between 39 °C and 42 °C has proven particularly advantageous and meets the aforementioned criteria.

[0021] Furthermore, the object of the invention is achieved by a system for the controlled release of a therapeutic active ingredient, comprising an implant according to the aforementioned embodiments and means for controlling and / or reading the implant. The means for controlling and / or reading the implant serve to activate the implant, in particular the means for supplying energy, and / or to receive data emitted by the implant. If the implant has an induction coil as a means for supplying energy, as in one exemplary embodiment, the means for controlling the implant could generate an electromagnetic field, which induces a current in the induction coil of the implant. Other control means, such as a laser or NI R light, are also according to the invention.To read the implant, the means are designed in particular as transponders that are suitable for contactless data transmission, for example via Bluetooth, NFC, RFID, or other radio technology.

[0022] In an embodiment of the system, it is proposed that the means for controlling and / or reading the implant be a handheld reader, a reading unit integrated into glasses, or an adhesively attached reading unit, in particular one integrated into an eye patch. A smartphone is also inventive, at least as a means for reading the implant, with the data being received by the smartphone, for example, via Bluetooth, and being analyzable via an app. In particular, the handheld reader, but also the glasses, in contrast to the smartphone, are also suitable as a means for controlling the implant, since they can be brought close to the eye with the implant without any problems and, at the same time, offer the possibility of being supplemented by devices suitable for generating and emitting an electromagnetic field, laser, infrared light, or magnetic field.

[0023] In further development of the system, it is proposed that the system regularly prompts a user to

[0024] Intraocular pressure measurement and / or information on the dosage of the delivered active ingredient. Such a request is particularly important for ensuring the success of the therapy and calculating the actually required dosage. According to the invention, this request is sent via an app on the user's or patient's smartphone or, optionally, via the handheld reader, if the user uses this as a means of controlling and / or reading the implant. If the implant has an internal power supply, the signal can also originate from the implant.

[0025] Finally, the object of the invention is achieved by a method for the controlled release of a therapeutic active ingredient, in particular using an implant or a system according to the aforementioned embodiments, comprising the following steps: heating or cooling the means for inducing a temperature change; transferring the temperature change generated at the means for inducing a temperature change to the reservoir in order to convert the reservoir from a first state at a first temperature to a second state at a second temperature and to thermally trigger the release of the active ingredient held in the at least one reservoir;Terminating the release of the active ingredient stored in the at least one reservoir by transferring the reservoir from the second state at a second temperature to the first state at a first temperature; Cooling the reservoir by terminating the temperature change of the means for causing a temperature change according to the first method step;

[0026] In the first step of heating or cooling the means for inducing a temperature change, they are supplied with energy to be able to induce the temperature change. The exact function of the means for inducing a temperature change depends on their design, which, depending on the embodiment, can be an ohmic heating element, an overload protection circuit, a Peltier element, a Zener diode arrangement, a matrix circuit of resistors, a matrix of a conductive polymer and / or a passive oscillating circuit system. This temperature change is transferred to the reservoir. This transfer takes place particularly advantageously via heat conduction. Alternatively, the reservoir and the means for inducing a temperature change can be designed as a single piece or can be adjacent to one another, so that the temperature change is transferred through their material.The temperature change is selected such that it moves the reservoir from the first state, in which the reservoir stores the active ingredient, to the second state, in which the reservoir releases the active ingredient. Only when the amount or dosage of active ingredient, individually determined according to therapy requirements, has been released, is the energy supply to the microchip and thus to the means for inducing a temperature change stopped. This stops the temperature change and the reservoir returns to the first temperature, i.e. the local ambient temperature in the eye. This returns the reservoir to the first state and no longer releases the active ingredient stored in it. Accordingly, the reservoir can be reversibly transferred between the first and second states, meaning that the reservoir does not have to be completely emptied and the delivered dose of active ingredient can be controlled.The above steps can be repeated as needed until the reservoir is empty.

