EP4192555A1

EP4192555A1 - Nasal applicator

Info

Publication number: EP4192555A1
Application number: EP21755988.9A
Authority: EP
Inventors: Klaus Sinner; Francois Henri Mathieu Marie Souren
Original assignee: Hatchmore Labs GmbH
Current assignee: Hatchmore Labs GmbH
Priority date: 2020-08-10
Filing date: 2021-08-09
Publication date: 2023-06-14
Also published as: WO2022034036A1; US20240024594A1; JP2023537092A

Abstract

The present invention relates to a nasal applicator (100) for administering nasally at least one medical substance (S), in particular an analgesic, having a housing (2), comprising or connected to: a substance reservoir (R) for holding a quantity of the substance (S); a call-down device (1) for actuation by the user with the aim of calling down a next application dose (D_n) of the substance (S); a dispenser (3) for dispensing application doses (D₀, D₁, D₂,..., D_n-1, D_n, D_n+1,...) in response to an actuation of the call-down device (1) at a respective dispensing time (tA₀, tA₁, tA₂,..., tA_n-1, tA_n, tA_n+1,...); a connection point (4a) for a nose attachment (4), or a nose attachment (4) or a nose piece; and a delivery device (17) for delivering an application dose of the substance (S) via the connection point (4a) or the nose attachment (4) or the nose piece and/or from the nasal applicator (100).

Description

The present invention relates to a drug delivery device, in particular a nasal applicator, according to claim 1. It also relates to a system according to claim 36. Nose applicators are known from practice, by means of which a patient can apply a drug or an active substance nasally. It is the object of the present invention to propose a further nasal applicator. The object of the invention is achieved by the nasal applicator having the features of claim 1, further by the system having the features of claim 36. According to the invention, a drug delivery device (for nasal, inhalative, intravenous, oral, buccal, sublingual, etc. delivery), in particular a nasal applicator for administration or nasal administration of at least one substance, e.g. a medicinal or non-medicinal substance, e.g. B. a medicinal or non-medicinal active ingredient proposed. The medicinal substance can in particular be an analgesic. For this purpose, the drug delivery device or the nasal applicator has a housing. The medication delivery device has or is connected to a substance reservoir for holding a quantity of the substance. The medication delivery device is connected to or includes a retrieval device for actuation by the user/patient. The retrieval device is programmed or otherwise prepared so that the user of the drug delivery device can retrieve a next application dose of the substance by actuating the retrieval device. The purpose or aim of the retrieval device is therefore to be able to trigger an application dose. The medication delivery device further includes or is connected to a delivery meter. The dispensing dispenser is provided for dispensing application doses upon actuation of the retrieval device. The delivery takes place, if it takes place, at a so-called delivery time. The medication delivery device also has a connection point for a nose attachment or a nose piece or is connected to a nose attachment or a nose piece. Finally, the medication dispensing device has or is connected to a dispensing device for actively dispensing an application dose of the substance via the connection point or the nasal attachment or the nose piece and/or out of the nasal applicator. The system according to the invention comprises one or more nasal applicators according to the invention and one or more peripheral devices, one or more of the nasal applicators being in signal or communication connection with one or more of the peripheral devices, in particular by means of its control device, or being prepared or programmed for this purpose. When reference is made herein to a user, this includes the patient who is self-medicating, the caregiver, the doctor, the patient's relatives and more, e.g. B. at the behest of the patient, the medication delivery device as described herein is used in the medication of the patient. In all of the above and following statements, the use of the expression “can be” or “can have” etc. is to be understood synonymously with “is preferably” or “has preferably” etc. and is intended to explain an embodiment according to the invention. Whenever numerical words are mentioned herein, the person skilled in the art understands them as indicating a numerical lower limit. Provided that this does not lead to a discernible contradiction for the person skilled in the art, the person skilled in the art always reads “at least one” or “at least one” when specifying “a” or “an”. This understanding is also encompassed by the present invention, as is the interpretation that a numerical word such as "a" can alternatively be meant as "exactly one" wherever this is clearly technically possible for a person skilled in the art. Both are encompassed by the present invention and apply to all numerals used herein. Where "programmed," "provided," or "configured" is used herein, it is also disclosed to interchange these terms. When reference is made herein to "programmed," "designated," or "configured" to perform a step or action, it is also disclosed that that step or action is optionally performed automatically, e.g. B. from the control device. Advantageous further developments of the present invention are the subject matter of subclaims and embodiments. Whenever an embodiment is referred to herein, it represents an exemplary embodiment of the invention expressly does not have this or these features in other embodiments that are also according to the invention, e.g. B. in the sense of a disclaimer. For each embodiment mentioned herein, the contrary embodiment, for example formulated as a negation, is also disclosed. Embodiments according to the invention can have one or more of the features mentioned above and/or below in any technically possible combination. Whenever a suitability, purpose, step or method step is recited herein, the present invention also encompasses corresponding programming or configuration of an apparatus or portion thereof suitable for achieving or carrying out. Even if the present invention is not limited to a nasal applicator, but rather relates to drug delivery devices as such, the focus in the following is on nasal applicators. The teachings, explanations, and advantages made of the nasal applicator apply without prejudice to drug delivery devices, and vice versa. In some embodiments, the terms "drug delivery device" and "nasal applicator" may be synonymous. In some embodiments, these terms are interchangeable. Thus, what is stated herein for the “medication delivery device” also applies to the “nasal applicator”, and vice versa. The applicator can optionally be used for various forms of application, e.g. B. can be used sublingually, inhalatively and even intravenously. The connection point disclosed herein can be designed to be connected to a wide variety of ports through which a liquid can be conveyed, such as. B an impaction baffle or step baffle or impaction baffle, which breaks up the liquid into small droplets, a two-jet atomizer (impinging jet), a porous membrane, a perforated plate (Rayleigh breakup principle), an infusion tube, a vortex chamber, nasal cannula, other nose adapters for generating small droplets, etc. It may be connected to any of these. In some embodiments, the nasal applicator also has a dosing chamber. The dosing chamber serves to temporarily receive the application dose of the substance held in the substance reservoir. In some embodiments, the nasal applicator additionally has a loading device for loading the dosing chamber with the application dose of the substance from the substance reservoir. In some embodiments, the pick and place device is a pump. In some embodiments, the loading device is a membrane that allows liquid to diffuse into the metering chamber over time. In other embodiments, the loading device is a dropper, alternatively a bellows, a bellows or a cuff, a bolus system, or the like. In some embodiments, the concentration itself can be mixed to simulate different dosages. In other words: Different mixtures of carrier liquid and active ingredient are provided in a dosing chamber of constant and/or variable size (e.g. 100 µL) in order to achieve the desired concentration, e.g. 50 µg/100 µL or 60 µg/100 µL, etc. For this purpose, and optionally additionally or alternatively for other purposes, a second fluid chamber can be provided in addition to the substance reservoir, which has a second fluid (preferably a liquid) which differs from the substance of the reservoir or is intended to hold it, for example a Fluid for diluting the substance with the aim of setting a desired concentration. A pump, or further pump, for discharging the second fluid from the second fluid chamber can, like any other pick-and-place device such. B. a syringe may be provided. The second fluid chamber, or a further, third, can have a desiccant or be provided for this purpose. Instead of or in addition to the desiccant, an antidote for the or an active ingredient of the substance can be provided, a neutralizing agent in order to reduce or block the pharmacological effect. In some embodiments, the dispensing device is arranged for, in particular active, dispensing of the application dose of the substance present in the dosing chamber via the connection point, the nasal attachment or the nose piece and/or out of the nasal applicator. In some embodiments, in a motor-driven direct piston drive, i.e. in a system in which the vortex chamber is coupled directly to a syringe and/or cylinder ampoule syringe (carpule), which acts as a reservoir and dosing chamber here—e.g. B. by means of a Motor or otherwise - the required triggering speed, force and/or pressure can be generated by applying pressure to the pressure plate of the syringe. The delivery quantity can be determined and controlled using a flow sensor. The flow sensor is provided to stop the movement of the dispensing device in these embodiments, for example to stop the optional motor when the desired dispensing amount has been reached. In some embodiments, an audio signal can optionally be emitted while and/or while a fluid is being applied. Alternatively or additionally, in some embodiments, an audio signal can be given after application is complete. Different tone signals as well as different tone types and pitches are encompassed by the present invention. In some embodiments, dose setting and/or initiation is manual, or a combination of manual and automatic. In some embodiments, the dispensing device and/or the equipping device has an energy store for mechanical or electrical energy or spring energy. In certain embodiments, the dispensing device and/or the equipping device has an energy store for hydraulic and/or pneumatic energy. In some embodiments, the stored energy is energy generated by the human body or gravity. In these embodiments, the energy is stored by changing the density or by converting this energy into another form of energy. In some embodiments, the dispensing device and/or the equipping device have a motor, preferably an electric motor. In some embodiments, the motor may also be powered by compressed air (pneumatic, hydraulic) or by mechanical energy, such as spring energy and/or human energy. The motor can also be a pump. In some embodiments, the dispensing device and/or the equipping device has a spindle. The spindle can be driven electrically, pneumatically, hydraulically, mechanically or by means of spring energy. The spindle can be designed in different ways, e.g. B. as a linear system (linear axis) with toothed belt and spindle drive for a linear movement, as ball bushings, as a threaded spindle (ball screw or trapezoidal thread gear), as a shaft guide, as a grooved shaft, as a cylindrical, flanged, rotary, short-stroke, long-stroke -Torque ball bushings for torque transmission, as torque shafts with and without a groove, as rail guides, as electric, pneumatic or hydraulic cylinders, as telescopic cylinders (e.g. multi-stage hydraulic piston) or as a single or double-acting cylinder. The spindle can be smooth in some embodiments and z. B. be driven by two pairs of obliquely mounted and opposite ball bearings. A rolling ring gear (Uhing gear) can be provided. In certain embodiments, the nasal applicator has no spring element and/or no store for mechanical energy or spring energy. In certain embodiments, the equipping device and/or the dispensing device has no spring element and/or no store for mechanical energy or spring energy. In some embodiments, the motor is connected to the spindle. In these embodiments, the motor is directly connected to the spindle. Alternatively, motor and spindle are connected indirectly, i. H. a translation or reduction can be interposed. Motor and spindle can be referred to together as a gearbox. It may be a fixed gear in some embodiments, i. H. Speed ratio and torque conversion are not changeable. In other embodiments, the transmission can be an adjustment transmission (stepped and/or stepless). In further embodiments, the transmission can be a manual transmission for speed and/or torque gradation and/or reversal of direction of rotation. Within the transmission, the step-up or step-down can be positive or non-positive, e.g. B. in a gear and / or friction gear and / or epicyclic gear (all three gears), a chain and / or belt drive (both traction gear), a planetary gear, a pressure medium gear (e.g. as in the hydraulic gear of a car brake), a linkage (e.g. as in the crank mechanism of an internal combustion engine - crankshaft and connecting rod), a cam gear (e.g. as in the cam gear of a valve control system), a screw and worm gear (e.g. as in a vice or jack), a linear chain drive, a roller body drive, a power split drive (e.g. a differential drive), a multi-plate chain drive, a rolling ring drive, a coupling drive (e.g. crank drive, Maltese cross drive) or a drive with an elastic transmission element (e.g. sliding key gear). In some embodiments, the nasal applicator also has a mechanism for changing the capacity of the metering chamber for the application dose of the substance. The capacity can be changed manually or automatically. Such a change in the capacity can take place by changing the stroke of the equipping or dispensing device. Examples of this are: Lengthening/shortening the travel path of the loading or unloading device, rotation of an inclined plane, by means of a curve e.g. B. a cam, groove, heart curve, etc., an adjustable end stop/stop, adjustable pins as travel limiters, a change in the dosing chamber diameter, a change in the loading or dispensing device geometry (e.g. round to oval), a change in the dosing chamber geometry (e.g. round to oval) and/or telescopic pistons running outwards or inwards. In some embodiments, it can be provided to change the capacity of the dosing chamber by first moving the piston by rotating the spindle in a first direction (approximately counterclockwise) and enlarging the dosing chamber accordingly in order to suck substance from the reservoir . The spindle is then rotated in the opposite direction to dispense the application dose thus introduced into the dosing chamber. In certain embodiments, it can be provided that the dosing chamber is filled and emptied by means of a sliding crank drive. The slider crank drive can have or consist of an eccentric shaft and a push rod which can be rotated on or on the eccentric shaft relative to the latter. The slider crank drive is used to transform a rotary movement into an oscillating pushing movement, or vice versa. In relation to the configuration of the equipping or dispensing device that is relevant here, this can result in a piston motor with a piston that moves back and forth in a straight line in the cylinder. The control device can be programmed to both fill the dosing chamber by rotating the motor drive in a first direction and also to empty it again by rotating the motor drive in the same direction with the aim of dispensing the next application dose. The quantity of the dose applied here can be fixed by turning it by a corresponding angular value. Alternatively, the control device can be programmed to fill the dosing chamber by turning the motor drive in a first direction and to empty it again by turning the motor drive in the second direction opposite to the first, with the aim of dispensing the next application dose. The quantity of the dose applied in this way can in turn be fixed by rotating it by a corresponding angular value, which makes the setting of the dose variable. The sliding crank drive can be used to advantage here. In some embodiments, a reduction in the size of the metering chamber is encompassed by the present invention by not changing the stroke of the deployment mechanism but by moving the linkage side. Does the dosing chamber z. B. a maximum volume of 150 µL, the following procedure can be offered, for which the control device can also be programmed: The dosing chamber is filled with 150 µL with the intake stroke, i.e. it is completely filled. The application dose to be delivered is z. B. but only 50 µL which by reversing the path z. B. the piston travels back, is given what the discharge stroke. In this example, the remaining quantity in the dosing chamber is 100 µL. If the next application dose is 75 µL, for example, the device does not have to carry out a suction stroke, but does the delivery stroke straight away. The residual amount that remains in the dosing chamber after this last application is 25 µL. If the subsequent application dose z. B. 100 µL, this again requires a suction stroke of 75 µL. Alternatively, however, the dosing chamber can be refilled to 150 µL. Further alternatively, the present invention includes that a constantly large dosing chamber (e.g. 150 μL) is always only filled with the desired application volume (e.g. by means of a micropump, for example with 100 μL. In these embodiments, the triggering device is moved in the direction Joint moves to compress air first. Above a predetermined pressure, the valve opens and the air is forced through the vortex chamber together with the liquid. Alternatively, the compressed air is discharged via a vent valve. In some embodiments, the mechanism for changing the volumetric capacity is the Dosing chamber for the application dose of the substance Part of the dispensing dispenser Where a motor is referred to herein, it may be a Wankel motor In some embodiments, the nasal applicator further comprises an electronic control device. In some embodiments, the electronic control device is programmed to move the dispensing device at a variety of speeds, forces, pressures, accelerations and/or flow rates and/or to dispense substance at a variety of speeds, forces, pressures, accelerations and/or flow rates permit. Provision can thus be made, for example, to deploy at a first, in particular predetermined, speed, to deploy at a second, in particular predetermined, speed which differs from the first speed, and optionally at even further speeds. These rates of application can be defined as a function of the quantity to be applied and/or the volume of substance to be applied and/or its nature. In some embodiments, the nasal applicator has a second fluid chamber containing a desiccant or a means for neutralizing the substance. In some embodiments, the dispensing device and the equipping device have identical components or consist of them. In some embodiments, the electronic controller is programmed to act on the mechanism to vary the volumetric capacity of the metering chamber. In some embodiments, the equipping device for equipping the dosing chamber with the application dose of the substance has at least a first one-way valve or check valve and/or the Metering chamber is defined by at least a first one-way valve or check valve. In some embodiments, the pick-and-place device optionally has at least one valve which opens at a predetermined pressure value (e.g. 4 bar). In other words, the dosing chamber is pressurized by the dispensing device, as soon as it moves, the pressure in the dosing chamber rises to the predetermined pressure value (e.g. 4 bar), the valve opens and remains open until the dosing chamber is empty . Thus, the one-way valve can also have the function of a pressure sequence valve. Alternatively or additionally, a valve can be opened or closed by means of a pressure switch sensor or pressure sensor. This solution covers both the function of a non-return valve and the function of a pressure sequence valve (alternatively: pressure switching valve, pressure sequence valve or sequence valve) of another valve, a throttle, a lock for volume flow, etc. In some embodiments, the valve can be switched mechanically, in others electrically or electromagnetically, in still others pneumatically or hydraulically. A mechanically switchable valve is, for example, a check valve with a spring element. Further embodiments of a mechanically switched valve are, for example, a disk or ball check valve, a check valve or a backflow valve. In some embodiments, the valve is a switchable three-way valve. This can also be switched mechanically, electrically or electromagnetically, pneumatically or hydraulically. In some embodiments, the one-way valve is integrated or partially integrated in the triggering or equipping device. In some embodiments, the one-way valve is replaced by blocking the plug in the substance reservoir after the metering chamber is filled. The one-way valve can be integrated into the vortex chamber, ie z. e.g. beyond the junction, or in the nosepiece, etc. The vortex chamber may be shaped to function as a valve. The vortex chamber can have such a valve or be delimited by it on one side or defined in its extension. In some embodiments, the equipping device for equipping the dosing chamber with the application dose of the substance has at least one second valve, e.g. B. any as discussed herein or other valve, in particular a one-way valve or check valve. Alternatively or additionally, the dosing chamber is provided with at least one such, e.g. B. a second one-way valve or check valve limited. The second check valve preferably has an opening direction that is opposite to that of the first check valve in relation to the dosing chamber. In certain embodiments, the function of the first valve and the function of the second valve can be provided together in one component. In some embodiments, the nasal applicator also has a blocking device for temporarily blocking the delivery doser during a blocking period that begins again at or after the respective delivery time of the delivered application dose. The blocking period has a blocking period start and a blocking period end. In some embodiments, the nasal applicator also has a dose detection device for detecting the amount of the application dose delivered by means of the delivery doser at the time of delivery. In some embodiments, the nasal applicator also has a data memory for storing at least the dispensing times of one or more application doses that have already been dispensed. Alternatively or additionally, the heights of these application doses are also stored. In certain embodiments, the dosing chamber has or consists of a chamber for receiving the substance or the dosed amount of the substance. In these embodiments, the dosing chamber is in particular of variable size or variable capacity. In other embodiments, the dosing chamber is of non-variable size and/or always has the same capacity. In certain embodiments, the delivery meter is configured and arranged to deliver the amount of substance to be delivered as a spray and/or atomized. In certain embodiments, the nose applicator has no energy store and/or no means for delivering a predetermined, in particular mechanical, amount of energy to the energy store. In certain embodiments, the nasal applicator has no means for releasing the predetermined amount of energy from the energy store to the dosing chamber in order to subject the liquid therein to a predetermined pressure rise from a low pressure to a higher pressure and to initiate dispensing of the liquid from the dosing chamber. In some embodiments, the drug delivery device may further be connected to or include a locking device. In some embodiments, the blocking device is configured to temporarily block the dispensing doser during a blocking period, in particular a predefined blocking period. The blocking period begins, for example, after delivery of one, some or every application dose. Provision can thus be made for a blocking period to begin again at or after the respective delivery time of the delivered administration dose. The blocking period is defined by the start and end of the blocking period. Of the Blocking device scheduled blocking periods can have different durations or each have the same duration. Also, in some embodiments, the drug delivery device includes or is connected to a dose detection device. The dose detection device is programmed to detect the amount (e.g. as an amount, in weight units, in volume units, in material units such as moles, etc.) of the application dose that is delivered by means of the delivery dispenser at the respective delivery time. It can also be programmed to record the level of an application dose referred to herein as the initial dose. Furthermore, in some embodiments, the drug delivery device is connected to or includes an electronic controller. The drug delivery device may include or be connected to data storage for storage. He can at least the delivery times of one or more already delivered application doses, which z. B. before the next delivery time or in the past and / or store and / or have the heights of these application doses. The drug delivery device may include, or be connected to, a sensing device that is programmed to sense operation of the retrieval device by the user. The detection device can at least one operation of the retrieval device carried out or occurring at an operation time by the Record users as confirmation behavior and is preferably configured, programmed and/or provided accordingly. The aim of the actuation behavior is to trigger, deliver or have a next or future application dose applied and/or to check the circumstances for this, for example whether a previous delivery time was already a sufficiently long time ago. The actuation behavior can be the actuation of the retrieval device or can be detected from this by evaluation. The electronic control device can be programmed to read data stored in the data memory. It is also programmed to evaluate the user's actuation behavior that was detected by the detection device. In some embodiments, the result of the evaluation of the activation behavior of the user by means of the electronic control device can influence the predetermination of the amount of the next or future application dose. The electronic control device can be programmed to determine the time that has elapsed since the delivery time of one or more application doses that have already been delivered until the retrieval device is actuated, and to take it into account, above all quantitatively, in the predetermination. The electronic control device can be programmed to determine the time that has elapsed since the delivery time of one or more of the application doses that have already been delivered until the retrieval device is actuated and, above all quantitatively, to be taken into account when predetermining, at a predetermination point in time, the amount of the next or further application dose that the user should apply in the event that the user activates the retrieval device outside of a blocking period that may still last when the retrieval device is actuated can be delivered at a next delivery time. In some embodiments, the nasal applicator and/or one or more devices thereof are already programmed to predetermine the amount of the next or the further application dose at a predetermination time, which is during a blocking period. In some embodiments, the nasal applicator and/or its devices are not programmed so that the user can enter a period of time or a point in time after which the effect or a predetermined effect of the administered amount of active substance should be ended, degraded or fallen short of. In some embodiments, the nasal applicator and/or its devices are not programmed to compensate or change the predetermined height of the next or further application dose by means of a stored and/or retrieved height compensation factor. In some embodiments, the nasal applicator is not designed or configured to vaporize or vaporize an application dose. In some embodiments, the substance in the reservoir is continuously pressurized, such as by a spring arranged to compress the interior volume of the reservoir. The dosing chamber can be designed to, when it is loaded with the next or further application dose to be dispensed, into the volume required to hold this dose by means of a corresponding movement, e.g. B. the motor, the spindle and / or the placement device. It can then be reduced to deliver the dose. In some embodiments, the dosing chamber has a variable size or a variable capacity. This/this is preferably set automatically before or when it is loaded with the next or further dose by means of a motor, spindle and/or loading device. In some embodiments, the control device is programmed to initially increase the volume of the dosing chamber for filling it and then reduce it again for emptying it by means of a motor, spindle and/or loading device. For this purpose, the motor and/or spindle preferably rotate both in a first direction and later in a second direction opposite to the first. In some embodiments, the dosing chamber is delimited by inner wall sections of a piston, a movable plunger and/or by two valves. In some embodiments, the dosing chamber is formed thereby. In some embodiments, one or more of the valves defining the metering chamber are check valves or other mechanically operated valves. In some embodiments, the valves that define the metering chamber are stationary, which can increase their precision. Stationary means here that they are not connected to z. B. the movement of the piston can be moved. In certain embodiments, the valves defining the metering chamber are located at or associated with a common end of the metering chamber, e.g. B. both in an upper area, or both associated with the nosepiece. In some embodiments, the control device is programmed to move the placement device after actuation of the retrieval device with the aim of administering the next or further application dose both in a first direction and then in a second direction opposite to the first direction. In some embodiments, the nasal applicator does not have a piston pump. In some embodiments, the nasal applicator has no device for limiting the maximum possible stroke of a piston pump. In some embodiments, the nasal applicator does not include an electrical valve actuator. Next, it can be programmed to, e.g. B. during use of the nasal applicator and / or preferably without the intervention of a medical force, the manufacturer or other people, at a predetermination time (or determination time), preferably from a variety of possible heights - which are optionally not yet known before the start of treatment, e.g. B. at least within predetermined limits, variable - height of the next application dose, z. B. from a variety of possible or specifiable application doses, to predetermine or to determine, to select about, to calculate or to determine which next, z. B. at a next delivery time, can be delivered to the user or can be delivered for a delivery to this user, should this outside of a blocking period, if such is set, actuate the retrieval device. The level of the next application dose may be unknown in advance. The level of the next application dose cannot be stored in advance, that is to say cannot be taken from a memory; rather, it must be determined or predetermined. In some embodiments, the level of the next application dose is unknown before the control device has predetermined or determined it, for example by calculating it. It can thus be unknown up to the time of the predetermination. It can be variable. The electronic control device can be programmed to predetermine the level of the next application dose only after the retrieval device has been previously actuated. The electronic control device can be programmed not to predetermine the amount of the next application dose before the retrieval device is actuated at least for the first time. The electronic control device can be programmed to determine the amount of the next application dose for each application dose, or at least for several application doses. The electronic control device can be programmed to store the heights of dispensed application doses detected by means of the dosing detection device in the data memory. Such a predetermination time is at or after the actuation time. The step of predetermining takes place taking into account data read from the data memory. The data read out preferably include at least the delivery time of one or more of the application doses already delivered, or the time elapsed between the one or more delivery times of the application doses already delivered and the delivery time before or after the next actuation time. As an alternative or in addition, the data read out preferably include the level of one or more of the application doses that have already been dispensed, in particular by means of the medication dispensing device. In some embodiments, the level of the next application dose differs from the level of at least one, several or all previously predetermined application doses. In certain embodiments, the read-out data does not include any data that is entered based on an input from the patient with a view to his or her condition are not exclusively based on these, at best also. Such data can be patient-specific control data and/or data that depicts the duration, severity and/or frequency of complaints. In some embodiments, the dispensing dose is not the dose sensing device. As the dispensing doser dispenses the application dose to the patient, the dose sensing device records the amount of what has actually been dispensed. In some embodiments, the dosage detection device does not determine the level of the next application dose. In some embodiments, the nasal applicator does not have a display that would be controlled in order to display a remaining number of application doses and/or a number of application doses that have already been dispensed. In some embodiments, the nasal applicator does not have a large number of vials, in particular identical vials. In some embodiments, after a predetermined maximum amount of time has elapsed, no reminder signal, e.g. B. addressed to the user to operate the retrieval device again. In some embodiments, the data store also includes pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data, in particular relating to the substance that is or is to be administered. This data can be models, in particular PK models, or PK curves or include. This data can be formulas and/or generated based on them, e.g. B. on-line, by the electronic control device and / or in real time (real time), or generated. They may have been recorded or compiled individually for each patient. Alternatively or additionally, other data assigned to the substance can also be included in the data store or stored there. The data can include, for example, the dose half-life and/or the elimination or terminal half-life of the substance. The dose half-life is the time required for the concentration (e.g. in plasma, in blood, at the site of action (CNS, central nervous system), in adipose tissue, in the liver, etc.) to reach half the value (50%) of the administered dose is reduced. The elimination or terminal half-life is the time required for the concentration present at pseudo-equilibrium to fall by half (50%). The electronic control device is optionally programmed to also read out such data from the data memory. Furthermore, the next or further application dose of the substance is pre-determined in this case, also taking into account the additionally read out data. The predetermination time, as well as the actuation time, can optionally be the delivery time of the next correspond to the application dose, but it can also be before the delivery time. The end of the lockout period can be the time of maximum concentration (this time is also referred to herein as: t_Max) between delivery of two consecutive application doses of the substance or be derived from it. In certain embodiments, the blocking period can depend on the maximum concentration and accordingly on the doctor or other authorized persons or automatically on the medication delivery device, alternatively on a defined concentration, alternatively on the time until this defined concentration is undershot. In some embodiments, the electronic control device is further programmed to cause the next or the further application dose to be dispensed at the predetermined level at the corresponding dispensing time by means of the dispensing dispenser. The electronic control device is also programmed to subsequently store or have stored in the data memory the level and/or a resulting concentration of the application dose, for example as quantity information or volume information etc. of the substance, of the next application dose delivered. Furthermore, the control device is preferably programmed in order, for example at the same time as or subsequent to the dispensing of the application dose, to cause the blocking device to temporarily block the dispensing dispenser for a specific blocking period. The blocking period begins, for example, from or after the delivery time of this next application dose and is defined by a blocking period start and/or a blocking period end, which can also apply to any other blocking periods mentioned herein. The delivery time of the next application dose delivered can be stored in the data memory, and the control device can be programmed for this. In some embodiments, the electronic control device is further programmed to execute or initiate the sequence of the other steps mentioned above also in connection with one or more of the dispensing of further application doses following the next application dose, which are chronologically after the next application dose. In some embodiments, the electronic control device is programmed to read out data from the data memory which z. B. include PK curves and / or PK models, and which depict a time course of the concentration of the substance in the body, in particular in the blood of the patient. Based on these curves or models, the electronic controller can calculate a next maximum concentration. The next maximum may be the maximum that the concentration has between immediately consecutive dispensing times. It may be the result of accumulated application doses. In certain embodiments, this maximum concentration is calculated and used to determine the blocking period. When setting the blocking period, the The point in time at which this maximum is achieved must be taken into account. In some embodiments, the electronic control device is further programmed to determine the next application dose in such a way that the next maximum concentration will not exceed a predetermined maximum value or a predetermined maximum. In these embodiments, the application dose is determined on the basis of data stored in the data store, in particular PK curves or models, and a therapeutic maximum stored in the data store. The therapeutic maximum can be the maximum of a single application dose or the maximum of a sum of several applications or the maximum of a sum of several applications over a specific time or within a specific time interval. In some embodiments, the evaluation of the recorded activation behavior of the user includes determining the activation time at which the user would like to call up the next or the further application dose. Alternatively, the evaluation of the usage behavior includes the period of time that lies between this actuation time and the end of the blocking period of the last elapsed blocking period. In this case, the predetermination includes taking into account the determined next actuation time or taking into account the determined period of time. In some embodiments, the drug delivery device or nasal applicator further includes a feedback device. It serves the user, a feedback e.g. B. to his well-being, his pain condition or the like. The feedback device, which can be a switch, a touch surface, etc., can e.g. B. be provided to be operated by the user when, or as long as he is painless or can make a statement about the effect of the substance in his body in any other way. So it can be agreed that the user presses the feedback device for the first time, e.g. B. presses when the pain is first felt to be tolerable after the last application dose applied to the user. It can also be agreed that the user no longer actuates the feedback device from the point in time at which he feels pain again for the first time (due to the decreasing concentration of the substance in the body). The feedback device can be identical to the retrieval device, e.g. B. with its own switch evaluation, for example by being operated longer, shorter, more often or in some other way than the retrieval device, alternatively it can be a separate device for operation by the user. In this case, the detection device is programmed to detect that the feedback device has been actuated by the user at least at one, preferably a first, feedback point in time. Furthermore, the control device is programmed to determine the concentration of the substance present in the body or in the blood of the user at the at least one feedback point in time. A determination here can always be a calculation, reading out and/or reading. In addition, the control device is programmed to set a target concentration or its maximum value to a value below, above or equal to the determined concentration. Whenever a "target concentration" is referred to herein, it can be that concentration which produces a desired therapeutic effect. In some embodiments, the detection device is further programmed to detect at least one actuation of the retrieval device by the user at different actuation times, in particular after the blocking period. Alternatively or additionally, the detection device is programmed to detect a feedback point in time, preferably a last feedback point in time, after which there are no further actuations of the feedback device by the user, at least until the point in time at which the next application dose is dispensed. Optionally, the present invention also includes storing these feedback times. The control device can also be programmed to determine concentrations of the substance in the body, in particular in the blood, for example based on the data read out, such as e.g. B. PK curves, PK models, etc. Here, for example, both the concentration at the preferably first feedback time and the concentration at the preferably first actuation time (e.g. since the end of the last blocking period) or at the last feedback time relevant. These concentrations can be or will be assigned to the respective points in time. Furthermore, the control device can also be programmed to determine or select a concentration curve over time from a group of concentration curves over time. When determining the concentration curve over time, both the concentration at the preferably first feedback time and the concentration at the preferably first actuation time or the last feedback time are taken into account. Reference herein to a "set of concentration courses over time" means a set of concentration courses that relate to or are derived from the same dose (e.g. 50 µg fentanyl). In particular, the concentration profiles include those that reflect the time profile of the concentration for the mean value of all patients in a group examined using this dose, or the mean value plus/minus one or more standard deviations. A large number of such courses or data can be stored in the data memory. From this, the group of the observed time curves can be selected. Furthermore, the control device can be programmed to take into account the individual concentration profile over time determined in this way when predetermining the level of one or more of the subsequent application doses, in particular to take into account the determined individual PK curve. In some embodiments of the nasal applicator, the control device is further programmed to take into account the set target concentration or its maximum value when predetermining the level of the next application dose. Alternatively or additionally, it can be provided that the determined individual concentration profile over time, in particular the determined individual PK curve, is taken into account during the predetermination. In some embodiments, the controller is further programmed to, after delivery of an initial dose or loading dose at an earlier time, at a first (or referred to herein as "initial") time of actuation of the retrieval device by the user (preferably after expiration of an the blocking period following delivery of the initial dose, during which no application dose is administered to the user when the retrieval device is actuated), to determine a concentration assigned to this time of actuation, specifically for each of the concentration curves (stored in the data memory) of the/a group or of these derive. This first time of actuation is after the delivery time of the initial dose. The control device is also programmed to define the concentrations determined in this way as the estimated target concentration of the associated concentration profile over time. If, to put it simply, there was an initial dose and the user wanted to call up another application dose after the blocking period that followed had expired, then the point in time at which the user attempted to call up the further application dose is shown for each of the concentration curves considered over time a concentration assigned. Since the concentration so assigned has been determined by calculation and is the result of a hypothesis which still requires testing and confirmation, the concentration so determined is referred to herein as the estimated target concentration. If the group of time courses considered has three elements (courses), then three estimated target concentration values are obtained. In other words, three hypotheses are put forward. They indicate how high the concentration in the body would have to be if the first, second or third concentration course in the group applied to the user under consideration. An initial dose can also be referred to herein as a first or preceding application dose, which was delivered at a delivery time, which can correspondingly be the first delivery time. The initial dose may actually be the very first application using the drug delivery device. The control device can also be programmed to apply the first application dose following the initial dose in response to actuation of the retrieval device at the first actuation time. Furthermore, the control device can determine a point in time at which, after the application of this first application dose, the concentration in the body, in particular in the blood, will or should have fallen again to the estimated target concentration of the associated concentration profile over time. This time is also referred to herein as the calculated target concentration time. In order to calculate it in each case (i.e. for each concentration profile from the group), the same values are used again in each case temporal concentration curves of the group, for which a calculated target concentration time point has already been defined. It should be noted that differences between the level of the initial dose and the subsequent, first application dose are taken into account here. For example, if the initial dose was 50 µg fentanyl, the three selected concentration curves over time in the group indicated how this 50 µg fentanyl could be detected in the body. A first of the three concentration curves could e.g. B. assume that the course will behave as observed in a collective on average. A second can For example, suppose the gradient behaves like the first gradient by plus one standard deviation, plus 10%, and so on. A third can For example, assume that the gradient behaves like the first gradient by minus one standard deviation, minus 10%, and so on. However, if the subsequent, first application dose is not 50 µg, for example, but only 30 µg fentanyl, then the same three selected concentration curves over time for the group are assumed. They are just no longer calculated for 50 µg, but for 30 µg of fentanyl. The control device can also be used for direct or indirect detection or determination of the second actuation point in time for retrieving a second or subsequent, first application dose, e.g. B. second application dose to be programmed. In addition, the control device can be programmed to record a concentration over time from the group as an individual concentration over time, in particular to be determined as an individual PK curve. In this case, the respective difference between the calculated target concentration time of each concentration profile over time from the group and the second actuation time is taken into account. In particular, that concentration profile over time that has the smallest difference between its calculated target concentration time and the second actuation time comes into consideration as an individual concentration profile over time. The control device can also be programmed to take into account the determined individual concentration profile over time when predetermining the level of one or more of the subsequent application doses, which can in particular be an individual PK curve or an individual PK model. In some embodiments, the control device is further programmed to determine the concentration of the substance present in the body or in the blood of the user. The determination takes place at at least one considered actuation point in time or at least one considered predetermination point in time. Furthermore, the controller is programmed to set this concentration as the target concentration. The control device is further programmed to set the level of the next application dose at the next predetermined time such that the concentration in the body or in the blood of the user will only drop to the target concentration again after a predetermined period of time has elapsed. This period of time can be adjustable, for example by the attending physician, and begins with the delivery time of the next application dose. For this purpose, as described above, the unchanging individual concentration profile over time, ie the PK curve of the user, can be taken as a basis and/or taken into account. In some embodiments, the electronic control device is further programmed to take into account data read from the data memory in the step of predetermining the level of the next application dose. These data include both the delivery time of one or more of the application doses already delivered on the one hand and the amount of one or more of the application doses already delivered on the other hand. It is covered by the present invention that here, as an alternative to the delivery time, the time period elapsed between the one or more delivery times of the application doses already delivered and the delivery time after the next actuation time can be considered. In some embodiments, the evaluation of the activation behavior of the user, which is recorded by means of the detection device, includes the detection of activations of the retrieval device by the user at activation times within a blocking period. This can be in any, a specific, i. h, in the first and/or in the second, etc., or in each period of suspension. In certain specific embodiments, it is also optional to store this actuation behavior in or on a suitable device for this purpose, e.g. B. the data storage mentioned herein provided. The control device is also programmed to determine a concentration of the substance in the body, in particular in the blood, which is or can be associated with the respective actuation times within one of the blocking periods. The controller is further programmed to set a target concentration or its minimum value to a value above, below or equal to the associated concentration, respectively. In certain embodiments, the procedure outlined above may be repeated multiple times, e.g. H. in loop, to be executed. The target concentration so approximated, or the minimum value so approximated, may optionally be reset to zero (0) after any or each lockout period. In some embodiments, the detection device of the nasal applicator according to the invention is further programmed to detect and optionally store at least one actuation of the retrieval device by the user at least one time of actuation after the blocking period. In this case, the control device is further programmed to determine a concentration in the body, in particular in the blood, which is associated with the actuation time after the blocking period. The control device is also programmed to determine a concentration profile of the group over time. here both at least one, preferably the last, actuation time within the (any) blocking period and at least one, preferably the first, actuation point in time after the blocking period are taken into account. The control device is also programmed to take into account the determined individual concentration profile over time, in particular the determined individual PK curve, when predetermining the level of one or more of the following application doses. In some embodiments of the nasal applicator, the control device is further programmed to take into account the set target concentration or its minimum value and/or the determined individual concentration profile over time, in particular the determined individual PK curve, when predetermining the amount of the next application dose. In some embodiments, the evaluation of the actuation behavior of the user, which is detected by means of the detection device, comprises the evaluation of actuations of the retrieval device by the user at actuation times within one of the blocking periods. This can be in any, a specific, i. h, in the first and/or in the second, etc., or in each period of suspension. In certain specific embodiments, this actuation behavior can optionally also be stored in or on a device suitable for this purpose. Furthermore, the control device can be programmed to determine an increase in the time intervals between successive actuation times within a the (considered) blocking period, alternatively the absence of further actuation times within the considered blocking period. In addition, the control device can be programmed to specify a point in time from which the extent of the increase or the absence of it satisfies predetermined criteria. Criteria can be specified, for example, that as soon as z. B. 50%-75% of the lock duration T_vain_n have elapsed, one may assume that the actuation times are in a predetermined manner significantly further apart than before, and / or if for a, z. B. predetermined period of time has not been actuated, it is assumed that the effect of the therapeutic effect has become noticeable / noticeable and / or the target concentration has been reached. For some embodiments it can be specified that if arithmetically z. B. 80% or another predetermined proportion of the calculated maximum concentration has been reached and there are still unsuccessful retrieval attempts, i.e. the desired therapeutic effect has not yet been achieved, the end of the current blocking period is brought forward, since the remaining z. B. 20% of the concentration will not be sufficient to bring the user to the target concentration (C_ED) bring to. For some embodiments it can be specified that if arithmetically z. B. 80% of the calculated maximum concentration has been reached and there are still unsuccessful retrieval attempts, i.e. the desired therapeutic effect has not yet been achieved, the next predetermination time is brought forward in the knowledge that a retrieval attempt by the user will probably take place at the end of the blocking period. As these time intervals increase, it means that the desired therapeutic effect is beginning to set in, perhaps