[0027] In one embodiment of the method, it is proposed that the means for inducing a temperature change are heated in the first method step due to an oversupply of energy to the microchip by the energy supply means. By oversupplying the microchip with power, the means for inducing a temperature change convert the excess power not consumed by the remaining components of the microchip, such as a sensor, into thermal energy. Commercially available microchips, particularly ASICs, usually contain an overload protection circuit to protect them from high electrical voltages and voltage spikes. This converts a targeted oversupply into thermal energy and thus induces a temperature change. Other circuits, such as a matrix of resistors, can also have the same effect and induce a temperature change in the event of an oversupply.This design proves particularly advantageous due to its simplicity. The competent expert will recognize that the implant also features a "real" protective circuit, which intervenes if the implant is oversupplied during operation without the intention of releasing active ingredient.

[0028] In a further development of the method, it is proposed that the amount of active ingredient released is controlled via the duration for which the reservoir is in the second state and / or the temperature difference between the first temperature and the second temperature, in particular via the means for controlling and / or reading the implant. If the reservoir is held in the second state for a longer period, the active ingredient continues to be released at the same rate over this longer period. However, if the temperature difference measured by sensors is greater, a greater amount of the active ingredient is released in the same time. Accordingly, a combination of a longer period in the second state and a greater temperature difference is also according to the invention.This influencing of the delivered amount of active ingredient is carried out in particular by a user or automatically by software via the means for controlling and / or reading the implant, so that the therapy can be individually and dynamically adapted to the patient's needs. In particular, an arrangement comprising a valve for in vivo modification of intraocular pressure according to German patent application DE 10 2019 126 959 A1 can be used in this context according to one of the patent claims 1 to 12 disclosed therein.

[0029] In one embodiment of the method, it is proposed that the amount of active ingredient to be released is calculated based on the intraocular pressure determined by the at least one sensor. Particularly in the case of glaucoma being treated, it is necessary to reduce the intraocular pressure as much as possible. For this purpose, intraocular pressure-lowering agents are used. In order to be able to appropriately regulate the extent of the reduction in intraocular pressure, it is therefore necessary to determine the intraocular pressure and release only as much active ingredient as is necessary to bring the elevated intraocular pressure closer to an ideal value. Particularly with constant or regular monitoring of the intraocular pressure, its determination allows for regular adjustment of the amount of active ingredient to be released. Accordingly, the therapy can be individually tailored to the patient's needs.

[0030] The invention is described by way of example in a preferred embodiment with reference to a drawing, wherein further advantageous details can be taken from the figures of the drawing.

[0031] Functionally identical parts are provided with the same reference symbols.

[0032] The figures in the drawing show in detail:

[0033] Fig. 1: Schematic representation of an implant according to the invention in a first embodiment. Fig. 2: Schematic representation of an implant according to the invention in a second embodiment.

[0034] Fig. 3: schematic representation of an inventive

[0035] System consisting of an implant and means for controlling and / or reading the implant.

[0036] Fig. 4: Schematic representation of the possible states of the

[0037] Reservoirs.