slowly, but definitely. Thus, in the event that an actuation by the user takes place after the end of the blocking period, the dose can turn out to be smaller or be calculated as if there were no therapeutic effect. Furthermore, the control device can be programmed to determine a concentration of the substance in the body, in particular in the blood, which is associated with the point in time. The controller may be further programmed to set the target concentration or its minimum value to a value above, below or equal to the assigned concentration, respectively. In some embodiments, the electronic control device is further programmed to evaluate at least one actuation of the retrieval device by the user at at least one actuation time which is after the blocking period. Optionally, storing the actuation in or on a device suitable for this purpose is also covered by the present invention. In this case, the control device is further programmed to determine a concentration in the body, in particular in the blood, for the actuation time or times after the blocking period. The control device can be further programmed to determine a concentration profile over time for the/a group, taking into account both one, preferably the last, actuation time within the blocking period and one, preferably the first, actuation point after the blocking period. In addition, the control device can be programmed to take into account the determined individual concentration profile over time, in particular the determined individual PK curve, when predetermining the level of one or more of the subsequent application doses. In some embodiments, the nasal applicator controller is further programmed to take into account the set target concentration or its minimum value when predetermining the level of the next application dose. Alternatively or additionally, the control device can take into account the determined individual concentration profile over time, in particular the determined individual PK curve. In some embodiments, the control device is further programmed to limit the level of the next application dose and/or to limit the resulting concentration. Alternatively or additionally, the control device is programmed to limit the cumulative level of all application doses delivered within a predetermined period of time and/or to limit the concentrations resulting therefrom. Again alternatively or additionally, the control device is programmed to limit the cumulative level of all application doses delivered and/or to limit the resulting concentrations. For this purpose, the control device optionally accesses data relating to the substance stored in the data memory. In some embodiments, the nasal applicator according to the invention is suitable for the nasal administration of an application dose of substances which are or have medicinal active ingredients in particular. In other embodiments, the inventions relate to a drug delivery device that is not a nasal applicator. What is stated herein for the nasal applicator therefore also applies without restriction to a drug delivery device as a nasal applicator, especially if this is portable and can be used by the user, e.g. B. a patient, alone actuable bar and is usually operated without outside help or special knowledge. In particular, a drug delivery device is suitable for other types of administration, for example for further transmucosal administrations, in particular via the oral mucosa, for example in the cheek pouch (buccal) or under the tongue (sublingual), for intravenous or also for inhalative administration. In some embodiments, the dispensing dispenser is or includes a particle or droplet generator, such as a vortex chamber, a spray head, a nozzle, cannula, dropper, perforated plate, baffle, porous membrane or the like. In some embodiments, the delivery doser includes an energizing mechanism and/or a delivery mechanism. This can be designed mechanically and/or electronically, e.g. B. as a micropump, piston pump, rotary pump, peristaltic pump, centrifugal pump or the like. In some embodiments, the dispensing doser includes an analog, in particular stepless, and/or a digital (0 or 1) control for dosing. This can be part of the electronic control device of the nasal applicator. In particular, an application dose or release quantity of the substance corresponds to a quantity in the range between 1 μL and 300 μL per actuation. In some embodiments, a high level of reproducibility and accuracy in the delivery of the amount by a user-independent operation (alternatively: triggering) by always the same trigger parameters such. B. tripping speed, tripping force, acceleration, flow rate, pressure, rotation, stroke, etc. must be guaranteed. In some embodiments, the nasal applicator includes a metering valve. In certain embodiments, the nasal applicator comprises an elastomer ring, in particular a removable one, for sliding onto a nose attachment (also known as a nose dip). The elastomer ring serves as possible hermetically sealing the nostril from an exterior. In some embodiments, the nasal applicator, e.g. B. commercial or conventional nasal spray cartridges that have an integrated conveyor or pumping device. By means of this integrated conveying or pumping device, different dosing sizes can be delivered after venting (priming), for example by lengthening or shortening the stroke of this device. In some embodiments, a delivery or pumping device is triggered mechanically, ie by hand, by the user/patient. For this purpose, for example, a spring accumulator can be loaded, adjusted and triggered manually or externally. In some embodiments, the dose detection device of the nasal applicator comprises a sensor configured to detect the substance delivered or the amount of active ingredient thereof. The dose or its volume or quantity can be detected, for example, by means of direct measurement, e.g. B. by means of a flow sensor, etc.) and / or by means of derived measurement. In the case of a derived measurement, the dose is calculated or derived. This can be done, for example, by measuring revolutions (rpm), angle, stroke distance, distance, number of strokes, time, valve actuations (number and/or time), etc. Alternatively or additionally, the dose can be detected by means of a spray sensor, which makes it possible to determine whether there are actually droplets of the atomized Form or forms fluids or aerosol in the area of the nose attachment. For example, the spray sensor uses the effect that the atomized fluid or aerosol scatters light and works as a so-called scattered light sensor. In some embodiments, the dose detection device can be integrated into the control device of the nasal applicator, for example. In other embodiments, it is separate. In some embodiments, the dose can be measured using a flow sensor, a flow sensor, or using a droplet distribution measurement and/or particle distribution measurement. In some embodiments, the droplet distribution and/or particle size distribution can be measured to determine the dose. In some embodiments, by means of the triggering parameters, such as e.g. B. triggering speed, triggering force, pressure, acceleration, flow rate, etc., the droplet size distribution and / or particle size distribution can be set or adapted or adjusted. This is intended in particular to adapt the droplet distribution and/or particle size distribution to different active ingredients in a simple manner. In some embodiments, the data memory of the nasal applicator comprises at least one internal memory component which is non-volatile and can be overwritten or written to multiple times and/or an external memory component which can in particular be exchangeable (e.g. SSD memory card, USB memory, HDD, etc.). Alternatively or additionally, a network, a smart device, a charging station (docking station) or the Internet can also be considered as external storage. In some embodiments, e.g. B. as a final step of the method triggered by the control device, at the end of the treatment or therapy without or after an automatic data backup in or on a (further) internal or external storage device suitable for this purpose, the personal data and / or individual control data from the Clear data memory of the nasal applicator and/or reset the nasal applicator to the factory settings. The nasal applicator or parts thereof can thus advantageously be passed on to other patients after the patient's therapy has ended, without data protection concerns having to oppose this. In some embodiments, the data memory, in particular the external data memory, can be implemented as a digital pain ID card and used by the user/patient to provide evidence to the attending physicians and/or controllers, for example when traveling or during checks. In some embodiments, the user/patient interacting with the nasal applicator can be viewed as a pre-programmed, self-regulating system, eliminating the need for programming and potential sources of error. The same is known from the use of IV-PCA smart pumps for the administration of opiates. The pre-programmed, self-regulating system includes certain dose limits (e.g. dose limits, concentration limits, time limits, limits based on a therapeutic effect, i.e. e.g. a lower dose for a low pain score). These dose limits may be dose limits per time, a specific number of actuations or actuations, a single dose limit, a daily dose limit, a concentration limit, and/or the like. When the dose limits are reached, two consequences can occur: the delivery of further application doses can either be paused or the dose can be reduced in such a way that a therapeutic effect can no longer occur. In particular, however, a placebo effect is made possible here. In some embodiments, the user/patient can be viewed as a control circuit and the triggering behavior of the nasal applicator can be adapted based on the recorded or determined pharmacological data in accordance with the user/patient reaction in terms of dose and therapy. On the one hand, direct measured values (actual values), e.g. B. the blood sugar level or the opioid concentration in the blood, or on the other hand indirect measured values (derived and/or estimated values), e.g. B. Pharmacokinetics ("PK-") curves of a (reference) population. Direct measured values are preferably used to adapt the triggering behavior. In some embodiments, the electronic control device is further programmed in order to be able to predetermine a predetermination time of an application dose of the substance, with subjective therapeutic observations of a patient-specific therapeutic effect, such as e.g. B. pain, to be considered. These observations can determine the level of pain (pain score). Pain type, pain duration, pain intensity and/or pain frequency of the patient. This means that the user/patient determines what is still bearable for him/her or how much pain he/she feels. This can e.g. B. by manual entry on a one-dimensional rating scale to determine the pain intensity. Such scales can be, for example: - a numerical rating scale (NRS, for example from 1 (= pain-free) to 10 (= strongest intensity)), - a verbal rating scale (VRS, with descriptions of pain intensity, for example "none", "moderate", "medium", "severe", "very severe", or also descriptions of the occurrence over time, for example "never", "rarely", "sometimes", "often", "always"), - visual analogue scale (VAS, for example as line whose endpoints represent extreme states, such as “no pain” and “unbearable pain”, on which the user/patient marks their subjective pain perception without perceiving a corresponding scaling), - Functional Activity Scale (FAS, e.g. with The classifications "no limitation" (no limitation) if the user can carry out a certain activity without limitation (eg due to pain), "mild limitation" (mild limitation) if the activity is only carried out with limitations can (e.g. B. due to pain) and "significant limitation" (significant limitation) if the activity is not performed (e.g. due to pain or side effects of pain therapy), or a - functional impairment such as e.g. B. insomnia, impairments in the ability to eat and/or drink and/or impairments in deep breathing. In some embodiments, objective and/or subjective observations may be considered. These can e.g. B. include: - Vital signs (such as blood pressure, heart rate, temperature, etc.), - Pupillary reaction, - Delirium - Hallucinations - Dizziness - Tolerance - Addiction - Increased sensitivity to pain (hyperalgesia) - Sedation (sedation), - Side effects (such as itching) , nausea (nausea), vomiting (vomiting) etc.), - physiological observations, - total dose/volume and/or total concentration of the substance/active ingredient, - remaining capacity in the container, - sleep patterns. In some embodiments, the present invention can be classified as part of the so-called Personalized Medicine, in which the user/patient is viewed as a pre-programmed, self-regulating system and with dose limits (absolute) and/or dose limits per time, concentration limits or quantity limits and/or limitation of the number of triggerings and/or limitations for a single dose and/or daily dose, etc. as well as the alternatives listed and explained below, the aim is to achieve therapy that is as individual as possible will. The more input or information about the status of the user/patient is available, the more individually the therapy can be designed. In particular, if concentration limits are considered here, different high doses can result in certain embodiments. In some embodiments, the electronic control device is further programmed in order to be able to predetermine a predetermination time of an application dose of the substance, patient-specific setup data being entered and/or taken into account as an alternative or in addition. This setup data can, for example, include or result from: - data from the (electronic) patient file, - data from the individual anamnesis, - data from a pre-operative consultation (pre-OP), - data collected during an operation (e.g. during a anesthesia), - data collected in a PACU (Post Anesthesia Care Unit, recovery room, etc.) and/or - individual anthropometric patient data (e.g. weight, age, height, sex, etc.) In some embodiments, alternatively or additionally, subjective therapeutic observations, e.g. B. by means of a Pain score entered and considered as described herein. In some embodiments, the electronic control device is further programmed in order to be able to predetermine a predetermination time of an application dose of the substance by alternatively or additionally taking into account objective therapeutic observations. These observations can be compared, preferably automatically, using sensor data for vital signs. The vital signs may include, for example: - heart rate (HR), - HRV, - (partial) blood oxygen saturation (SpO₂), - blood pressure, - blood pressure trending (BPT), - electrochemical skin reactions, - temperature, - photoplethysmogram (PPG), - electrocardiogram (ECG), - respiratory rate, - blood sugar level, - stress, - carbon monoxide (CO) measurement - electroencephalography (EEG). In some embodiments, there is the possibility of personalizing, adapting, modifying, etc. the methods initiated by the control device. This can be done by means of a user interface, management software and/or peripheral devices. In some embodiments, the method initiated by the control device creates value tables for controlling the nasal applicator. In some embodiments, the method initiated by the control device calculates different triggering parameters for the nasal applicator, depending on the position of the device. In some embodiments, the circadian, ultradian, and/or infradian rhythm of the user/patient may be taken into account. In some embodiments, the nose applicator transmits the data from the data store by cable, for example using a LAN, Powerline or PowerLAN, and/or wirelessly using appropriate protocols, e.g. B. Wi-Fi, Bluetooth, WLAN, GPS, RFID, NFC, barcode, QR code, ZigBee, Wibree, WiMAX, IrDA, WPAN, infrared etc. and/or is in signal connection with the data memory. If a signal or communication connection between two or more components is discussed here, this can be understood to mean a connection that exists during use. This can also be understood to mean that there is a preparation for such a signal communication (wired, wireless or implemented in some other way), for example by coupling both components, for example by means of pairing, etc. Pairing is a process to create a link between Manufacture electronic units for the purpose of communication. One of the most famous examples of this is the establishment of a Bluetooth connection, by means of which various devices (e.g. smartphone, headphones) are connected to one another. Pairing is also sometimes referred to as bonding. In some embodiments, the data listed here is transmitted via an interface between the smart device and the computer. In some embodiments, the data presented herein is transmitted web-based, i. H. no software installation is necessary. In some embodiments, the data listed herein is transmitted using an encrypted data transmission. In some embodiments, the data listed herein is preferably transmitted over an adjustable range. In some embodiments, low-energy solutions are preferably provided for the nasal applicator and the devices connected thereto in order to consume as little electricity as possible. In some embodiments, fleet management is provided for the nasal applicator and associated devices; H. managing, scheduling, controlling and monitoring multiple nasal applicators with the connected devices. In some embodiments, there is a possibility of integrating the nasal applicator, including the associated devices into an existing IT infrastructure. Interfaces, e.g. B. with clinical devices and / or with other medical products and / or with diagnostic devices and / or with a laboratory etc. can be provided. In some embodiments, interfaces to electronic patient files and/or to hospital quality reports and/or to national, European and international data collection initiatives or databases can be provided. Thus, on data from z. B. internal and external research, internal and external survey data (e.g. patient satisfaction, side effects, etc.) can be accessed. Within the European Union, for example, the international statistical classification of diseases and related health problems (ICD-10) is of interest, within Germany the diagnosis-related case groups (Diagnosis Related Groups (DGRG)) and quality improvement in the post-surgical pain therapy (QUIPS) provide comparative data and in the USA the programs of the Risk Evaluation and Mitigation Strategies (REMS), the DEA monitoring programs or the DEA documentation.In some embodiments, a modular/expandable dock or a docking station for the nasal applicator or the electronic control unit thereof and/or other peripheral devices. The dock or docking station is used for storage and/or management of the nasal applicator and/or peripheral devices. The dock or docking station is for storage and/or or management of the applicator and/or peripherals suitable. The dock can e.g. B. for loading, for software updates, pairing, hardware checks and / or releases, etc. may be provided. The dock or docking station also counts as a peripheral in some embodiments. In some embodiments, the dock or docking station is optionally not used for data transfer between the dock or docking station on the one hand and a nose applicator that is in physical contact with it and/or a server or cloud server on the other hand, but in others it is. In some embodiments, the dock or docking station is implemented as a standalone IT infrastructure, e.g. B. in the Internet or intranet (via hub / router / switch), provided. Alternatively or additionally, the dock can be integrated and/or integrated into an existing IT infrastructure via appropriate interfaces. In some embodiments of the present invention, the data interfaces are wired, e.g. e.g. designed as USB, USB-C, Thunderbolt, LAN, etc. In some embodiments it can be provided that e.g. B. IBM Watson to create access to outsourced system intelligence and thus provide connection to existing hospital information systems (HIS/PACS) via common interfaces such as HL7 and DICOM. For example, a technician can thus have access to the nasal applicator, to the devices connected to the nasal applicator, to interfaces and/or to the software. In some embodiments, a central server is provided. In some embodiments, the nasal applicator, in particular its electronic control device, comprises an energy storage device, in particular a rechargeable accumulator or a battery. In some embodiments, the energy storage device can have an application-related and/or indication-related battery design. In these embodiments, depending on the indication, a differently dimensioned energy storage device can be provided, in particular energy storage devices with different service lives or different running times. For example, an energy supply of three days may be sufficient postoperatively, while a longer energy supply (e.g. over two weeks) may be advantageous in the treatment of migraine. In some embodiments, wireless charging of the energy store can be provided, for example by means of pins (e.g. in a charging cradle) or without pins (e.g. Qi, by means of inductive energy transmission). In some embodiments, wired charging of the energy store can be provided, for example by means of a power pack or by means of Power over Ethernet (PoE). In some embodiments, batteries can be provided for changing as the energy storage device, e.g. B. Disposable batteries (button cells, AA, AAA, AAAA, block batteries, etc.), rechargeable batteries, rechargeable battery packs, etc. In some embodiments, an external power connection can be provided as the energy store, or PoE can be used. In some embodiments, a solar cell can provide the necessary energy. The solar cell can be attached directly to the nasal applicator or e.g. B. be provided on a loading dock or a charging station. In some embodiments, the necessary energy can be obtained by means of a winding mechanism, for example like a clockwork, or by means of so-called "energy harvesting", i. H. for example by pressing a button or a lever one or more times. The energy gained in this way can be used immediately or later for the application of application doses. In some embodiments, the substance reservoir of the nasal applicator is provided integrally, in other embodiments not integrally, in particular co-packed, i. H. packaged with the nasal applicator and/or an associated component. Both in the integral and in the non-integral embodiments, the substance reservoir can be (re)filled, in particular from the outside. In some embodiments, the substance reservoir is an already prefilled disposable container and/or a disposable container that can be filled on site, e.g. B. made of glass, plastic, metal, non-ferrous metal, composite materials, etc. or a combination of these materials. In some embodiments, the substance reservoir is provided with a position-independent triggering device, i. H. triggering can take place with a triggering functionality in all axes and degrees of freedom. This can be implemented, for example, by a collapsible and/or an energy-loaded container and/or the like. In some embodiments, the substance reservoir has a fixed filling volume, in other embodiments it has a variable filling volume. In some embodiments, the substance reservoir can be free of preservatives, in other embodiments it can be filled with substances containing preservatives and/or be suitable for this purpose. In some embodiments, the substance reservoir is provided with at least one connection device, which is used to connect the substance reservoir to the dispensing dispenser, in particular in a detachable manner. This can be done by means of a Luer connection, a needle, a screw cap, a plug connection, a click connection, by means of compression or the like. Furthermore, mechanical pins and/or a form fit can also be included in the present invention for the connection. In some embodiments, a device, in particular a barcode/QR code and/or an RFID device, can be provided on the substance reservoir for recording and/or storing information that can be output for the traceability of one or more applications. These can also e.g. B. a label, a QR code, a chip, an RFID / NFC tag, an image recording, which can each be scanned, etc. or a combination thereof. Applications are, for example, information about the substance such as name, expiry date, pharmacological data, concentration, etc. In some embodiments, technical solutions can be used on the substance reservoir to avoid errors in the sense of the poka-yoke or key-and-lock principle. For this purpose, for example, an inscription, a QR code, a barcode, a chip, an RFID/NFC tag, an image recording, which can each be scanned, etc. or a combination thereof can be provided on the substance reservoir. Corresponding control and/or computing devices with suitable software can also be included in the present invention for this purpose. This allows u. advantageously improper handling and/or the insertion of an incorrect substance reservoir into the nasal applicator can be avoided. Mechanical pins and/or a corresponding form fit can also serve this purpose and are therefore also covered by the present invention. In some embodiments, the substance reservoir is a non-integral, pre-filled, disposable container, e.g. B. made of glass, plastic, metal, non-ferrous metal, composite materials, etc. or any combination thereof, which is stored separately from the nasal applicator, in particular from its dispensing dispenser. In particular, this avoids compatibility problems between the material(s) of the substance reservoir of the substance. Separate storage increases the risk that extractables or leachables migrate into the substance, be reduced or even avoided. In some embodiments, the substance reservoir is a refillable, integrated reusable container with a filter, in other embodiments without a filter. In some embodiments, the substance reservoir is an external reusable container with a filter, in other embodiments without a filter. In some embodiments, the nasal applicator includes an additional substance reservoir, in particular a liquid reservoir, in which another substance can be accommodated. The further substance preferably differs from the first substance. The further substance may be medicinal or non-medicinal, e.g. B. hyaluronic acid, ectoine, aloe vera, etc. In some embodiments, the nasal applicator or its substance reservoir comprises multiple fluid chambers, such as the aforementioned second fluid chamber. In such embodiments, the nasal applicator may be capable of delivering multiple therapies, e.g. B. painkillers or cannabinoids on the one hand and z. B. and insulin on the other hand to support. In certain embodiments it can be provided that the substance in the second fluid chamber and/or in the substance reservoir is neutralized or destroyed with a fluid from the second fluid chamber and/or in the substance reservoir, or vice versa. This can be particularly useful in the event of theft or misuse. For this purpose, in the second fluid chamber and/or in the substance reservoir For example, a desiccant can be provided, which the substance and thus the active substance contained in it passes through (similar to the principle of a filter or coffee filter) or by which the active substance or the substance is absorbed (e.g. like a sponge) and the desiccant absorbs the substance or the Active substance (e.g. its salt) binds. The desiccant can e.g. B. in a filter, the second fluid chamber or a sponge, z. B. be provided as granules. The desiccant may also be maintained elsewhere in the nasal applicator, preferably such that the substance containing the active ingredient passes through or is stored in or resides in the desiccant if desired. Desiccants can e.g. B. sodium sulfate, calcium sulfate or calcium chloride. As a filter z. B. a molecular sieve, a filter fleece or an ion exchanger can be provided. Desiccant, in particular as discussed above, can additionally or alternatively also be arranged at a different point in the housing. So not limited to the second chamber and/or the substance reservoir. In some embodiments, the nasal applicator includes a cooling device suitable for cooling one, several or all substance reservoir(s), in particular its content. In certain embodiments, the nasal applicator comprises a heating device suitable for one, several or all Substance reservoir (s), especially its content or contents to heat. This is particularly advantageous for preventing the substance from freezing or for preventing the substance from being degenerated/destroyed by cold. In some embodiments, the control device may be provided as a disposable device, in other embodiments as a reusable electronic control device. Hybrid embodiments, in which part of the control device is reusable and part is provided as a disposable component, are also encompassed by the present invention. In some embodiments, the control device collects, stores, monitors, processes, calculates, simulates, regulates and/or controls one, several or all functionalities of the nasal applicator. In some embodiments, the nasal applicator is controlled by the control device using an algorithm (embedded software) that is loaded onto the nasal applicator. In some embodiments, the dispensing doser can be controlled separately by the control device or together with the dose detection device. In some embodiments, the dose detection device can be controlled separately by the control device or together with the dispensing doser. In some embodiments, the nasal applicator is controlled by the control device using a decentrally stored algorithm, e.g. B. web-based, via a ward computer or smart devices (non-embedded software). In some embodiments, the control device is in wireless or wired signal communication with other devices, for example in order to be able to interact with peripheral devices; corresponding transmitting and/or receiving devices can be provided. They can be in signal communication with the control device. The peripheral devices can include include: - devices for patient authentication, - wristbands, - sensor arrays, - docking stations, - computers (PCs), - smart devices, - printers, - other medical devices, - devices in a data center, - hub, router, access point, - servers, - (Cloud) servers. The system according to the invention can have one or more of the aforementioned and/or other peripheral devices. In some embodiments, peripheral devices of the nose applicator function as radio cells for a positioning system or for generating a geofence. A geofence is a virtual fence or boundary that "encloses" a physical location. Like a real fence, a geofence separates a location from its surroundings - albeit in a digital way rather than in the form of a physical barrier. In contrast to a real fence, however, a geofence can optionally also detect movements within the "fence". Such a virtual fence can be of any size, shape or peripheral coupling. Even a straight line between two points can be possible and intended. Geofences are e.g. B. created with the help of a map software and allow the user to draw the virtual fence directly over the desired area and / or using GPS, W-LAN, WPAN, RFID, Bluetooth signals and / or other peripheral devices to create coupling etc. The digital limit consists z. from a number of coordinates for latitude and longitude - and in the case of a circular geofence only from one point forming the center by means of W-LAN, WPAN, RFID, Bluetooth signals and/or with other peripheral devices a pairing etc Geofences can be used to identify objects within the virtual fence, e.g. B. by using W-LAN, WPAN, RFID, Bluetooth signals and / or other peripheral devices coupling etc. tracking to monitor and / or define specific action for an area and / or activate. In this way, one recognizes immediately, for example, when a device such as the drug delivery device according to the invention, in particular the nasal applicator, has left its place of use Will get removed. Conversely, virtual fences can also be used to keep objects out of a certain area. In some embodiments, the electronics of the control device can be designed redundantly, e.g. B. two-channel, by monitoring system / watchdog, etc. This can contribute in a particularly advantageous way to ensure safe operation, thus increasing safety and to meet the various risk classes in medical technology. In some embodiments, the nasal applicator retrieval device includes a triggering mechanism, which in turn includes at least one of the features described below. Thus, the triggering mechanism can work purely or essentially mechanically, e.g. B. similar to an insulin pen or a Respimat^® Soft Mist Inhaler. Alternatively, the triggering mechanism can be a combination of mechanics (triggering mechanism) e.g. B. heart curve, actuator and / or skip and electronics (control). In some embodiments, the triggering mechanism may be or include a unidirectional, bidirectional, multidirectional, rotary, stepper, and/or encoder controlled, and/or infinitely variable piston and/or actuator, etc. In addition to this, an opposing dosing adjustment mechanism (cf. insulin pen) can be provided in some embodiments. Alternatively, electronic dosing (cf. electronic insulin pen) is also covered by the present invention. In some embodiments, the triggering mechanism includes a pump, e.g. B. a micropump, piston pump, rotary pump, peristaltic pump, centrifugal pump, centrifugal pump or the like. In some embodiments, the triggering mechanism is based on a bi-directional two-stroke (suck/push) principle, e.g. B. according to the functional principle of the Respimat^®s. In some embodiments, the dispensing device or triggering mechanism may induce microdosing, e.g. B. in the range of 1 µL to 300 µL. In some embodiments, the dispensing device or triggering mechanism may be programmed or configured to deliver a dosage or dose per unit of time, e.g. B. 100 µL / sec. In some embodiments, a delivered amount (application dose) can be easily and/or accurately reproduced since the amount or scope of the application dose is independent of user/patient manipulation by means of the present invention. A high level of reproducibility and accuracy of the dispensed quantity through user-independent triggering with always the same triggering parameters, e.g. B. force, speed, acceleration, pressure, flow rate, stroke / distance, general energy input can contribute advantageously to patient safety. In some embodiments, the triggering mechanism may cause triggering by a mechanical or electronic trigger. In these embodiments, no force is required in the system. In some embodiments, the application dose of the substance is adjustable, in particular variable, in particular by means of configurations of the triggering mechanism, as described herein. In some embodiments, the substance resides in a print cartridge. In some embodiments, the cloud of droplets is generated by means of vibrating mesh, piezo, porous materials and/or evaporation. The output quantity can be set over time or a pre-dosed quantity, which is then atomized. In some embodiments, the triggering mechanism includes a metering valve that remains open as long as it is held depressed, for example. A dosing valve with a dosing chamber, a time-controlled valve, or a flow-controlled valve, etc. is also encompassed by the present invention. In some embodiments, the manually adjustable mechanism for changing the capacity of the dosing chamber z. B. by means of a knob, designed as a ratchet or the like, with z. B. a numerical scale or information on the delivery amount, dose, etc. The attack of the ratchet against an energy store, z. B. a spring or an elastic element, act or not. The triggering or deployment is z. B. triggered manually in the same way as a classic nasal spray. After the application has been completed, the ratchet slides into the new starting position of the stopper, for example via a lock nut or the like. The dispensing device may or may not be connected to the plug, e.g. B. by a piston. In some embodiments the mechanism is manually adjustable, in others it is automatic or a combination of manual and automatic or semi-automatic. This applies to any embodiment of the mechanism falling under the invention. In some embodiments, the retrieval device may be arranged laterally. In some embodiments, the "ratchet" may be a conventional ratchet. It can have an opposing thread. Again, this may apply to any mechanism mentioned herein. In some embodiments, the mechanism for changing the capacity of the dosing chamber can simultaneously charge an energy store, for example in the form of a spring store, and by means of the Apply retrieval device, which releases the energy storage. In some embodiments, the dose setting or the dose application can be a combination of manual and automatic procedures. In some embodiments, the substance reservoir also represents the dosing chamber. This means that the substance reservoir is used to apply directly or indirectly via the nasal attachment, without the application dose to be administered first being received in a chamber or dosing chamber that is fluidically at least temporarily separated from the substance reservoir. An independent assembly device is therefore not required in these embodiments. In this way it can advantageously be ensured that the dispensing device always moves, rotates, conveys in the same direction, which allows the inevitable play to be compensated for in a simpler way than if a left-right movement, an up-down movement were carried out. Based on the measurement results of an optional flow sensor or an optional device for quantity detection, etc. of any kind, in some embodiments the motor can be controlled for spreading, for example by simply switching off the power supply or giving the controller a corresponding signal, in particular to switch off. In some embodiments, another configuration is provided, in which z. B. manually die Application dose or its amount adjusts. For example, an energy store is manually tensioned and triggered manually. In some embodiments, the deployment device can drive a separate plug, alternatively the plug can be integrated into the deployment device. In some embodiments, in particular in the case of a single-use device, the stopper and fitting device can be permanently connected to one another and/or integrated into one another. In other embodiments, particularly in a reusable device, the plug and pick-and-place device can be in two parts, or the spindle and plug can be detached from one another. In some embodiments, the nose attachment can be designed integrally with the housing or connected to it, for example plugged on, screwed on or the like. A connection point can be provided for this purpose. It may be located inside or outside an enclosed lumen of the housing. In some embodiments, the dispensing device has a piston with a stopper at the end, which moves into the substance reservoir, which in these embodiments can also serve as a dosing chamber. In some embodiments, a servomotor is arranged to move or adjust a stop, for example by means of a spindle or set screw. In some embodiments, the stop, which could alternatively be intended to be adjusted manually, limits the travel of a trigger mechanism. In these embodiments, the triggering mechanism can be understood as part of the deployment device. In some embodiments it can be provided that the triggering mechanism is preloaded by means of a spring accumulator, a spring or another energy store, and is triggered in the preloaded state, e.g. B. manually. Alternatively, the triggering mechanism may be motor driven and/or triggered. In some embodiments, the stop may be configured by an internally threaded outer ring which may be slidably provided along an externally threaded cylindrical guide. In some embodiments, the stop can be provided to be displaceable or adjustable by motor and/or manually. In some embodiments, the retrieval device may be in the form of a terminal push button that is pressed against a spring. In some embodiments, a valve can be a check valve or a valve that only opens at a certain pressure, e.g. B. from 4 bar pressure, and after the pressure drop below 4 bar closes again. In some embodiments, a filter may be provided at the end of the metering chamber or after the connection point. In some embodiments, the dosing chamber is adjusted using an inclined plane. A suitable mechanism can be provided for this purpose. The triggering and application can take place in the same way as with a classic nasal spray. An optional device such as a return spring can return the dispensing device and/or other components to their initial position. In some embodiments the setting/adjustment of the mechanism can be done manually or automatically by e.g. B. engine. The movement can be rotational or linear. In some embodiments, the substance reservoir can be designed with trailing stoppers, a pouch bottle, a “bag”, a reservoir with a riser tube, etc. In some embodiments, the mechanism for changing the volumetric capacity of the metering chamber may be integrated into the nosepiece or may be located before or after the port. In some embodiments, the mechanism for changing the volumetric capacity is the dosing chamber itself. In some embodiments, the stopper includes or consists of the piston which is driven into the substance reservoir by gas under pressure in a pressure vessel. When the retrieval device is actuated or depressed, an application dose as provided in the dosing chamber is delivered. In some embodiments, the dosing chamber is defined by means of inclined planes or the like, such as e.g. B. attacks and the like set. When the retrieval device is triggered manually, the gas pushes the piston with the stopper forward and into the substance reservoir. In these embodiments, too, the setting and triggering can take place manually or automatically. In some embodiments, the inclined planes can e.g. B. linear or circular (curved). In some embodiments, the dosing chamber or its volume is set using an inclined plane(s) and a motor, which could alternatively be done by hand. In these embodiments, the spring accumulator is loaded or preloaded manually; this could alternatively be done by means of a motor or other energy sources. In some embodiments, the triggering is implemented by means of a spring accumulator. In these embodiments, the stroke can be adjusted automatically or manually and/or the triggering z. B. take place manually, for example by rotating the spring-loaded mechanism manually or automatically. In some embodiments, this rotation can be implemented by means of a motor. In some embodiments, the mechanism for changing the capacity of the metering chamber for the application dose of the substance is adjustable. In some embodiments of the nasal applicator, it has a pump, in particular a micropump, which is preferably not coupled directly to the vortex chamber, which can be present in the nose attachment, but rather fills the dosing chamber with the desired delivery quantity or application dose from the substance reservoir. In some embodiments, the pump fills the dosing chamber. In some embodiments, the pump may connect directly to the interface or nosepiece. In some embodiments, the dosing chamber can also be opened manually, e.g. B. ratchet, or automatically, z. B. by means of a motor. The pump switches z. B. after reaching a certain pressure or time or is stopped or switched off. In some embodiments, a flow sensor that controls the pump can be used for this purpose. In some embodiments, the substance introduced into the dosing chamber by means of a pump displaces the piston delimiting the dosing chamber, thereby increasing the capacity of the dosing chamber. In some embodiments, a non-return valve can delimit the dosing chamber in such a way that substance flows from the substance reservoir into the dosing chamber can, but not through the non-return valve out again. In some embodiments, the pump, which is or may be part of the pick-and-place device, may be motor driven or alternatively may be hand driven e.g. B. by means of a knob or a lever. The numbers that can be provided on the rotary knob in these embodiments can indicate the set or adjustable dose amount. In some embodiments, a spring accumulator may be spring loaded or charged manually or by the motor. If this is triggered, the application quantity is pressed through the vortex chamber of the nose attachment. A trigger may be provided in some embodiments. He has the function of the retrieval device. For example, he can wake up the system from standby and load the next dose (i.e. fill the dosing chamber). In some embodiments, the trigger can be mechanical or electrical. A ratchet can be released by means of the trigger or a signal can be sent to the electrical control device, which then releases an actuator. In some embodiments, a valve, which may or may not be integrated with the check valve, seals the joint. To fill the dosing chamber, this valve is closed and on other valve open. As soon as the dispensing device moves, e.g. B. in the direction of the connection point, the check valve closes. Now all valves are closed and pressure builds up in the chamber. In some embodiments, one or more of the valves present may be either electrically switched, open at a minimum pressure, and/or manually opened via the retrieval device. In certain embodiments, the retrieval device can assume different detents depending on whether, or depending on how much (to what degree) the metering chamber is filled. In some embodiments, a spring can be provided which presses on the stopper. In some embodiments, the housing of the nasal applicator has a cover which, in its open state, reveals the interior of the housing, so that z. B. the substance reservoir, which is optionally designed as a vial, can be removed from the housing and, for example, replaced by another one. In some embodiments, a needle can be provided for establishing a fluid connection between the dosing chamber and the substance reservoir. B. pierces a septum of a vial. The pump can in turn be driven by a motor, alternatively this is done manually. In some embodiments, the pump, the mechanism for changing the volumetric capacity of the metering chamber and/or the charging of the spring accumulator can be operated by means of a motor. The motor can optionally drive the deployment mechanism or the deployment device. All of these components can be provided and designed to be operated and/or controlled manually or automatically in any combination. In some embodiments, a non-return valve is preferably provided on an end area of the piston (dispensing device), which closes when the product is discharged (piston moves in the direction of the cover). At the opposite end region, i. h near the connection point, a valve is provided which can be switched or is closed when the metering chamber is being filled by the pump and opens when the piston (dispensing device) moves towards this valve. This can be implemented by means of a switchable valve (electrical or mechanical), which opens when it is triggered. The same could also be implemented with a check valve, which only at a certain pressure, z. B. 4 bar opens. Then, when filling the dosing chamber with the pump, this valve would remain closed until the pressure in the dosing chamber exceeded the opening pressure of the valve—similar to a pressure relief valve or pressure sequence valve. In some embodiments, the pump fills the metering chamber, and by means of the resulting increase in pressure the loading device and/or the dispensing device are pushed away from the connection point. In doing so, e.g. B. loaded a spring energy storage. The energy stored in this way is then used to move the deployment device in the direction of the connection point. In some embodiments, the motor can drive the pump, the loading device and/or the dispensing device. In some embodiments, the orientation of the vial, e.g. B. 180 ° rotated. In some embodiments, the triggering mechanism further includes or enables a reversible pumping (priming) direction. This can in particular z. B. for the disposal and / or neutralization of the substance or the active ingredient in case of misuse and / or theft. For example, an air pump or another delivery mechanism or actuator can be provided, which pushes the stopper of the substance reservoir out of the reservoir and thus the substance comes into contact with the desiccant, whereby the former can be bound by the latter. In some embodiments, the housing of the nasal applicator functions as a retrieval device for actuating the trigger mechanism. In some embodiments, the nasal applicator is suitable and/or adapted for operation by right-handed people, in others for operation by left-handed people. In certain embodiments, he is due for both service Suitable and/or adapted for left-handed and right-handed use. In some embodiments, the triggering of the triggering mechanism and/or the level of the administration dose caused thereby are independent of an actuation by the user/patient. In some embodiments of the nasal applicator it is provided that the user/patient sets the amount of an application dose to be delivered himself. This can be done, for example, based on calculations or instructions from a doctor. These can be communicated to the user/patient in different ways, for example via a smartphone or the like. In certain embodiments, software, in particular an application (app), for example for a smartphone, can be included in the present invention for this purpose. In some embodiments, the retrieval device for activating the trigger mechanism comprises at least one of the following devices or is configured as such: an integrated trigger button, for example configured as a soft-touch button, as a push button, as a switch, as an area (button) on a touch screen, as a sensor or similar; - an integrated input device, e.g. a keyboard, a touch screen, a rotary knob (or more), an integrated sensor or a camera for capturing biometric data, e.g. fingerprint, face or voice, a code, or the like; - An external input device, which is preferably wirelessly connected to the nasal applicator, in particular its retrieval device, for example an application (app), a remote control, input via web or cloud, computer, smart device or the like. In certain embodiments, the external input device can be configured analogously to the examples of the implementation of the integrated input device mentioned herein. In some embodiments, certain user/patient behavior may control or affect the retrieval device. For example, pressing twice for a trigger can cause the nasal applicator to "wake up" with the first press, possibly combined with a system check, a check of authorization, etc., a calculation of the application dose and provision of the same, while the second press finally triggers the application dose causes. In some embodiments, the nasal applicator can generate output information, in particular by means of one of its devices, preferably automatically, preferably after a substance dose has been dispensed. This output information can be or can include a log file of the treatment. Each detectable signal or each detectable interaction, in particular each actuation, can be logged. Alternatively or additionally, the output information can be or include the creation of a standardized and/or personalized report related to the user/patient. The output information can be displayed using a digital (online) dashboard, using print functions (e.g. for the narcotics book (BtM)), by means of exports, etc. to a suitable device for this purpose, preferably wirelessly, in some embodiments also wired and/or with contact pins. In some embodiments, the delivery dose triggering mechanism may be activated in other ways, such as breath-activated or nose-activated, i. H. the triggering mechanism is automatically activated by means of a negative pressure sensor, for example, when the nasal applicator is inserted into the nose and inhaled through the nose. A mechanical implementation of this triggering mechanism is also covered by the present invention. In some embodiments, an optical system is integrated into the nose applicator, for example for capturing biometric data such as a fingerprint or face, for capturing a QR code, a barcode or the like. In some embodiments, the output information may be or may include an indication of the amount of time (countdown/timer) until the next release. The display or the expiry of this period of time can, for example, be optical (e.g. by means of a colored display, an LED or a push message), acoustically (e.g. by means of an alarm), tactile (e.g. by means of vibration) or on be done in an analogous manner. A colored display can include, for example, the nasal applicator or a section thereof changing color to signal its status, for example changing to “green” if a new application is allowed to take place. In some embodiments, the output information can be or include an output of step-by-step instructions (e.g. for setup or further operation or the like) using a visual and/or acoustic medium, for example a smartphone or the like. In some embodiments, step-by-step instructions are provided on the nasal applicator and/or on corresponding peripheral devices and/or on smart devices. In some embodiments of the present invention, input and/or output options can each be provided in a barrier-free manner. This includes e.g. B. inputs and / or outputs in Braille, optical, acoustic or tactile inputs and outputs, z. B. vibration, sound, etc. This is particularly advantageous for the use of the present invention in poor visibility conditions and / or at night. These input and/or output options can in particular be or include contactless input and/or output options. In some embodiments, the nasal applicator includes a QR code reader. This can be used to scan the UDI (“Unique Device Identification”) of the disposable cartridge, to identify the disposable housing, the applicator electronics, a disposable wristband and/or its wristband electronics, and/or for automated reading in a docking station. In some embodiments, printer functionality is also encompassed by the present invention. This can include serve to create a report, to produce stickers (e.g. for the BtM book and/or the patient file), etc. In some embodiments of the present invention, data access is provided directly by means of a dedicated input and read-out display. Alternatively or in addition, data access can be provided indirectly using “digital online management software”, for example using a smartphone, tablet and/or computer and/or using other interfaces. In some embodiments, the nasal applicator and/or at least one of its devices includes touch-sensitive surfaces. In some embodiments, the present invention may include a microphone integrated into the nasal applicator and/or a smartphone microphone. This microphone can be used to z. B. to record a pain diary. In certain embodiments, the present invention may include a shake to wake function. Devices suitable for this purpose, for example an acceleration sensor, a gyroscope, an angle sensor, a position sensor and/or the like are also covered by the present invention. In some embodiments, the devices mentioned are additionally provided to detect improper handling of the nasal applicator, for example a fall, shock, vibration, excessive pressure on the applicator, rough handling or the like. In some embodiments, the present invention may include a camera integrated into the nasal applicator and/or a smartphone camera. This camera can be used, for example, to be able to look into the nose, ears, etc., to have a diagnosis made after transmission to a doctor, and the like (digital health diagnostics). It can also be used to identify the degree of sedation, for example by recording a pupil reaction of the eye. Patient authentication means that only the authorized user/patient can operate the device. A user can e.g. for example a doctor, a nurse and/or another authorized person. In some embodiments, the nose applicator has an integrated authentication module for this purpose, in other embodiments the authentication module is provided externally, in certain embodiments partially integrated. In this case, the authentication mechanism on which the authentication module is based is preferably coupled to exactly one single, specific device. Signal transmissions required for this purpose can e.g. e.g. be provided and