[0038] Fig. 1 shows a schematic representation of an implant 1 according to the invention in a first embodiment. The implant 1 has a design and size that allows insertion into a human eye without significantly restricting the patient. The implant 1 has a microchip 2 that ensures the basic functions of the implant 1. For this purpose, it is sufficient if the microchip 2 is designed as an ASIC. The microchip 2 receives the energy required for its functionality from the energy supply means 3, which in the illustrated embodiment is designed as an induction coil. The energy supply means 3 can be controlled by an external device that, 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 means 3 supply any sensors 7 and communication means 8 connected to the microchip 2, which are shown schematically here together. The sensors 7 are designed in particular to detect environmental parameters, wherein the communication means 8 enables both data transmission of the detected environmental parameters to an external device and control of the sensors 7 and the rest of the microchip 2 by an external device. The microchip 2 further comprises means 5 for inducing a temperature change, which are shown only schematically here. These can be, for example, Peltier elements or, for example, an overload protection circuit, which converts the current from the power supply means 3 via the microchip 2 into thermal energy.For this purpose, an oversupply of the implant 1 is deliberately enforced so that the electronic components of the microchip 2 and sensors 7 and means 8 for communication are supplied with sufficient power, while the remaining excess power is used by the means 5 for inducing a temperature change to generate a temperature change. The temperature of the reservoir 4 is measured by means of a temperature sensor 5a, not shown in the figure. This temperature change is transmitted to the reservoir 4, which is thermally connected to the means 5 for inducing a temperature change. Due to these temperature changes, the reservoir 4 is converted from a first state in which the reservoir 4 stores the active ingredient absorbed therein, to a second state in which the reservoir 4 releases the active ingredient.A certain basic release of active ingredient can also occur without the reservoir being heated, which can be therapeutically advantageous in certain applications. Fig. 2 shows a schematic representation of an implant 1 according to the invention in a second embodiment. In this embodiment, the reservoir 4 is split into a plurality of chambers 6, each of which holds a certain amount of the active ingredient. Each chamber 6 can be reversibly converted from the first state to the second state independently of one another, wherein the means 5 for inducing a temperature change are each thermally connected to the chambers 6. For this purpose, in the embodiment shown, both chambers 6 and means 5 for inducing a temperature change are spatially separated from one another, wherein each means 5 for inducing a temperature change is thermally connected to a respective chamber 6.This embodiment makes it possible to control the individual chambers 6 separately and to adapt the therapy more flexibly and individually to the patient's needs and therapy goals.

[0039] Fig. 3 shows a schematic representation of a system according to the invention comprising implant 1 and means 9 for controlling and / or reading the implant 1. The means 9 for controlling and / or reading the implant 1 communicate both with the means 3 for power supply and with the sensors 7 and the means 8 for communication. In this embodiment, the means 9 for controlling and / or reading the implant 1 emit an electromagnetic field, which induces a current in the means 3 for power supply in the form of an induction coil, thereby supplying the implant 1 with power. At the same time, when power is supplied, the sensors 7 detect environmental parameters, which are sent contactlessly via the means 8 for communication to the means 9 for controlling and / or reading the implant, in particular via Bluetooth, RFID, NFC, or other wireless technologies.

[0040] Fig. 4 shows a highly simplified schematic representation of the possible states of the reservoir 4. In a highly simplified manner, a first temperature Ti is assigned to a first state Zi, while a second temperature T2 is assigned to a second state Z2. In the first state Z1, the reservoir 4 stores the active ingredient absorbed therein, while in the second state Z2 it releases the active ingredient. The first temperature Ti corresponds approximately to the average eye temperature, while the second temperature T2 is a temperature that deviates from this, the degree of the deviation being within a range that avoids any impairment of the patient, but at the same time prevents undesired transitions of the reservoir 4 into the second state Z2 due to normal temperature fluctuations.The double arrow shown between the two states Z1 and Z2 symbolizes the reversibility of the transfer of reservoir 4 to the respective other state. Thus, the release of the active ingredient can be controlled independently of the size of reservoir 4, without the entire active ingredient contained in reservoir 4 having to be released in one dose. In practice, however, T1 represents an upper limit, whereas T2 defines a lower limit. States 1 and 2 are found in the ranges below and above, respectively.

[0041] LIST OF REFERENCE SYMBOLS

[0042] 1 implant

[0043] 2 microchips

[0044] 3 Means of energy supply 4 Reservoir

[0045] 5 Means of causing a change in temperature

[0046] 5a Temperature sensor

[0047] 6 combs

[0048] 7 Sensor 8 Means of communication

[0049] 9 Means for controlling and / or reading the implant

[0050] Zi First State

[0051] Z2 Second state

[0052] Ti First temperature T2 Second temperature

Claims

PATENT CLAIMS 1. Implant (1) comprising a microchip (2), means (3) connected to the microchip (2) for supplying energy to the microchip (2), and a reservoir (4) suitable for storing and repeatedly releasing an active ingredient, the microchip (2) comprising means (5) for inducing a temperature change which are thermally connected to the reservoir (4), characterized in that the reservoir is reversibly convertible from a first state (Zi) at a first temperature (Ti) to a second state (Z2) at a second temperature (T2), the reservoir (4) storing the active ingredient in the first state (Z1) and releasing the active ingredient in the second state (Z2).