take place as disclosed herein. Appropriate configurations of the signal transmission partners involved can be provided. In some embodiments, an integrated authentication module, i.e. provided on or in the nose applicator, can have an optical effect, e.g. B. by means of QR code readers or by means of devices for recognizing and comparing biometric data, in other embodiments it can have an acoustic effect, e.g. B. by voice recognition, in further embodiments tactile, e.g. B. by entering a PIN or a password. In this case, the authentication module comprises the sensor arrangement that is suitable in each case for authentication and an evaluation device. In some embodiments, the authentication module may be provided to be compatible with other devices, devices, devices. Provision can be made in certain embodiments for authentication to be carried out by means of vibration (for example by means of a specific vibration pattern) or by means of speech or voice recognition. In further embodiments, an area in which the device is enabled can be defined via the GPS location of the nose applicator and/or by means of a geofencing function. In some embodiments, a partially integrated or external authentication module can be provided on the patient, in other embodiments it is not provided on the patient. For example, with partially integrated or external authentication modules, the authentication mechanism can be based on tokens, wireless authentication. The authentication module can be a wristwatch, an RFID wristband, a barcode/QR code, a chain, a ring, a smartphone, a smartwatch, a tablet, or additional software for the aforementioned modules (e.g. an app), etc. be or include. In this case, the authentication module comprises the sensor arrangement and/or evaluation device suitable for the authentication in each case, analogously to that described above. In some embodiments, the authentication module is compatible with standard hospital patient identification tools, e.g., it can be affixed, printed, or integrated (e.g., in a patient wristband). In certain embodiments, the standard hospital patient identification tool itself serves as an authentication module, such as the printed barcode/QR code. In some embodiments, it may be necessary to use the authentication module to authenticate an administrator and/or a user group in order to put the nasal applicator into operation or trigger an application dose or make adjustments to the nasal applicator. In some embodiments, the authentication module is provided to additionally authenticate technicians and/or system administrators and grant them access to the software of the nose applicator, in particular its control device. In some embodiments, it may be necessary to use the authentication module to authenticate an administrator and/or a user group in order to operate the nasal applicator control device by remote control or remote control (remote) and/or to overwrite data on it (override function). This can e.g. B. be necessary to cause an extra drug delivery. Authentication can be carried out here by means of one of the devices and/or modes of action mentioned herein. In some embodiments, the range of the authentication module is variable and/or adjustable, preferably continuously. In some embodiments, the authentication module can be integrated in so-called smart textiles, for example in glasses, in shoes, in a patient gown, in a pillow and/or in a pillow case and/or in a duvet cover and/or mattress, in a work coat or the like . In certain embodiments, the authentication module can also be attached to the edge of the bed, on a bedside table, in a socket near the patient. In some embodiments, the authentication module is an in-ear wearable device or the like. In some embodiments, the authentication module is or comprises a subcutaneous implant for authentication and a sensor arrangement suitable for reading the same. In some embodiments, the authentication module is or includes a dental crown or dental splint for authentication and a sensor arrangement suitable for reading the same. In some embodiments, the authentication module is or includes a camera integrated into the nose applicator and/or a smartphone camera to capture data, for example biometric data, alternatively or additionally a microphone, integrated or external, for the purpose of voice recognition. In some embodiments, the nasal applicator comprises a monitoring/surveillance system, with monitoring being or comprising observing the patient and monitoring also observing his surroundings. By means of the system, for example, the so-called adherence to therapy, i. H. the extent to which the patient's behavior is in accordance with the agreed recommendations/prescriptions of a doctor (compliance/adherence) are monitored. In some embodiments, the monitoring/surveillance system includes real-time automated drug monitoring. This can e.g. B. record a used amount, a remaining amount, the number of remaining applications, etc., and store it internally or externally using a storage device suitable for this purpose. In some embodiments, the monitoring/surveillance system includes automated real-time therapy monitoring. This can e.g. B. application times and application quantities, attempted (unsuccessful) applications during a blocking interval, etc. and store them internally or externally using a suitable storage device. In some embodiments, the monitoring/surveillance system includes automated real-time therapy log keeping. This can e.g. B. patient-specific side effects, emotional states and / or the strength, duration and / or frequency of symptoms etc. and store them internally or externally using a suitable storage device. In some embodiments, the monitoring/surveillance system can be designed to create a mobility log. In some embodiments, the nasal applicator monitoring system includes a combination of the aforementioned real-time monitors. Real-time monitoring using the monitoring and/or monitoring system of the nasal applicator advantageously enables simple and/or precise logging of the therapy. In some embodiments, the control device of the nasal applicator includes integrated, optical and/or acoustic status and/or alarm displays, for example LED( s), buzzer, beep(s) and/or a display to indicate the status or the alarm, in particular by means of an error code or the like. In some embodiments, the control device of the nasal applicator includes external, optical and/or acoustic status and/or alarm displays, for example in or on peripheral devices, smart devices and/or ward computers. The external status and/or alarm indicators can also LED(s), buzzer, beep(s) and/or a display, and they can also be provided as a software dashboard (app), push message or the like. In some embodiments, the nasal applicator is configured to send automatic notifications, in particular a call for help and/or an alarm to third parties, e.g. B. to certain groups of people, doctors, nursing staff, rescue control center or the like. This can be the case, in particular, in the case of unusual behavior, such as deviations from stored movement profiles or patterns, or, for example, constant retrieval of medication, exceeding the maximum permitted amount of medication (dosing limit) or the like, and/or if the vital signs of the user/patient are outside of predetermined limits. Alternatively or in addition, such a message can be provided by the user/patient actively pressing an “emergency button”. In some embodiments, a "safe" state of the nasal applicator is provided. This is given in particular in the "off" state. In the “safe” state, the system will not deliver a dose under any circumstance. In some embodiments, the nasal applicator includes patient monitoring sensors. The sensors are suitable for recording patient-specific data. This data can include objective data such as position, movement and/or vital signs (e.g. HR, HRV, SpO₂, blood pressure, electrochemical skin reaction, temperature, photoplethysmogram (PPG), electrocardiogram (ECG), blood pressure trending (BPT), respiratory rate, stress, etc.) or subjective data, collected via patient feedback as described herein. Such monitoring systems can advantageously increase or optimize therapy adherence and thus the therapeutic effect (e.g. through reminders, supporting information, value coupons, etc., status queries, suggestions, activity trackers, notification of relatives/acquaintances, etc.). In some embodiments, it can be provided that the nose applicator is equipped with additional functions, such as reminders, further supporting information, gamification (e.g. collecting points, collecting TV minutes that can be exchanged with the hospital administration for access to the television program, value coupons, etc. ), status queries, suggestions, activity tracker, notification of relatives/acquaintances, participation in surveys, e.g. B. online surveys, etc. to supplement. In some embodiments, the nose applicator can be provided to enable so-called social monitoring and communication, i. H. to provide a means of communication, preferably bi-directional, to family, friends and caregivers, etc. In some embodiments, the nasal applicator can have an antidote in addition to the medical substance in a further substance reservoir, suitable for e.g. B. to reduce or prevent side effects or to avoid an overdose or the like. In some embodiments, the nasal applicator is configured to perform respiratory gas analysis, e.g. g. a capnography, and to display the result of the analysis, for example, to transmit it to a peripheral device and/or to store it in a storage device suitable for this purpose. In some embodiments, the nose applicator can be connected to sensor arrangements and/or evaluation devices, by means of which the position of the user/patient can be recorded and stored. The position can capture the positioning of the patient, whether he/she is standing up, has fallen, and/or the like. These sensor arrays can be provided internally or externally, preferably as detailed herein, for example integrated into smart textiles with integrated sensors. The nasal applicator can also have suitable actuators etc. for this purpose. A mobility protocol etc. can be created in this way, for example. In some embodiments, the patient monitoring sensors or parts thereof can be implanted. In other embodiments, it or parts thereof can be integrated into a dental crown or splint or into an earring or ear clip. In some embodiments, the patient monitoring sensors or parts thereof, sensitivities or states of the user / patient, such. B. pain, detect or make measurable. This can be determined via body reactions such as skin electroplating, blood pressure change, heart rate change and/or pupil dilation. In some embodiments, the nasal applicator includes a nasal applicator locating system. The nasal applicator locating system can be configured to locate the nasal applicator, to locate the substance and/or to locate the user/patient. An integrated real-time (real-time) positioning system z. B. fleet management or the like using wireless connectivity (e.g. via Wi-Fi, Bluetooth, WLAN, GPS, GSM, GPRS, Starlink, WPAN, infrared, RFID, NFC, barcode, QR code, ZigBee, Wibree, WiMAX and/or IrDA etc.) are used. The nasal applicator location system advantageously serves the purpose of facilitating device management and increasing patient safety. In some embodiments, setting up virtual zones or areas can simplify the position determination. In some embodiments, the nasal applicator includes an anti-abuse system and/or an anti-theft system. In some embodiments, the housing of the nasal applicator is designed to be inaccessible, such that access to the or each substance is prevented. This can be realized, for example, by means of a disposable housing that would be destroyed when opened. In some embodiments, the nasal applicator includes a device for physically fixing it. This can be done, for example, using a Kensington^® Castle, a security cable or rope, cable lock, etc. be configured. In some embodiments, common conductors can be provided for data transmission and/or power transmission. For example, a LAN cable for data transmission and/or power (POE) with an integrated steel cable is mentioned here. In some embodiments, the nasal applicator is provided with a predetermined geofence. In these embodiments, the present invention encompasses the possibility of influencing the functionality of the nasal applicator outside of a predefined area, for example by preventing triggering or by neutralizing the active substance of the substance. This can be realized using a software solution and/or wireless connectivity. As already explained here, peripheral devices can serve as a radio cell. In some embodiments, the nasal applicator can be designed to be childproof. The childproofing can be implemented, for example, by means of hardware (e.g. cover, lock and/or safe) and/or by means of software (e.g. patient authentication etc.). In some embodiments, peripheral devices of the nasal applicator can be provided with a safety lock and/or protection against manipulation, e.g. B. a bracelet with inserted steel wire, Kevlar, etc.), in particular, peripheral devices can be infinitely adjustable and thus be individually adjustable to the user / patient. In some embodiments, real-time location (real-time), in particular geofencing, for fleet management and/or locking/unlocking the Serve nasal applicator and / or to trigger a neutralization of the active ingredient in the substance. In some embodiments, the active ingredient in the substance, for example, by a liquid and / or solid and / or gaseous additive, such as. B. a base, acid, antagonist, plaster of paris, cement and/or cold (N₂O ≙ -89°C or CO₂ ≙ -78.5° C) etc. are neutralized or destroyed. In some embodiments, a desiccant, for example as disclosed herein, may be provided for the substance to pass therethrough, wherein the desiccant thereby binds the substance or a material or agent (e.g., a salt) contained therein. As a drying agent z. B. come into question: - sodium sulfate - calcium sulfate - calcium chloride In some embodiments, a filter is provided through which the substance can pass, z. B. designed as a molecular sieve, filter fleece, ion exchanger, or the like. In some embodiments, the nasal applicator may be configured to be reprocessed between treatments for two different patients, for example. A reprocessing can e.g. B. programming or reprogramming, (re)charging or replacing batteries or other energy storage devices as described herein, (re)filling of the or the Be substance reservoirs and / or insert a new cartridge or include. Furthermore, the reprocessing can be or include checking, for example in the form of a system check, complete or partial disposal of the nasal applicator and/or substance, hygiene measures such as cleaning and/or disinfecting, and/or maintenance, which can also include a system update . The controller may optionally be programmed to perform reprocessing steps such as B. to delete the deletion of patient data automatically or on request, such as after selecting a corresponding menu item in the control menu of the storage device. In some embodiments, the nasal applicator is a completely disposable product which, according to applicable regulations, must be completely disposed of after it has been used on the patient for the first time. The nasal applicator, the substance(s) and/or any peripheral device may have to be disposed of individually. In some embodiments, the nasal applicator is partially disposable and includes, for example, reusable electronics, disposable components that have come into contact with the substance and/or the user/patient (e.g., a disposable electronics housing, a disposable nasal tip, a disposable pump, or In some embodiments, the nasal applicator can be configured to include automated and/or logged disposal of the residual amount of the substance. This can be done, for example, by pumping into hazardous waste or into a special container or separate container for medication disposal, suction and neutralization, Etc. respectively. In certain embodiments, this can serve to document the disposal of medication. In some embodiments, the nose applicator includes a modular, preferably expandable, docking station for the electronic control device and/or other peripheral devices. For example, the docking station may be configured to charge the energy storage device, push software updates to the nasal applicator and/or peripherals, pair any two devices included in the nasal applicator, perform hardware verification, implement enables on the nasal applicator/peripheral, etc . In some embodiments, the nasal applicator is configured to automatically (re)order the substance(s). In some embodiments, the protective cap of the nasal applicator contains antibacterial agents to keep the nasal tip clean. In some embodiments, the nasal applicator includes a rinsing device for the nasal attachment, since otherwise the volume of substance in the nasal attachment would "stand still" until the next triggering, which could promote colonization with microorganisms. This can preferably be provided in the substance in the case of sensitive active ingredients. In some embodiments, a priming process may be provided during which e.g. B. the substance is returned to the substance reservoir and automatically collected will. In some embodiments it can be provided that the nasal applicator blocks a triggering if the priming process is not completed. In some embodiments, an audible signal may be emitted during the priming process. This signal can be a warning tone that sounds, for example, as long as the priming process is not completed. Likewise, an acoustic signal, e.g. B. as set forth herein. If an acoustic signal is mentioned here, and in particular above, this should not mislead one from the fact that an optical signal can also be provided, in particular in accordance with the explanations for the acoustic signal. An optical signal can indicate that the priming process is not yet complete. Alternatively or additionally, an optical signal can indicate that the priming process is now, or only now, considered to be complete. In some embodiments, data evaluation via software (e.g. data export, dashboard, reports, e-mails, notifications, screen, app, etc.) can be provided inside and/or outside of the nasal applicator. In some embodiments, the data evaluation can provide for data encryption to be used. This can be or include an encryption key, blockchain, password, passphrase, token, biometrics and/or dongle, etc., for example. In some embodiments of the nasal applicator, further functionalities can be switched on, for example a dashboard (control center) from which the devices of the nasal applicator can be controlled, monitored, etc. centrally, for therapy and/or further devices and/or the application of further substances and/or functions patient management and/or the like. In some embodiments, the nasal applicator may be provided or programmed to conduct internal and/or external surveys, e.g. B. patient satisfaction, side effects or the like. These surveys can be standardized, for example according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10, EU) or according to Diagnosis Related Groups (DGRG) and/or according to the Quality Improvement in Postoperative Pain Therapy (QUIPS)(Germany) and or according to the Risk Evaluation and Mitigation Strategies (REMS) programs, the DEA monitoring programs or the DEA documentation (USA). In some embodiments, the nasal applicator includes a QIUPS interface (questionnaire, information material, etc.) for determining the user/patient's acute and chronic pain perception. In some embodiments, the nasal applicator includes patient education (online and/or offline) for training and/or aftercare of the user/patient, or an opportunity to do so. This can be done, for example, by means of an online video consultation, using a virtual assistant, using instructions for use, a package leaflet, information on side effects, FAQs, Operations and/or product information, forms, surveys, therapy diaries, electronic patient records, etc. In some embodiments, the nasal applicator includes a training function (online and/or offline) for doctors and/or nursing staff, e.g. B. by means of reminders, new training courses, studies, device updates, new functionalities, substances, etc. In some embodiments, customized reports can be created using the present invention to meet the unique needs of hospitals or other facilities and/or regulations. This can include, for example, the regulations of the Food and Drug Administration (FDA) in the USA, the regulations of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany or the regulations of the European Medicines Agency (EMA) in Europe, etc . In some embodiments, the nose applicator is intended to support IoT (Internet of Things), for example by means of healthcare tracking, identification/authentication, data collection/data mining and/or sensing. Data can then be transmitted over the network by means of communication devices suitable for this purpose, in particular without human intervention. To this end, provision can optionally be made to provide one or more of the individual devices and/or peripheral devices of the nasal applicator with unique identifiers so that the individual devices and peripheral devices can recognize one another in a network. In some of the embodiments, one of the peripheral devices is programmed to receive first data from a first of the nasal applicators, process it, and based on the result of the processing create second data and the latter to a second of the nasal applicators and/or to the first Send nasal applicator. In this case, second data z. B. an algorithm, or results obtained when running the algorithm. In this way, in particular, experience gained from using the specific, first nasal applicator on a first user and which can be reflected in the first data can be advantageously used to improve the later use of this first nasal applicator. For this purpose, second data can be created and z. B. be transferred from this peripheral device to the first nasal applicator, which is encompassed by the present invention. Second data can be assignments of the specific first user to a group of users, ie z. B. for its classification or for the classification of its clinical picture or its user behavior. They can exist and be transmitted as formulas, algorithms or in any other form. You can opt out of a pure update, which does not consider the specific user, his behavior and/or his characterization as a patient, but e.g. B. as a medically indistinguishable consumer. In this way, in particular, experience gained from using the specific, first nasal applicator on a first user and which can be reflected in the first data can be advantageously used to improve the later use of a second nasal applicator. For this purpose, second data can be created and z. B. be transferred from this peripheral device to a second nasal applicator, which is encompassed by the present invention. Second data can be as stated above. You can serve the user of the second nasal applicator, experiences which z. B. or etc. gained through the use of the first nasal applicator by the first user, for his future use of his second nasal applicator to his advantage. In some embodiments it is provided that the use of a nasal applicator initially starts with a “basic algorithm”. The initial algorithm, also called the "basic algorithm" here, optionally starts with a preset model and parameter set for the corresponding indication, which can be determined using e.g. B. of age, co-medication, significant previous illnesses, etc. can be initially adjusted. After the start of the treatment or use, the "basic algorithm" (model and/or parameters) is based on the applied doses and/or the resulting concentrations and preferably with the help of the comparison between theoretically calculated next application times and the actual next ones Application times, the activity behavior of the user and / or the input of vital signs trained to characterize the patient. Based on this, the use or treatment of this patient can be optimized with further use of his nasal applicator. For this purpose, procedures, methods and technologies of artificial intelligence and/or machine learning (or the special case of machine learning, deep learning) can be applied in order to train the "basic algorithm" (model and/or parameters), which, for example, can take place on the peripheral device, for example using data that can have been obtained from a large number of uses of different nasal applicators. The treatment data generated in this way (doses applied, times of application, vital signs, etc.) or the "training development" of the "basic algorithm" (model and/or parameters) of each individual user can be collected in a structured manner and homogenized at the end of the therapy or in real time collected in appropriate databases. This database can then be analyzed with the help of "Big Data" analysis methods (e.g. cluster analysis, data mining, curve analysis, pattern analysis, etc.) and/or procedures, methods and technologies of artificial intelligence and/or machine learning (or the special case of machine learning, deep learning) are searched for similarities, patterns, abnormalities, etc. with the aim of deriving or evaluating meaningful and implementable improvements/insights for the "basic algorithm" and implementing them by transferring second data. In an optional step, the "own" database can be combined with other databases, such as e.g. B. Long-term patient data e.g. B. EHR (electronic health record), EMR (electronic medical record) and / or HIS (healthcare information system) and / or gene databases and / or the combination of genotype with phenotypes and / or clinical studies and / or long-term studies z. B. QUIPS (quality improvement in postoperative pain therapy), pain-out, etc. and/or "wearables & sensors" data and/or other computer models such as e.g. B. in silico medicine computer simulations and / or other sources are networked. The aim of this networking is to increase or expand the data situation/basis (amount) for the "Big Data" analysis methods or the AI methods and the resulting results with which the "basic algorithm" is then "trained". . The aim is to then use the "trained new basic algorithm" for future treatments. It can be used as second data and transmitted accordingly. Alternatively or in addition, second data can be generated on the peripheral device based on such a “trained new basic algorithm” and transmitted to a nose applicator. This process can be customized for each indication. In some embodiments, the nose attachment of the nasal applicator can be configured to measure temperature, humidity, airflow, negative pressure, and so on. In some embodiments of the nasal applicator, it can be configured to record the sleep rhythm and, based on this record, to adjust the further dosing (dosing schedule) before/during/after sleep, etc. In some embodiments of the nasal applicator, its housing surface can have a beading effect (lotus effect), i. H. it can be self-cleaning, antibacterial, etc. In some embodiments of the nasal applicator, the housing of the nasal applicator can be coolable, e.g. B. for insulin. A cooling device can be provided, as well as thermally insulating materials or provisions. In certain embodiments of the nasal applicator, the housing of the nasal applicator can be heatable in order to prevent the active substance from freezing, flocculating or degenerating. A heating device can be provided, as well as heat-insulating materials or provisions. In some embodiments of the nasal applicator, the housing of the nasal applicator can have insulation against cold, heat, moisture and/or liquid. In some embodiments of the nose applicator, additional modules can be clicked on. Appropriate holders, devices, etc. can be present on the nasal applicator. In some embodiments of the nose applicator, it can be connected to a smartphone, in particular to the smartphone of the user/patient, via the AUX or Lightning socket. In these embodiments, the smartphone represents the electronics and the corresponding app represents the necessary software for the nasal applicator. It applies here that in addition to wire-based signal transmission, e.g. B. “wired”, also a “wireless” variant, ie a wireless variant, is covered by the present invention whenever signal transmission is disclosed herein. In certain embodiments, the nasal applicator and/or one of the peripheral devices are programmed to be able to emit a position signal, a stand-up signal, a fall signal, etc. For this purpose, accessories such. B. Smartwatches, stowable and / or bondable sensors and textiles or smart textiles with integrated sensors, actuators, haptics, etc., mobility protocol, etc. can be provided. The nasal applicator and/or one of the peripheral devices can be provided and configured to perform these functionalities. They can be used to send a signal to third parties (e.g. to a control center, to the ward room, etc. after a fall of the user), but they can also be used to predetermine the height of one or more subsequent application doses. For example, provision can be made to make the delivery of an application dose and/or the amount dependent on the user standing up in the meantime, ie z. B. has at least left the bed for fewer steps or some physical activity. In some embodiments, the nasal applicator is configured to itself, in particular automatically, mix a concentration of the substance and/or fill the internal substance reservoir and/or dilute it with a substance from a second substance reservoir, e.g. B. Dilute 100 µg/100 µL to 50 µg/100 µL. In some embodiments, the nasal applicator is suitable for energy harvesting, i. H. for energy production e.g. B. by one or more rotation (s) on the case back. A hybrid system between mechanical and electronic systems can thus be created, with the required energy being generated as required. In some embodiments, the control device of the nasal applicator is further programmed, when predetermining the level of the next application dose D_n the specified target concentration C_ED or its minimum value and/or the determined individual concentration curve over time, in particular the determined individual PK curve PK_ind, to consider. In some embodiments, the control device is further programmed, when predetermining the level of the next application dose D_n the specified target concentration C_ED or its minimum value and/or the determined individual concentration curve over time, in particular the determined individual PK curve PK_ind, to consider. In some embodiments, the control device is further programmed to limit the level of the next application dose D_n and/or the resulting concentration; to limit the cumulative amount of all application doses D delivered within a predetermined period of time₀, D₁, D₂, …, D_n-1, D_n, D_n+1, … and/or the resulting concentrations; and/or to limit the cumulative amount of all delivered application doses D₀, D₁, D₂, …, D_n-1, D_n, D_n+1, … the ones from it resulting concentration, the control device optionally accessing data relating to the substance stored in the data memory. In some embodiments, one of the peripheral devices is programmed to receive first data from a first of the nasal applicators, process the same, and send second data to a second of the nasal applicators based on the result of the processing. In some embodiments, one of the peripheral devices is programmed to receive first data from a first of the nasal applicators, process the same, and send second data to the first nasal applicator based on the result of the processing. One or more of the advantages set forth herein may be achievable by some embodiments of the present invention, including the following: Drug therapy is complicated by the fact that patients respond very differently to the same dose of the same substance. There are differences in effectiveness, as well as in the spectrum and severity of undesirable effects and side effects. A significant proportion of the inter-individual variability (i.e. differences between different patients) of individual drugs can be attributed to the patient's genetic make-up (pharmacogenetics). An identical dosage in different patients leads to very different concentration-time curves (pharmacokinetics) and thus to very different ones Effects (pharmacodynamics) and therefore dose individualization is advantageous. In addition to the inter-individual variability, the intra-individual variability d. H. Consider differences in a single patient in drug therapy. The present invention can contribute to this. The cumulative effect (accumulation or enrichment of the substance) through the administration of several consecutive application doses must be taken into account, particularly in the case of multiple administration of substances with a narrow therapeutic index, long elimination phase and side effects. The present invention can allow application of one or more such application doses to be carried out by the user himself, which is safe for the user. The latter applies in particular to older people, for whom a correct or individually adapted dosage plays a decisive role. The present invention can contribute to this. The careful "titration" (which takes place in a determination or finding phase) to a substance concentration and the adjustment of the different application doses or the therapeutic effect while avoiding "overshooting" and the associated avoidance of undesirable side effects can represent a further advantage. For this purpose, the rules on the target concentration (C_ED) be beneficial. In the case of pain therapy, reaching the target concentration represents a state in which the patient is satisfied with his pain therapy. A concentration that exceeds the target concentration no longer contributes to the therapeutic effect, but only increases the side effects to be avoided. The present invention can allow application-related problems of nasal applicators, such as the different nasal anatomy, the nasal condition, the application angle, how deep the individual user usually inserts the nasal attachment and the like, to fix: a preset level of the application dose, its effect in the body of the aforementioned and other factors, according to the invention is not necessary. The present invention is suitable for dealing with such, above all inter-individual, peculiarities when predetermining the level of the application doses. In this way, the desired therapeutic effect can be assured. If the substance, as also encompassed by the invention, is applied nasally, ie non-invasively, the disadvantages of other forms of application can be avoided. In the case of oral administration, for example, the substance must first be metabolized via the liver (first-pass effect) before it can develop its effect. Other disadvantages are the relatively slow onset of action and the difficulty in administering individual doses. Symptoms such as dysphagia and dry mouth make oral administration more difficult. In the case of sublingual administration, for example, the relatively small absorption area and accidental swallowing are problematic. The effect is also affected by drinking, eating or talking too soon after sublingual application. Intranasal administration by means of the nasal applicator according to the invention is painless, easy to self-administer and has a rapid effect. The substance-related blocking of further applications during a blocking period, which is also variable and can be set according to the invention by the blocking device in terms of start and duration, can allow the target concentration to be found early and can advantageously prevent an excessive administration of the substance. The locking device ensures that the applied dose can establish its full effect and the effect can thus be evaluated by the user. According to the invention is thus advantageous u. proposed a self-regulating system which, after a "titration phase" (which is a determination or finding phase) based on application doses that have already been dispensed, the user's actuation behavior and the past time intervals, individualized or personalized application doses, in the case of multiple dosing, are determined and dispensed, which The user's needs, according to or effecting the desired therapeutic effect, corresponds. According to the invention, the user's body is used as a control loop or controlled system, since only the user's body reflects what the substance does to the body (pharmacodynamics) and the respective application dose is determined and applied individually to the user on request/need. According to the invention, using the properties of the pharmacokinetics, the user can be categorized and the course of the concentration in the body over time can be tracked. After an initial "titration phase" you can assign the corresponding user whether he is within e.g. B. the group of pharmacokinetics tends towards the mean or “-SD” or “+SD” and/or define its individual concentration-time curve. Since the target concentration at which the desired therapeutic effect occurs can also be determined according to the invention, the present invention advantageously contributes to the further development of personalized medicine. Inter-individual variability (e.g. age, previous illnesses, consumption of medication) and intra-individual variability (e.g. manipulation, mobilization, circadian course, improvement in the state of illness or state of recovery) can advantageously be taken into account by the control device. Advantageously, there is no need for the doctor or other authorized personnel to intervene, which saves time and resources. Finally, the present invention can contribute to the fact that a smaller amount of substance is advantageously required to achieve the same effect. "Intercepting" the remaining medication, e.g. B. from the OP, which may have been delivered as an initial or initial dose, is also advantageously possible according to the invention. The invention is described below using exemplary embodiments thereof with reference to the attached drawing. The following applies to the figures: FIG. 1 shows a nasal applicator as an example of a medication application device of a first exemplary embodiment, as well as a system according to the invention; 2 shows, schematically and by way of example, a possible course of use over time of the nasal applicator according to the invention as an example of a medication application device; 3 shows, schematically and by way of example, the level of accumulated doses of different applications of a substance to the user; 4 shows, schematically and by way of example, the result of a predetermination of the level of the various application doses; 5a schematically shows the determination of an individual concentration profile for an observed user of the nasal applicator according to the invention using three concentration profiles selected as examples; FIG. 5b shows a continuation of the idea of FIG. 5a on which the invention is based in some embodiments; and 6 shows a nasal applicator of another exemplary embodiment. 1 shows a nasal applicator 100 of a first exemplary embodiment in a schematically simplified representation. As FIG. 1 shows, the nasal applicator 100 has a housing 2 in or on which optionally one, all or more of the devices or components mentioned below can be arranged independently of one another. In other embodiments, one or more of these components can also be present externally, ie not inside the housing 2, in any combination. The nasal applicator 100 has a retrieval device 1 which the user has to actuate in order to be able to apply a dose D (see FIG. 2 or 3) of a substance S from a substance reservoir R. Substance S can be a medicinal or non-medicinal active substance, in particular a painkiller. At the same time, the retrieval device 1 can be or have an optionally provided feedback device 8 . The feedback device 8, if present, can alternatively be a stand-alone device. If the user has actuated the retrieval device 1, which can be a switch, a button, a slot or the like, and thus triggered an actuation signal, a dispensing dispenser 3 can release a quantity of the substance S that it has dosed, i.e. determined in terms of quantity or volume. It can be injected from the substance reservoir R via the lumen of a nasal attachment 4 to be inserted into a nostril (into the nose of the Flow user, inject or the like. Alternatively, it can be applied into the nose from the substance reservoir R via a droplet generator, which can be part of the nasal attachment 4 or another device of the nasal applicator 100 . A, in particular optical or haptic, display 12, z. B. display, LED, etc. can be provided. In addition or in addition to a visual display, an acoustic alarm such as a speaker, buzzer, beeper, a haptic alarm z. B. be provided by vibration, or the like. For this purpose, the substance reservoir R can optionally be acted upon by means of an energy application mechanism or another dispensing device, see e.g. B. Fig. 6, are acted upon. This can act by means of pressure, force, speed, oscillation, vibration, rotation, electrical/magnetic forces, etc. The latter forces or physical events can e.g. B. the triggering speed, the force, the pressure, the acceleration, the flow rate and thus the parameters of the dispensing device, z. B. a droplet generator, influence, i.e. influence the result of the droplet generator. The droplet generator, which can for example be part of the dispensing dispenser 3 or the nosepiece 4, can thus be, for example, a pressurization mechanism acting on the substance S; e.g. B. pushes a piston into the substance reservoir R, or a pump pulls out of the substance reservoir R and applies pressure, force, speed, etc. to the substance S and pushes it through the droplet generator. The optional droplet generator can function mechanically and/or electrically. He can e.g. B. be designed as a nozzle, evaporator, piezo element, etc., or have the like. It can preferably produce a spray or a cloud of droplets or a cloud of particles. If such a release by the dispensing dispenser 3 is not possible at any time and not due to each actuation of the retrieval device 1 and/or not at any time, a blocking device 5 can optionally be provided. It is preferably configured to enable, preferably in a time-controlled manner, a release or delivery by means of the delivery doser 3 during a blocking period defined according to predetermined criteria with regard to its duration and/or the time of its beginning and/or end (see e.g. T_vain_n in Fig. 2) to prevent, disallow, etc., even if the retrieval device 1 should be operated during the lock-up period. During the blocking period, which is of fixed or unchangeable duration in some embodiments, while it is variable or changeable in others, an actuation of the retrieval device 1 does not lead in principle or generally to an application, whereas this does not have to be the case for an actuation after the blocking period has expired or not applicable. The amount or volume of that part of substance S which is contained in individual starting or application doses (D₀, D₁, D₂,…, D_n, ... in Fig. 2 or in Fig. 3) as explained below, at different delivery times tA₀, ta₁, ta₂, …, tA_n, ... is and/or has been delivered can be detected by means of an optional dose detection device 7 . The dose detection device 7 can be configured to be able to measure the individual starting or application doses D₀, D₁, D₂,…, D_n, ..., which were delivered with the nasal applicator 100 and which are variable, i.e. not fixed dose amounts, to measure, determine, store, add up, etc. The dose detection device 7 can, for example, measure an amount, a volume or another parameter which has an immediate Statement about the respective application dose allowed. The dose detection device 7 can additionally or alternatively measure or determine a parameter that allows an indirect statement about the respective application dose, such as a flow per time, a number of strokes of a pump, a number of revolutions of a pump, or the like. The dose detection device 7 or another device such as the electronic control device 9 may be configured, e.g. B. the trigger parameters such. B. to record the speed, the acceleration, the force, the path, etc. Such recorded or determined values are optionally stored. Dose limits and/or concentration limits, which one, e.g. B. based on a unit of time limited or predetermined, limit total dose and / or total concentration can optionally be provided. The dose detection device 7 can, if present, additionally or alternatively be programmed to record a point in time at which one or more specific application doses were or are being administered by means of the nasal applicator 100 . the Dose detection device 7 can additionally or alternatively be programmed to detect a period of time, for example between two or more dispensing times tA₀, ta₁, ta₂,…, ta_n, ... (see Fig. 2 or Fig. 3) administered starting or application doses D₀, D₁, D₂,…, D_n, …. Other lengths of time between any of the times mentioned herein may also be captured (such as tA₁ –/"minus" T_vain_{1_E}, ta₁ – (especially last) tB_{_v}, tB_{1_v1} – ta₀, tB__v (especially the last one, i.e. tB_{_v-1}) – tA₀, T_vain_{1_E} - last tB_{_v}, T_vain_{1_E} – tB_{1_v1}, whose parameters are explained below. An electronic control device 9 can optionally be provided in order to control, regulate and/or monitor the function of the nasal applicator 100 or some, any or all of the devices or components mentioned with reference to FIG. 1 . As stated above, it can be provided in the housing 2 or outside. It can, purely by way of example, be recipients of information about initial or application doses D₀, D₁, D₂,…, D_n, ..., that have been externally predetermined. Corresponding wired or wireless signal connections can be provided, unidirectionally or bidirectionally or multidirectionally, between the control device 9 and the component or components of the nose applicator 100 . An optional detection device 11 can be provided in order to detect whether and/or when the user, who may be a user, operator or patient herein, attempted or initiated a further application dose by actuating the retrieval device 1 . The substance reservoir R can be optionally exchangeable in each embodiment, for example as a single-shot reservoir, as a substance reservoir with sufficient substance S for a large number of application processes, etc. The substance reservoir R can, for example, be pre-filled, self-fillable, integrated, exchangeable, for one-off Application and / or be designed for multiple applications. The substance reservoir R can be arranged inside the housing 2 or externally thereto. Substance S can have any physical state (liquid, gaseous, solid, etc.). An optional data memory M for storing data, or with data stored therein, can be arranged inside the housing 2 or externally thereto. This data can relate to the previous use of the nasal applicator 100 by the user, as well as information on the times or durations mentioned herein (synonym: time intervals), etc.; they can be the result of an evaluation by the control device 9, etc. or optionally data for pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data relating to the substance S and/or underlying medical circumstances such as the underlying disease, etc.; they can be substance-related and/or specified by the doctor or other authorized persons, e.g. B. a tmax value of substance S, a doctor-corrected, so-called "overruled" t_Max-value, e.g. B. the Time or the end of the time interval after application at or in which the maximum concentration or blood concentration occurs, the half-life, the terminal half-life, a value adjusted by the doctor or other authorized persons, etc. The data can be objective and/or subjective. The data can be objective values (sensor values), e.g. B. Blood sugar level, blood pressure, heart rate, respiratory rate, oxygen saturation, etc. The data can be subjective values (“effect values”) that cannot be measured directly. They are derived from collected values such as e.g. e.g. pain score, sedation score, side effects etc.) and/or measured values (e.g. SpO₂, HR, HRV etc.) The data can be or include the recommended concentration, contraindications, side effects, expiry date and/or package insert, specialist information, patient information, Summary of Product Characteristics (SmPC), assembly instructions, disassembly instructions, operating instructions/operating instructions etc. In addition to pharmacological and/or pharmacokinetic data, the data can optionally include user-related data such as e.g. B. weight, age, gender, BMI, previous illnesses, co-medications, comorbidities, allergies, etc. include. Generally, user and/or treatment history (e.g. data on previous interventions, procedures, diagnoses, medical histories, tests, medications received/prescribed, received anesthetics, muscle relaxants, antiemetics, etc.). Such and other data can help the optional control device 9 to calculate more precise dosages or to increase the safety of the therapy. Such and other data can relate to trigger parameters, e.g. B. those which are required to obtain a defined droplet size distribution. Elicitation parameters may differ depending on the predetermined dose. You can z. B. via the triggering speed of the dispensing device. The optional data memory M can be a hardware memory component, a flash memory or an external data memory, for example arranged in a cloud, in a mobile device or the like and/or via WiFi/Bluetooth etc. with other components of the nose applicator 100 be in signal contact. The blocking device 5 and/or the detection device 11 are preferably electronic, e.g. B. by means of the control device 9 realized components. A timer or timer, such as a clock, may be provided. The individual components, as mentioned above, can fall back on it. By means of the timer can optionally z. B. an absolute time measurement (i.e. based on the correct / real / current time), or a relative time measurement, in which, preferably when Initializing or switching on the nose applicator for the first time, a current time stamp is recorded, by means of which the time can be determined back. In some embodiments, it can be provided to inform the user about the end of the current blocking period, for example optically or acoustically or haptically, for example by means of vibration. Since a number of peripheral devices 101 are indicated in FIG. 1, this figure also shows a system according to the invention. The peripheral devices 101 can have the same design or, at least some of them, can differ from one another. Thus, some of the peripheral devices 101 can be nasal applicators, which are optionally configured like the nasal applicator 100, and/or configured as a docking station, as a server, as a smart device, etc., preferably as described herein. Optionally, some or all of the peripheral devices 101 may or may not communicate with one another or with one another in any combination. 1 indicates that they can all also communicate with the nasal applicator 100, although this is also optional. In some embodiments, only some of the peripheral devices 101 can do this. Furthermore, it can optionally be provided that the nasal applicator 100 and/or the peripheral devices 101 and/or the peripheral devices 101 can communicate externally via the nasal applicator 100 and/or the docking station and/or another peripheral device 101 . The substance reservoir R can be z. B. Luer / lock, pin, needle, spike with or without ventilation, etc. be connected. A filter (e.g. a 22 µm particle filter), e.g. B. from or with activated carbon, plastic fibers, or the like, or a porous membrane (e.g. a Porex^® - Filter) may be provided. This filter can be provided at the outlet of the dosing chamber. More than one filter can be provided. The substance reservoir can have a plug that can move up. This enables a position-independent triggering of the nasal applicator. All materials can be inert or partially inert, e.g. B. from or with silicone, glass, cyclo olefin polymer (COP), cycloolefin copolymers (COC), etc. The substance reservoir can have a pierceable membrane, a screw connection, a plug-in connection, a quick connector, etc. The substance reservoir can have a riser tube . The substance reservoir can, for. B. a pouch bottle, a "bag" (as with infusions) or another container that can collapse and does not require a subsequent flow of air into the container. With such solutions you can Trigger independent of position, i.e. in any spatial orientation of the nasal applicator. Fig. 2 shows schematically and by way of example a possible course of use over time of the nasal applicator 100 according to the invention. If the user actuates the retrieval device 1 in order, for example, to obtain an application dose D_n to apply, it is determined by means of the electronic control device 9 or by means of its detection device 11 whether this point in time at which the user requests this next application dose D_n would like to apply, possibly in a blocking period T_vain that is still ongoing_n falls or not. If this point in time at which the fetching device 1 is actuated falls within the blocked period T_vain_n, then at any rate at this point in time the user will not be given an application dose D_n applied. Such points in time are shown in FIG. 2 with reference to a previous lock time T_vain₁ exemplarily as points in time tB_{1_v1} and tB_{2_v1} with reference to other blocking times, e.g. B. as tB_{1_v2}, emerge and are optionally included in the predetermination. On the other hand, if the time at which the retrieval device 1 is actuated does not fall within the blocking period T_vain_n, but lies after the expiry or end of T_vain_{n_E} the blocking duration T_vain_n as in the example of FIG. 2 based on the actuation time tB_n is shown, then the patient is given a delivery time tA_n designated point in time the next application dose Dn applied. The level of the next application dose D_n becomes at a predetermined time tV referred to herein as next_n defined or predetermined before their application by the electronic control device 9, which may have carried out the corresponding calculations itself or adopted the results of such calculations. Predetermining the level of the next application dose D_n is determined by the nasal applicator 100 or its components mentioned in FIG. 1, such as the control device 9, regardless of whether they are included in the housing 2 of the nasal applicator 100 or are external thereto. The first predetermined time tV_n can, as well as the actuation time tB_n at or before the first delivery time tA_n are, he can thus with the first delivery time tA_n coincide, at least within the scope of what is technically possible, so that between the first predetermination time tV_n and next delivery time tA_n sufficient time to actually predetermine or calculate the level of the next application dose D_n and time remains for the relevant devices or components to respond, to which the predetermined level must be signaled or otherwise communicated prior to application. When predetermining the level of the next application dose D_n, which is an example of the variable dose D, i.e. it is not or not exclusively pre-set in an unchangeable manner for the nasal applicator 100 by a doctor or other authorized persons, manufacturers or the like, data that can be read from the data memory M and/or data that are from the in 1 mentioned Components of the nasal applicator 100 were determined are taken into account. This data preferably already includes a time tB before the successful actuation time_n starting time tA₀, to which the user may have an initial dose of D₀ before delivery of the first application dose D₁ may have been administered, be it by means of the nasal applicator 100 according to the invention, by medical personnel, e.g. B. still in a recovery room postoperatively (post-OP), etc. Furthermore, these data can determine the level of this optional starting dose D₀ include. In the present case it is assumed that an initial dose of D₀ at an initial time tA₀, given to the user. This data preferably includes everyone before the successful actuation time tB_n starting time tA₀, ta₁, ta₂, ta_n-1, for which the user already has an initial or application dose D₀, D₁, D₂, D_n-1 was administered or he had dosed himself. Alternatively or additionally, the time that has elapsed since then and preferably also the respective level of the above-mentioned doses