2. Implant (1) according to claim 1, characterized in that the means (3) for supplying energy to the microchip (2) can be controlled by an external device and are designed in particular as at least one induction coil.

3. Implant (1) according to claim 1 or 2, characterized in that the means (5) for causing a temperature change comprise an ohmic heating element, an overload protection circuit, a Peltier element, a Z-diode arrangement, a matrix circuit of resistors, a matrix of a conductive polymer and / or a passive resonant circuit system.

4. Implant (1) according to claim 1, 2 or 3, characterized in that the reservoir (4) comprises a thermoresponsive material, in particular thermoresponsive polymer or thermoresponsive nanoparticles, particularly preferably poly(N-isopropylacrylamide) or lipid-based nanoparticles, in particular is formed from one of the materials.

5. Implant (1) according to one of the preceding claims, characterized in that the reservoir (4) has a plurality of chambers (6), wherein in particular each chamber (6) is individually reversibly convertible from the first state (Zi) at the first temperature (Ti) to the second state (Z2) at the second temperature (T2).

6. Implant (1) according to one of the preceding claims, characterized in that the reservoir (4) is designed and arranged such that it covers the means (5) for causing a temperature change and in particular hermetically seals it.

7. Implant (1) according to one of the preceding claims, characterized in that the means (5) for causing a temperature change are doped, coated or loaded with the active ingredient.

8. Implant (1) according to one of the preceding claims, characterized in that it has at least one sensor (7), in particular at least one IOD sensor and / or temperature sensor.

9. Implant (1) according to one of the preceding claims, characterized in that it comprises means (8) for communication with an external device.

10. Implant (1) according to one of the preceding claims, characterized in that the first temperature (Ti) corresponds to the usual, average body temperature in the human eye and / or the second temperature (T2) to a temperature of > 38 °C, in particular a temperature between 39 °C and 42 °C.

11. System for the controlled release of a therapeutic agent, comprising an implant (1) according to one of claims 1 to 10 and means (9) for controlling and / or reading the implant (1).

12. System according to claim 11, characterized in that the means (9) for controlling and / or reading the implant (1) is a handheld reader, a reading unit integrated in a pair of glasses or an adhesively attached reading unit, in particular a reading unit integrated in an eye patch.

13. System according to claim 11 or 12, characterized in that it sends a user a regular request for intraocular pressure measurement and / or information on the dosage of the delivered active ingredient.

14. A method for the controlled release of a therapeutic agent, in particular using an implant (1) according to one of claims 1 to 10 or a system according to one of claims 11 to 13, comprising the following steps: a) heating or cooling the means (5) for causing a temperature change, b) transferring the temperature change generated at the means (5) for causing a temperature change to the reservoir (4) in order to transfer the reservoir from a first state (Zi) at a first temperature (Ti) to a second state (Z2) at a second temperature (T2) and to release the agent contained in the at least to thermally trigger an active substance stored in a reservoir (4), c) terminating the release of the active substance stored in the at least one reservoir (4) by transferring the reservoir from the second state (Z2) at a second temperature (T2) to the first state (Z1) at a first temperature (Ti) cooling the reservoir by terminating the temperature change of the means (5) for causing a temperature change according to step a).

15. The method according to claim 14, characterized in that the means (5) for causing a temperature change in step a) are heated due to an oversupply of the microchip (2) with energy by the means (3) for supplying energy.

16. Method according to claim 14 or 15, characterized in that the amount of active substance released is controlled via the duration of bringing the reservoir (4) into the second state (Z2) and / or the temperature difference between the first temperature (Ti) and the second temperature (T2), in particular via the means (9) for controlling and / or reading the implant (1). 1 / .Method according to claim 14, 15 or 16, characterized in that the amount of active substance to be released is calculated on the basis of the intraocular pressure determined by the at least one sensor (7).

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