are also included. Considering the planned delivery of the next application dose D_n, these data include, for example, at least the amount of the previous application dose D_n-1 and, optionally, their delivery time tA_n-1 or the time elapsed since then. The predetermination, which at the first predetermination time tV_n occurs, thus results in the level of the next application dose D_n. The height at the next predetermination time tV is determined_n, which after the next actuation time tB_n lies, and is not preset by a doctor or other authorized persons, manufacturers or the like, which can also apply to all or some of the other application doses mentioned herein. Predetermining the next predetermination time tV_n takes place taking into account data read out of the data memory M. After the application of the next application dose D_n is, preferably at the delivery time tA_n the next application D_n, again a blocking period T_vain_n scheduled and/or started. It may be the same length as previous or subsequent suspension periods, or different. The length of each lock period can be predetermined and / or z. B. have been set by the doctor or other authorized persons. When scheduling the next lock period, a logic or algorithm can be followed for which at each predicted time tV_n can be included in the calculation. As can be seen from FIG. 2, what was described above for this figure can be repeated. When predetermining the level of the next but one application dose D_n+1 can now, however, optionally, in addition to the levels and/or the delivery times of the above-mentioned application doses and possibly also the starting dose D₀ then for the first time also the amount and/or the application time tAn of the application dose referred to herein as the next, then but already applied application dose D_n are taken into account, which in the meantime can be recorded as data and also kept in the data memory M. Predetermining the level of the next but one application dose D_n+1, which at the predetermination time tV_n+1 takes place, therefore, the length of the time period between the next but one delivery time tA_n+1 and the next delivery time tA_n as well as the lengths of the periods between the next but one delivery time tA_n+1 and the starting time tA₀ or earlier submission times tA₁, ta₂ lie, take into account. Fig. 3 shows schematically and as an example the applied individual doses D₀, D₁, D₂, …, D_n-1, D_n, D_n+1, ... and the doses of substance S accumulated over time t, their levels and/or release times tA₀, ta₁, ta₂, …, tA_n-1, ta_n, ta_n+1, …etc. can be included in the pre-determination of later application doses. The time axis t and its scaling correspond to that used in FIG. 2 or are to be assumed to be identical. The time tA₁ and the time tA₂ thus correspond to the absolute times tA shown in FIG₁ and ta₂. Fig. 4 describes, schematically and by way of example, the phase in the supply of the user with the substance S, also referred to herein as the “titration phase” (which is a determination or finding phase), in which the target concentration causing the therapeutic effect desired by the user is determined . The amount of the following application doses can then be determined on it and/or an individual, dose or concentration-based treatment plan can be set up in a time-controlled manner. Curves as shown in FIG. 4 or elsewhere herein may be based on e.g. B. the explanations of Dubois, A., Bertrand, J., & Mentré, F. (2011) in "Mathematical expressions of the pharmacokinetic and pharmacodynamic models implemented in the PFIM software." UMR738, INSERM, Paris Diderot University. The control device can be programmed to create such curves and/or to carry out the calculations required for this. The content of that publication is hereby incorporated by reference into the subject matter of the present disclosure as well₁, D₂ and others, each of which is an example for the next application dose D_n, as may be used herein. To predetermine the respective application dose D₁, D₂, and further, in the embodiment discussed here, recourse is had to data from the data memory M, which includes pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data. The data can be models, in particular PK models, as well as PK curves. They are preferably patient-specific. These pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data or models include, in the example in FIG Substance S in the user's body after each applied dose. The curves shown reflect the course over time of the concentration of a specific substance S, which results from the applied dose, and the level of the applied doses. The curves also reflect the processes of absorption, distribution, metabolism and elimination in the body. Such pharmacokinetic models follow statistical distributions z. B. taking into account with mean and standard deviation and are mostly patient-specific, i. H. they can run differently from patient A to patient B, which is why they can also be stored in the data memory M for the different users or user collectives according to different statistical distributions. Since the course of such PK curves depends on the route of administration and the dose, the two PK curves provided with reference symbols in FIG. 4 are once as PK50 for the intranasal administration of 50 μg fentanyl and once as PK25 for the intranasal administration of 25 μg referred to as fentanyl. Pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data, as they can be stored in the data memory M, optionally also include information about the substance S such as t in the example in FIG. 4_Max, which can indicate the point in time at which, after application of a dose D, the highest concentration C(t) in the body, for example in the blood, is present. The duration of t_Max can, at least initially or as a follow-up to a first dose, here the starting dose D₀, can be used as the blocking period. Likewise, the blocking period at t_Max be based on the blocking period e.g. B. is only 90% of tmax, or shorter or longer than t by a number of minutes_Max definitely can becomes, etc. Likewise, values above 100% of t_Max possible, e.g. B. 110% of t_Max, so what after t_Max is if you want to include a delay in which the administered substance gets from the blood to the site of action, or if t_Max 13 minutes, but for practicable reasons the blocking time is limited to e.g. B. 10 minutes is to be set. The electronic control device 9 can therefore be programmed to also read out such data stored in the data memory M relating to the substance S and to use this when predetermining the next application dose D_n of substance S must be taken into account. As shown schematically and as an example in FIG. 4, the user was given the starting point in time tA₀ first a starting dose D₀ of 50 µg intranasal fentanyl. The concentration floods up to a first maximum C_{1 max} on, which is why the end of the blocking period T_vain_{1_E} the first blocking period T_vain₁ is set, whose start of blocking period T_vain_{1_p} to tA₀ lies. If only the starting dose D₀ are applied, the concentration C(t) would decrease over time and, assuming the PK curve PK50 shown in broken lines in FIG. 4, would have halved after about 30 minutes. However, since such a halving obviously does not meet the needs of the user who, at actuation time tB₁ has actuated the retrieval device 1, at the first delivery time tA₁ a first application dose D₁ administered in the amount of, for example, 25 micrograms of fentanyl. Predetermining this level at the predetermination time tV1 has shown that 25 µg Given the shape of the PK50 curve, fentanyl suffices in the interplay between decreasing effect or concentration of the starting dose D₀ with simultaneously increasing effect or concentration of the first application dose D₁ a concentration can be achieved which, on the one hand, does not exceed the initial dose D₀ of 50 µg fentanyl and, on the other hand, not below a concentration C that produces the desired therapeutic effect_ED of about 45 µg fentanyl. The concentration C that produces the therapeutic effect desired by the user_ED of about 45 μg fentanyl, the control device 9 recognizes that the user from the actuation time tB₁, which is only shortly before the first delivery time tA₁ lies, has obviously missed the desired therapeutic effect, which has brought him to operate the retrieval device 1. As shown in Figure 4, during the lockout period the user tries T_vain₁ to request two further applications (at times tB_{1_v1} and tB_{2_v1}), since the desired therapeutic effect has apparently not occurred or has not yet occurred. These applications are refused because the concentration of the initial dose of D₀ has not yet reached its maximum, but in any case the blocking period T_vain₁ is not finished yet. It only reaches its maximum towards the end of the blocking period T_vain_{1_E} reach. Since you can now see that the actuation time tB₁ only some time after the end of the T_vain blocking period_{1_E} occurs, the system can use the PK curve to derive a concentration in which the desired therapeutic effect occurs. In this case, a Starting dose D₀ of 50 µg fentanyl a therapeutic time window of 8 minutes (from minute 7 to minute 15). It can also be seen in FIG. 4 that the concentration for the desired therapeutic effect is already reached at minute 7. This can be seen from the fact that from this point in time no further useless actuation times tB_{m_vn} during the blocking period T_vain₁ take place more. As can be seen, the maximum concentration of the starting dose has D₀ but not yet reached its maximum. You can see the concentration that was lost at the last time tB_{3_v1} prevails, use for verification by comparing this prevailing concentration with the expected time of actuation according to T_vain_{1_E} matches. The concentration C that produces the desired therapeutic effect_ED from the first actuation time tB₁ Knowing this, the control device 9 can determine the level of the first application dose D₁ now determine independently. She can predetermine a level of 25 µg fentanyl, knowing that the decay of concentration C(t) due to the starting dose D₀ and the simultaneous rise in concentration C(t) due to the first application dose D₁ to a second maximum C_{2 max} will lead, which will not be above a therapeutically acceptable maximum. Using the pharmacokinetic models (PK curves), the control device 9 can optionally calculate a time in which the concentration of the dose D₁ will fall below the desired therapeutic effect. In Figure 4 this occurs after another 19 minutes or 34 minutes since tA0. From the above considerations, is the concentration C that produces the desired therapeutic effect_ED and/or the next maximum C_{n max} known, from the knowledge of the point in time at which the concentration C_ED or the next maximum C_{n max} will occur or will be reached, the next blocking period will be calculated. So the blocking period T_vain₁ for example the data memory M in connection with the level of the initial dose D₀ be removed. The End T_vain_{2_E} the following, second blocking period T_vain₂ however, from knowing the time of C_{2 max} are obtained, both can be identical to each other. Alternatively, optionally at the time tA₁, to which the concentration C_ED is reached, the point in time can already be calculated at which the concentration C(t) returns to the concentration C_ED will have sunk. Half of the difference between these two points in time, as well as another proportion thereof (e.g. 40%, 35%, etc.), can be set as the duration of the next blocking period. Alternative approaches are also included. In general, the calculated time for the next drop below C_ED be selected as the blocking period, or shortly before. This would be at 58 minutes from tA in FIG₀ the case. So the controller 9 at tA₂, so here TV₂, the blocking period to the next target concentration C_ED (at minute 58 in Fig. 4). The heights of the other application doses such. B.D₂ (in this exemplary case 25 µg fentanyl each) would follow similar considerations as for D₁ predetermined: they were taking into account the amount of application doses already administered and since their Application elapsed time set; for the second application dose D₂ was checked for a residual concentration, which is based on the initial dose D₀ and the first application dose D₁ is due, turned off, for the third application dose, not shown here, would be based on the residual concentration, which is based on the initial dose D₀, the first application dose D₁ and the second application dose D₂ is due to be turned off or turned off. A residual dose is also determined by the amount of the previous application and the time that has passed since its application. The level of the next application dose D_n can be predetermined in such a way that the concentration in the body, in particular in the blood, of the user only after a predetermined period of time, adjustable z. B. by the doctor or other authorized persons, starting from the delivery time tA_n the next application dose D_n, again to the target concentration C_ED will sink. As shown in FIG. 4, the user actuates at actuation times tB_{1_v1}, tB_{2_v1} and tB_{3_v1} ie during the blocking period T_vain₁, the retrieval device 1. However, since these three operations are within the inhibition period T_vain₁ lie, the user can hereby obtain no application dose D. Nevertheless, the control device 9 registers the three unsuccessful attempts at actuation and the times at which they were actuated. In the example of Fig. 4 they are at minute 2 (tB_{1_v1}) or at minute 4 (tB_{2_v1}) or at minute 7 (tB_{3_v1}), and can optionally be stored in data memory M. If the unsuccessful attempts at actuation are analyzed, for example at what time interval they are from one another, when they stop, etc., then in the first place but sufficiently close to the concentration C desired by the user and producing the intended therapeutic effect_ED recognized or specified. In Fig. 4 feedback times are tF_{1_1}, tF_{1_2}, tF_{1_3} and tF_{1_4} specified. They stand for moments in which the user activates a feedback device 8 in order to indicate by means of feedback that he is satisfied or not satisfied with the effect he felt of the concentration present at the time of the feedback. He can thus z. B. signal that he is currently pain-free, that he would not prefer a higher concentration in the body, etc. In Fig. 4 you can see at the PK50_D0 Curve that you have a "straight line" from about 45 minutes, i.e. the gradient remains constant (pseudo-equilibrium "Lambda"). The elimination half-time is now the time in which the prevailing concentration at minute 45 halves. According to the literature, the elimination half-time of fentanyl ranges from 3 to 12 hours, depending on habituation. FIG. 5a shows an example and a schematic representation of three example PK curves PK50_{D0_+SD}, PK50_{D0_M} and PK50_{D0_-SD} the statistical distribution (mean value and standard deviation) of the possible concentration courses in the body of the user after administration of 50 µg intranasal fentanyl, which were obtained from a sufficiently large population. There may be more than three curves lying between the boundaries shown, i.e. H. the corresponding examination of the collective/population could have resulted in more than just three distinguishable PK curves. All of them, or the models on which they are based, can be stored in the data memory M and/or can be taken into account by the control device 9 . For the sake of simplicity only three PK curves are shown and discussed here. In general, the same high doses of a substance can lead to different concentrations C(t) in the body of the individual patient. This is influenced by various factors, such as pharmacogenetics, intra-individuality, age, weight, gender, previous medication, previous illnesses, etc. Furthermore, different nasal anatomies, the nasal condition, the application angle, how deep the nose attachment is inserted and how the manually triggered nasal spray is operated play a role in the course of the respective PK curve, which influences the concentration C(t) over time in the body. By using population pharmacokinetic models such as the PK curves PK50 shown in Figure 5a_{D0_+SD} (mean plus one standard deviation), PK50_{D0_M} (mean) and PK50_{D0_-SD} (Mean value minus a standard deviation) such differences can be mapped. As can be seen, the same dose of 50 µg intranasal fentanyl leads to three different concentration maxima C for these three curves selected as examples_{1max_-SD}, C_{1max_M} and c_{1max_+SD} marked. A large number of other curves could also be displayed. They would in turn have other concentration maxima. The time to maximum concentration is different for the three shown However, curves and those not shown from the multitude of curves are not, or only marginally so. That at the time when the concentration maximum C_{1max_-SD}, C_{1max_M} and c_{1max_+SD} is reached, orienting end T_vain_{1_E} the blocking period T_vain₁ therefore ends at the same time for each of the three curves of FIG. 5a. Assuming that at time tA₀ the starting dose D₀ (D₀=50 µg) is applied, the control device 9 can use the population pharmacokinetic models to determine the maximum concentrations C_{1max_-SD}, C_{1max_M} and c_{1max_+SD} (and many more) calculate. However, since the time until these maximum concentrations are reached is the same for all variants, control device 9 sets the first blocking period (T_vain₁, see Fig. 5a) for all three PK curves equal to the time until the maximum concentration is reached, which in this case is set to 10 minutes as an example. Reaching the maximum concentration can take place in one area. In the present case of intranasal fentanyl, this is between 10 and 12.8 minutes. Since the increase in concentration in the range from 10 to 12.8 minutes is only very small, the time is rounded off to a practicable amount such as e.g. B. 10 minutes. You could of course also choose 11, 12 or 13 minutes. Thus, if at t_A0 the starting dose D₀ (D₀=50 µg) is applied, the resulting maximum concentration is calculated, the rise time until the maximum concentration C is reached_{1max_-} _SD, C_{1max_M} or c_{1max_+SD} calculates the length of the lock period T_vain₁ (here 10 min) calculated and T_vain_{1_p} and T_vain_{1_E} set. Corresponding to the different courses of the three PK curves PK50_{D0_+SD}, PK50_{D0_M} and PK50_{D0_-SD} one would go first Actuation time tB₁, at which concentration falls below the concentration causing the user the desired therapeutic effect, at which the patient can request it (points in time relating to the patient's actuation, predetermination, etc. are not shown here for reasons of simplification, or they fall on the first dispensing point in time , which can actually be the case in practice) the first application dose D₁ would be obtained, a different concentration C_{ED1_+SD}, C_{ED1_M}, C_{ED1_-SD} calculate (or read off with a view to the PK curves plotted as in FIG. 5a) which causes the desired therapeutic effect in each case. This concentration is also referred to herein as the target concentration or C_ED designated. Their value is based i.a. on the pharmacodynamics. It should be noted that the actuation time tB_n the predetermination time tV_n and/or the delivery time tA₁ can match. So it can z. B. apply: tB₁=tv₁=tA₁. Fig. 5a shows that the concentration C_{ED1_+SD}, C_{ED1_M}, C_{ED1_-SD} already before the delivery time t_A1 as C'_{ED1_+SD}, C'_{ED1_M}, C'_{ED1_-SD} had been present at 5, 6 and 8 min, respectively. This can also be done by means of the missing tB_{_v}’s are derived. The above statements are the basis for an embodiment, which is discussed in relation to FIG. 5b , and in which the nasal applicator 100 takes the actuation behavior of the user into account in a concrete way. If one in Fig. 5b from t_A0 If you draw a line (straight through two points) to the corresponding concentrations C1max_-SD, C1max_M and C1max_+SD, you get three straight lines, each with a different gradient. If you now based of the time intervals considers the increase in concentration, one could already make an assessment of which curve the user could possibly be assigned to, because the PK50_{D0_+SD} Curve has the largest concentration increase and the PK50 in the same time interval_{D0_-SD} curve the slightest. Since the desired therapeutic effect depends on the concentration, an initial assessment can be made. 5b schematically shows the exemplary procedure for determining, selecting and/or defining an individual PK curve PK_ind, which shows the course of the active ingredient concentration of 50 µg intranasal fentanyl of a specific, individual user. It should be noted at this point that the goal when determining an individual concentration profile over time, as used herein, does not always have to be an individual PK curve of the user. It may also be sufficient according to the invention if z. B. on the statistical mean curve PK50_{D0_M} oriented or or limit curves such. B. the curve "mean plus standard deviation" or the curve "mean minus standard deviation" or others and knows which range the user is in. FIG. 5b includes the representation of FIG. 5a, but supplements it from the first delivery time tA₁ to administer a first application dose D₁ in the amount of 30 µg fentanyl, for example. From the first delivery time tA₁ are the PK curves PK30 assumed before this point in time_{D1_+SD}, PK30_{D1_M} and PK30_{D1_-SD} created. Based on the target concentration C determined in Fig. 5b_{ED1_+SD}, C_{ED1_M}, C_{ED1_-SD} the control device 9 or the algorithm determines a large number of possible doses and concentrations C(t) derived therefrom, which allow an assessment/categorization, i.e. when the expected times of the next actuation for retrieving a further application dose would have to occur. In this case the system has set 30 µg and the system accumulates the previous curves and projects from the determined target concentrations C_{ED1_+SD}, C_{ED1_M}, C_{ED1_-SD} the respective curves into the future. It is determined at which point in time the target concentrations C_{ED2_+SD}, C_{ED2_M}, C_{ED2_-SD} should be mathematically undershot again. In the example of Fig. 5b they are with tB_{2_+SD}, tB_{2_M} and tB_{2_-SD} marked. Based on this check, the control device 9 can determine in which area or on which curve the user is located. The user can be better classified via these and other iterations. Three possible cases are considered below: Case 1: When the concentration change in the user's body meets the population pharmacokinetic curve PK30_{D1_M} (mean value), it is a good 24 minutes above the desired therapeutic effect concentration, namely from minute 18 to minute 42. It would only occur at minute 42 at time tB_{2_M} deliver an actuation, which, according to a predetermination, finally leads to a renewed delivery of a (second) application dose D requested by him_{2_M} at the time of application tA_{2_M} leads. Case 2: When the concentration change in the user's body meets the population pharmacokinetic curve PK30_{D1_+SD} (Mean value plus one standard deviation), it is 21 minutes above the desired therapeutic effect concentration, namely from minute 18 to minute 39. He would not be until minute 39 at time tB_{2_+SD} deliver an actuation, which, according to a predetermination, finally leads to a renewed delivery of a (second) application dose D requested by him_{2_+SD} at the time of application tA_{2_+SD} leads. Case 3: When the concentration change in the user's body meets the population pharmacokinetic curve PK30_{D1_-SD} (Mean value minus one standard deviation), it is a good 27 minutes above the desired therapeutic effect concentration, namely from minute 18 to minute 45. It would only occur at minute 45 at time tB_{2_-SD} deliver an actuation, which, according to a predetermination, finally leads to a renewed delivery of a (second) application dose D requested by him_{2_-SD} at the time of application tA_{2_-SD} leads. The control device 9 recognizes from the actuation times tB_{2_+SD}, tB_{2_M}, or tB_{2_-SD} that is, whether the user's individual PK curve is now the PK curve PK30_{D1_+SD}, the PK curve PK30_{D1_M} or the PK curve PK30_{D1_-SD} (or one of the countless other PK curves which the control device 9 can also consider). If the retrieval time is at tA_{2_+SD}, then the PK curve meets PK30_{D1_+SD} to. If the retrieval time is at tA_{2_M}, then the PK curve meets PK30_{D1_M} to. If the retrieval time is at tA_{2_-SD}, then the PK curve meets PK30_{D1_-SD} to. If a first direct association between a time profile and the user under consideration is not possible, the control device 9 nevertheless approaches the goal by means of an exclusion method and categorizes/determines for the specific user on the basis his activity behavior, which concentration course over time or which curve best reflects him. After the “titration phase” (which is a determination or finding phase), which is shown in FIG. 5b and can extend beyond the times shown in FIG. 5b, the user can be categorized or classified. The level of the following application doses can then be determined and/or an individual, dose- or concentration-based treatment plan can be set up in a time-controlled manner. If one follows the above procedure, by postulating one or any number of PK curves as a possible, individual PK curve of the user a priori or as a large number of hypotheses (such as: the PK curve PK30_{D1_+SD} to, or the user is hit by the PK curve PK30_{D1_M} to, or the user is hit by the PK curve PK30_{D1_-} _SD zu) already following a first initial or application dose D₀, D₁, D₂, etc. or to a next application dose D_n in general, the correctness of the applicable hypotheses set up can be checked. This leads to an individual pharmacokinetic model for the user, which can be used as a basis for future application doses. In the example of FIG. 5b, the PK curve becomes PK30_{D1_+SD} at actuation time tB_{2_+SD} as PK curve PK_ind determined and used as a basis for the necessary calculations in future preliminary determinations of application doses. A check that the individual pharmacokinetic model determined in this way actually applies can be carried out in the course of the further treatment and in connection with further application doses D_n, D_n+1, etc. are optional at any time. 6 shows a nasal applicator 100 of another exemplary embodiment. The nasal applicator 100 is shown in FIG. 6 in a sectional illustration or in a partially indicated partial section. Using the retrieval device 1, the user can select a next application dose D_n of substance S. Those components that have not already been explained with reference to FIG. 1 are discussed below. Thus, the nasal applicator 100 has a dispensing dispenser 3, which doses the application dose to be dispensed, ie determines the amount. The dispensing doser is embodied here, for example, as a fitting device 15 which determines the quantity of the application dose to be dispensed by determining how large this quantity will be in each case. In order to separate the desired application dose, the placement device 15 can optionally be pulled back further or less far—seen from a nose attachment 4—along the double arrow, for example automatically or by hand. A dispensing device 17 for—here: actively—dispensing the application dose called up via the connection point 4a or the nose attachment 4 is shown in FIG. B. an electric motor 19, and a spindle 21 is provided. Electric motors, as mentioned herein, z. B. be brushless or have a brush. You can e.g. B. be configured as an internal rotor, external rotor and / or slotless motors. An encoder can be integrated, one can be arranged externally, the same applies to a motor controller. The motor can be a stepping motor in some embodiments, e.g. B. hybrid stepper motor, a flat motor, a hollow shaft motor, a servo motor, an asynchronous motor, a synchronous motor or a traveling wave motor or the like. In some embodiments, the motor can be controlled with an open and/or closed loop control and/or by means of an encoder and/or a controller. Encoders can e.g. B. optical transmitted light encoder or reflective encoder, magnetic encoder or the like. The motor can be or will be controlled via the current consumption. For example, if the engine B. to an end position (up or down) or approaches, the power consumption of the motor increases z. B. from 0.5 A to 1 A. This means that an end position or a stop has been reached. This measured value can therefore also be used to control the motor, i.e. to signal it when it is e.g. B. should switch off. A displacement sensor, a flow sensor, limit switch (microswitch) can optionally be used to control the nasal applicator or its motor. In addition or as an alternative, a time control (e.g. energization over a predetermined period of time) is also covered by the present invention. The motor, or the spindle combination, can, in certain embodiments, have a brake, e.g. B. a magnetic brake, eddy current, spring-loaded brake, a limit switch at the top and / or bottom dead center or end point of the stroke, etc. have. The motor or the motor-spindle combination can alternatively or additionally include a damper, e.g. B. to prevent or improve resonance and noise problems. The nasal applicator 100 of FIG. 6 optionally has a dosing chamber 13 that can be distinguished from the substance reservoir R. It serves to receive the application dose of the substance S stored in the substance reservoir R, for which in particular any configuration disclosed herein can be provided, in order to then release it. In order to be able to dispense the application dose, the dosing chamber 13 must first be filled with it. In the embodiment of FIG. 6, this task is performed by the loading device 15. The dosing chamber 13 can be actuated to carry out a sequence of an intake stroke and an ejection stroke, as described below. Venting the system works identically, except that air is a compressible medium and substance S is an incompressible medium. The system will travel full stroke during deflation and may optionally target other parameter values for velocity, force, pressure and/or acceleration for deflation as after venting and in particular for the dispensing of substance S. When the loading device 15 and/or the dispensing device 17 is moved from the top dead center/end point/starting point/starting point (on the side of the one-way valve 23a) relative to the orientation in Fig. 6 is moved away, a negative pressure is created in the dosing chamber 13. This negative pressure allows substance S to flow from the substance reservoir R into the dosing chamber 13. The stopper 17a in the substance reservoir R is also drawn in by this negative pressure and a collapsible container is thus created (suction cycle). Here, the one-way valve 23a closes and the one-way valve 23b opens. This can be done mechanically, pneumatically, hydraulically, electrically, etc. As an alternative to controlling the valves 23a, 23b by means of negative pressure, the valves 23a, 23b can be controlled electrically. For this purpose, the position of the placement device 15 is used. The valves 23a, 23b can also be designed or operated in any combination of the functions mentioned. To deliver the substance S (delivery cycle) out of the dosing chamber 13, the direction of the loading device 15 is reversed, and it thereby becomes the delivery device 17. This moves with a predetermined speed, force, pressure, acceleration in the direction of the one-way valve 23b . When the path is reversed, an overpressure is created in the dosing chamber 13, which One-way valve 23a closes and one-way valve 23b opens. This allows the substance S to be pushed through the nosepiece 4 via the joint 4a. The valve control can take place as described above. Optionally, other values for speed, force, pressure and/or acceleration are applied or aimed for in the intake cycle than in the discharge cycle. The dosing chamber 13 can be manufactured with high precision in order to cause minimal variability in the dispensing quantity, which can also apply to the loading device 15 and the dispensing device 17 . This can be realized by using a plastic with low shrinkage or low water absorption. Alternatively or additionally, z. B. in Fig. 6, a sleeve may be pressed, which preferably has very narrow tolerances in diameter. This allows the application volume to be better controlled. The application volume results from the formula: volume = area * stroke. The area is that of a circle A=d²*π/4. Plastics with low shrinkage or low water absorption can be referred to as "dimensionally stable plastics". Dimensional stability refers to the ability of polymers to maintain their size under various environmental conditions. A dimensionally stable plastic is therefore less inclined to absorb moisture and shows less thermal expansion. Dimensionally stable plastics include polymers such as PEEK, PPS, PSU, PPSU, PEI and PET. Moisture absorption can not only lead to a change in size, but also to a change in material properties. This can e.g. affect mechanical strength and/or electrical properties such as electrical conductivity and dissipation factor. A polymer without water absorption is z. B.PTFE. The following polymers are plastics with very low water absorption: PEEK, PPS, PSU, PPSU, PEI, PVDF, PET, PPE, PP and PE. A low water absorption is also recorded for POM, PA12, PC and ABS. The metering chamber 13, the dispensing device 17 and / or the loading device 15 can be self-sealing and / or a seal z. B. a sealing ring 16, piston rings, O-rings, sealing lips, etc. have. The dosing chamber 13 and/or any elements that come into contact with the substance, such as the dispensing device 17, the loading device 15 and/or others, can be coated. A possible coating can e.g. B. from parylene and / or consist of inert materials such. As glass and / or engineering plastics such. B. cycloolefin copolymers (COC), cyclo-olefin polymer (COP), etc. Here, as well as in any other embodiments, the dosing chamber 13, the dispensing device 17 and / or the loading device 15 from materials exist or have those that do not need lubrication z. B. POM homopolymer, Teflon, etc. It can also lubricants such. B. silicone oil can be used or coatings with which the friction is reduced. In some embodiments, additives can also be added to the plastics in order to improve the sliding properties, e.g. B. CORDULEN, montan wax, high molecular weight polyethylene wax (PE-LD, PE-HD), fluoroelastomers, etc. In certain embodiments, the dosing chamber 13, the dispensing device 17 and / or the loading device 15 can also consist of other materials such as plastic or such exhibit. As can be seen from the above explanations, the dosing chamber 13 is variable in that the loading device 15 sometimes separates more and sometimes less amounts of substance S from the substance reservoir R, with the space in which the application dose separated in this way is present before it is discharged being defined as dosing chamber 13 can. The substance reservoir R can be clamped, rotated, plugged, fastened or guided in the housing in a guide. The substance reservoir R can be connected to the loading device 15, the dispensing device 17, the nose attachment 4, the dispensing dispenser 3 or the connection point 4a. The connection can be made by means of a flexible or rigid line 22 . The line 22 can be stationary, or with the Discharge device 17 and / or the placement device 15 to be movable. The substance reservoir R can be z. B. Luer / lock, pin, needle, spike with or without ventilation, etc. with the dosing chamber 13 can be connected. To establish a fluid connection between the dosing chamber 13 and the substance reservoir R, a needle 38 can be provided, for example, which z. B. pierces a septum 39 of the vial. A filter, e.g. B. a (e.g. 22 µm) particle filter or a porous membrane (e.g. a Porex^® – Filter), interposed. In some embodiments, this filter can be at the outlet of the dosing chamber 13; a second filter can also be provided there. As will become clear from the following explanations, the loading device 15 can be identical to the dispensing device 17, but it can also be provided separately therefrom. Although the dispensing device 17 and/or the equipping device 15 can have an energy store for mechanical energy or spring energy and/or hydraulic and pneumatic energy as the energy loading mechanism, this is not the case in the embodiment of FIG. 6 . The electrical energy store 20 can be integrated into the dispensing device 17 and/or the equipping device 15 be integrated or be connected to them by means of an external connection. The integrated energy store 20 can be charged for a trip and after each application by means of a charger, z. B. a Qi charging pad, or in a housing shell using a PIN connection. The electrical energy store 20 can be a capacitor or the like. The power can be supplied via power cable, power pack, etc. or via Ethernet (LAN), English Power over Ethernet (PoE). The latter refers to a process with which network-enabled devices can be supplied with power via the eight-wire Ethernet cable. Such supply may be provided herein. In some embodiments, solar cells or mechanisms for energy harvesting can be provided for this as an alternative. In FIG. 6, the dispensing device 17 and/or the loading device 15 are designed as an electric drive, here with an electric motor 19 with a spindle 21, which are coupled. In other embodiments, this coupling can also take place via a gear or be designed with a transmission. Referring to FIG. 6, it should be noted that in some embodiments, such as B. that of Fig. 6, the dispensing device 17 and the loading device 15 can be realized by a common mechanism, where the mechanism z. B., when it moves in a first direction (e.g. away from the connection point 4a), the dosing chamber 13 fills as loading device 15, and when it moves in a second direction, which can be opposite to the first (e.g. towards the connection point 4a) proceeds, the contents of the metering chamber 13 z. B. via the nose piece as a dispensing device 17 deploys. A counter-rotation of spindle 21 and/or motor 19 during suction on the one hand and application on the other hand can be provided, as has already been described elsewhere herein. Alternatively, rotation in the same direction is possible both for filling and for emptying the dosing chamber 13, as described above, e.g. B. performed with reference to the slider crank drive. Likewise, filling and emptying with mutual rotation are possible when using the sliding crank drive, as described above. The dispensing device 17 and/or the fitting device 15 are detachably or non-detachably connected to the spindle 21 and/or the motor 19 . The substance reservoir R, the dispensing device 17 and/or the loading device 15 can be designed as disposable products. The dispensing device 17, the loading device 15 can be designed as a reusable product. Both optionally provided housing shells can be designed as disposable products. The electronic control device 9, the motor 19, the spindle 21 and/or other components can be reusable. The nasal applicator 100 of FIG. 6 also has an optional mechanism for changing the capacity of the dosing chamber 13 . By means of this mechanism, the capacity of the dosing chamber 13 can be varied for a subset of the substance S, which makes it possible to apply doses of different sizes. In some embodiments this mechanism is part of the dispensing meter 3, in others like the present one it is not. The electronic control device 9, see FIG. 1, if provided, can be programmed to move and/or have the dispensing device 17 deployed at a variety of speeds, forces, pressures, accelerations, flow rates. With a motor-driven, nasal device, the problem can be solved that when triggered by hand by pressing, each user applies a different speed, force, pressure, acceleration. It is not guaranteed that every user will have the same speed, e.g. B. tripping speed or the ideal tripping speed is generated. Since the triggering speed has the greatest influence on the droplet size distribution, the spray pattern and the plume geometry, a triggering that is always identical between users is of particular advantage, since in comparison to a manual triggering, a constant spray pattern, in particular the droplet size distribution, the Spray Pattern and Plume Geometry and Application Volume is secured. In this way, it can advantageously be ensured that when the next application dose is applied, the stroke distance required for this, ie the complete stroke, is always covered. For example, if a 5mm path has to be covered for a 150 µL dose, then it can be ensured, as described here, that not only e.g. B. 4mm can be covered, which could be possible with a manual solution based on the pressure strength or depth, but, due to the options described here, the complete required stroke distance is always covered. Additionally or alternatively, the electronic control device 9 can be programmed to act on the mechanism for changing the capacity of the dosing chamber 13 . This can also be done manually and the triggering can still be done automatically. The droplet size distribution, the spray pattern, the plume geometry can preferably be adjusted and optionally adjusted differently for each application rate. Depending on the active substance and its properties, e.g. B. viscosity, surface tension, etc., a different speed, a different force, a different pressure, a different acceleration, a different flow rate may be required. In some embodiments, the device can run its own speed, force, acceleration, flow rate or pressure for each dose amount. This can e.g. B. be or will be set in advance. In certain embodiments, a sensor can determine the location or triggering position, e.g. B. vertically or horizontally (and everything in between), and then adjust the speed, force, pressure, acceleration to this position. In the embodiment of Fig. 6, the loading device 15 has at least one first one-way valve 23a or non-return valve for loading the dosing chamber 13 with the application dose of the substance S and/or the dosing chamber 13 is delimited by at least one first one-way valve 23a or non-return valve . This valve can B. be arranged in a piston itself or at any point, for. B. at any point in the supply line from the substance reservoir R to the dosing chamber 13. The fitting device 15 has in the embodiment of FIG. 6 at least one second one-way valve 23b or check valve. Alternatively z. B. the first valve 23a as a switchable three-way valve and / or executed in a different way. This means that the first valve 23a, as a single element, can also perform the function of two valves. The dosing chamber 13 is delimited here, for example, by at least the second one-way valve 23b or non-return valve. Optionally, the second check valve 23b has an opening direction that is opposite to that of the first check valve 23a in relation to the dosing chamber 13 . Optionally, the function of the first one-way valve 23a and the function of the second one-way valve 23b in a common component, ie z. B. in a valve element, be merged. The dosing chamber 13 can optionally be connected or brought into connection with the atmosphere via a ventilation valve (not shown here). Provision can be made for the initial venting of the system to be operated via such a vent valve and/or to eliminate air bubbles at a later point in time. A filter can be provided at a suitable place. The device optionally consists of two housing parts, namely an upper housing part 2b and a lower housing part 2c, which are separated in FIG. 6 by a housing parting line 2d. In the schematic representation of Fig. 6, the upper housing part 2b contains the substance reservoir R, the dosing chamber 13, the dispensing device 17 and/or the loading device 15. Valves, filters, ventilation, the connection point 4a for the nose attachment 4 etc. can also be in the upper housing part 2b be provided. The lower housing part 2c has the electronic control device 9, the motor 19, the spindle 21, the optional encoder, controller, the brake, the damper, the energy store 20, the retrieval device 1, etc. The components mentioned above are only arranged as an example as shown in FIG. 6 . They can be arranged in any combination. One or both of the housing shells or parts 2b, 2c can be disposable. The nasal applicator 100 can be delivered fully assembled, sterilized, repackaged or delivered. Alternatively, it is only completed on site, at the patient's bedside, by the patient, the doctor, etc. So e.g. B. the substance reservoir R can still be inserted into the upper housing shell and the latter are then assembled with the lower housing shell. The electronic control device 9, the motor 19, the spindle 21, the optional encoder, the controller, the brake, the damper, the energy store 20 and/or the retrieval device 1 can form a unit in any combination with one another. They can be inserted into a lower housing part 2c, which then forms the housing 2 together with the upper housing part 2b. Optionally, the housing shells (upper and lower part) 2b, 2c could be opened and disposed of during disassembly. The electronics can be removed from the lower shell or the lower housing part 2c without touching them. The housing parts 2b, 2c can be used alone or together after the end of the treatment of the user z. B. can also be intentionally destroyed to prevent further use of the nasal applicator. This can be provided, for. B. breaking off an optional snap hook or irreversibly damaging, breaking off, displacing another positive connection, etc. For example, deforming the snap hook, displacing a connecting part or a lock, etc. After treatment, the nasal applicator 100 can be emptied automatically and/or manually and discarded as a whole. Alternatively, it can be broken down into parts and only partially discarded or reprocessed or reused. B. the electronic control device 9, the motor 19, the spindle 21, etc. are suitable. The nasal applicator 100 can include a cover which can be opened to insert the substance reservoir R and/or the electronic control device 9 . A sealing ring 16 can be provided in order to ensure the tightness between loading device 15 and/or dispensing device 17 on the one hand and the surrounding sleeve or shaft on the other hand. A flow sensor 11a can be provided. It can be part of the detection device or represent it. An optional stopper 17a is provided to limit the volume of the substance reservoir R, it can be slidably mounted. An optional spring may be provided in this or any other embodiment which directly or indirectly pushes against the plug 17a to move it out of a position which it may have been in for a prolonged period of storage upon firing of the nasal applicator 100. The valve 23a shown in FIG. 6 can optionally be in any embodiment at, on and/or in the Dispensing device 17 and / or the placement device 15 or in the immediate vicinity. Optionally, in any of the embodiments, the line 22 through which the substance S is guided into the dosing chamber 13 can run through the loading device 15 and/or the dispensing device 17 . In any specific embodiment, the fitting device 15 and/or the dispensing device 17 can optionally have a connection for the line 22 . Optionally, in any of the embodiments, the equipping device 15 and/or the dispensing device 17 can be hollow or continuous. Optionally, in any of the embodiments, the line 22 can move with the equipping device 15 and/or the dispensing device 17 . In other embodiments, the line 22 does not move with the fitting device 15 and/or the dispensing device 17. Optionally, the substance reservoir R can be installed in any embodiment rotated by 180 degrees compared to the illustration in FIG. All components can optionally be positioned as desired in any embodiment in order to avoid blind assembly, i.e. installation without a view, the risk of injury from the needle 38 is reduced and that the Substance reservoir R, which can have the septum 39 or some other connection, can be mounted more easily.

Reference numeral 100 nasal applicator 101 peripheral device 1 retrieval device 2 housing 2b upper housing part 2c lower housing part 2d housing parting line 3 dispensing doser 4 nose attachment 4a connection point 5 locking device 7 dose detection device 8 feedback device 9 electronic control device 11 detection device 11a flow sensor (flow sensor) 12 display 13 dosing chamber 15 loading device 16 seal or sealing ring 17 dispensing device 17a Plug 19 electric motor 20 energy accumulator 21 spindle 22 line 23a first one-way valve, check valve 23b second one-way valve, check valve 38 needle 39 septum C _ED1 Target concentration, concentration required for the desired effect/effect at the time of actuation tB ₁ C _{ED2 Target} concentration, concentration required for the desired effect/effect at the time of actuation tB ₂ C _{ED3 Target} concentration, concentration required for the desired effect/effect at the time of actuation tB ₃ C _{ED1_ +SD} First specified target concentration, concentration on the PK curve PK50 _{D0_M} required for the desired effect/response at the time of actuation tB ₁ C _{ED1_M} First specified target concentration, concentration on the PK curve PK50 _{D0_M} required for the desired effect/response at the time of actuation tB ₁ C _{ED1_-SD} First set target concentration, concentration required for the desired effect/response on the PK curve PK50 _{D0_-SD} at actuation time tB ₁ C _{ED2_+SD} Second set or first estimated target concentration, concentration required for the desired effect/response on of PK curve PK30 _{D1_+SD} at actuation time tB ₂ C _{ED2_M} Second set or first estimated target concentration, concentration required for desired effect/response on PK curve PK30 _{D1_M} at actuation time tB ₂ C _{ED2_-SD} Second set or first estimated target concentration, concentration required for the desired effect/response on PK curve PK30 _{D1_-SD} at actuation time tB ₂ C´ _ED1 First before delivery time tB ₁ determined target concentration, concentration required for the desired effect/effect on the PK curve PK50 _D0 C´ _{ED1_+SD} First target concentration determined before the dispensing time tB ₁ , concentration required for the desired effect/effect on the PK curve PK50 _{D0_+ SD} C´ _{ED1_M} First target concentration determined before delivery time tB ₁ , concentration required for the desired effect/effect on the PK curve PK50 _{D0_M} C´ _{ED1_-SD} First target concentration determined before delivery time tB ₁ , concentration required for the desired effect/effect on the PK curve PK50 _{D0_-SD} C(t) concentration at time t C _nmax concentration maximum C1max First maximum on d he PK curve PK50D0 C _2max Second maximum on the PK curve PK25 _D1 C _3max Third maximum on the PK curve PK25 _D2 C _{1max_+SD} First concentration maximum on the PK curve PK50 _{D0_+SD} C _{1max_M} First concentration maximum on the PK curve PK50 _{D0_M} C _{1max_-SD} First concentration maximum on the PK curve PK50 _{D0_ -SD} C _{2max_+SD} Second concentration maximum on the PK curve PK30 _{D1_+SD} C _{2max_M} Second concentration maximum on the PK curve PK30 _{D1_M} C _{2max_-SD} Second concentration maximum on the PK curve PK30 _{D1_-SD} D dose D ₀ initial dose; Initial dose D ₁ First application dose, preceding application dose D ₂ Second application dose, following application dose D ₃ Third application dose D _n-1 The application dose preceding the next application dose D _n Next application dose D _n+1 The application dose following the next application dose or the one after that M Data memory PK25 PK- Curve for 25 µg fentanyl single dose PK50 PK curve for 50 µg fentanyl single dose PK25 _Dn PK curve for 25 µg fentanyl multiple dose PK50 _Dn PK curve for 50 µg fentanyl multiple dose PK50 _+SD PK curve for 50 µg fentanyl single dose, mean of all observed individuals of the collective plus one Standard deviation of PK50 _M PK curve for a single dose of 50 µg fentanyl, mean value for all individuals in the collective considered PK50 _-SD PK curve for a single dose of 50 µg fentanyl, mean value for all individuals in the collective considered minus one standard deviation PK50 _{Dn_+SD} PK curve for 50 µg fentanyl multiple dose, mean value for all observed individuals of the collective plus one standard deviation PK50 _{Dn_M} PK curve for 50 µg fentanyl multiple dose, mean value for all observed individuals of the collective PK50 _{Dn_-SD} PK curve for 50 µg fentanyl multiple dose, mean value for all observed individuals of the collective minus one standard deviation PK30 _{Dn_+SD} PK curve for 30 µg fentanyl multiple dose, mean value across all individuals of the collective considered plus one standard deviation PK30 _{Dn_M} PK curve for 30 µg fentanyl multiple dose, mean across all considered individuals of the collective PK30 _{Dn_-SD} PK curve for 30 µg fentanyl multiple dose, mean value of all observed individuals of the collective minus one standard deviation PK _Ind Individual PK curve R substance reservoir S medicinal substance T_vain _n suspension periods T_vain _{n_S} start of suspension period T_vain _{n_E} end of suspension period tA ₀ starting time; time of delivery of the starting dose; Initial dose tA ₁ ,…, tA _n , tA _n+1 time of delivery 1 to n+1 tA _{2_+SD} time of delivery Mean value for all individuals of the collective considered plus a standard deviation tA _{2_M time of} delivery Mean value for all individuals of the collective considered tA _{2_-SD} Delivery time Mean value across all observed individuals of the collective minus a standard deviation tB ₁ ,..., tB _n , tB _n+1 Actuation time 1 to n+1 tB _{2_+SD} , tB _{2_M} , tB _{2_-SD} Calculated target concentration time tB _{1_v1} , tB _{2_v1} Futile actuation points during the blocking period T_vain ₁ tB _{1_v2} , tB _{2_v2} Futile actuation points during the blocking period T_vain ₂ tB _{m_vn} Futile actuation points during the blocking period T_vain _n tF _{n_1} First feedback point in time tF _{n_2,} tF _{n_3} Feedback points in time tF _{n_4} Last feedback point in time, ..., tV tV ₁ _n , tV _n+1 Predetermination times 1 to n+1

Claims

Claims 1. nasal applicator (100) for nasally administering at least one medicinal substance (S), in particular an analgesic, with a housing (2) having or connected to - a substance reservoir (R) for holding a quantity of the substance (S); - A retrieval device (1) for actuation by the user with the aim of retrieving a next application dose (D _n ) of the substance (S); - A dispensing dispenser (3) for dispensing application doses (D ₀ , D ₁ , D ₂ , ..., D _n-1 , D _n , D _n+1 , ...) upon actuation of the retrieval device (1) at a respective dispensing time (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 , tA _n , tA _n+1 , ...); - A connection point (4a) for a nose attachment (4), or a nose attachment (4) or a nose piece; and - a dispensing device (17) for dispensing an application dose of the substance (S) via the connection point (4a) or the nasal attachment (4) or the nose piece and/or out of the nasal applicator (100). 2. nasal applicator (100) according to claim 1, further comprising - A dosing chamber (13) for temporarily receiving the application dose of the substance reservoir (R) stored substance (S); and - a loading device (15) for loading the dosing chamber (13) with the application dose of the substance (S) from the substance reservoir (R). 3. Nose applicator (100) according to claim 2, wherein the dispensing device (17) is arranged to dispense the application dose of the substance (S) present in the dosing chamber (13) via the connection point (4a), the nose attachment (4) or the nosepiece and/or out of the nasal applicator (100). 4. nasal applicator (100) according to any one of claims 2 to 3, wherein the dispensing device (17) and / or the loading device (15) has an energy store for mechanical energy or spring energy. 5. nasal applicator (100) according to any one of the preceding claims, wherein the dispensing device (17) and / or the loading device (15) has a motor, preferably an electric motor (19). 6. nasal applicator (100) according to any one of the preceding claims, wherein the dispensing device (17) and / or the loading device (15) has a spindle (21). 7. nasal applicator (100) according to claim 6, wherein the motor is connected to the spindle (21).

8. nasal applicator (100) according to any one of the preceding claims, further comprising - a mechanism for changing the capacity of the metering chamber (13) for the application dose of the substance (S). 9. nasal applicator (100) according to any one of the preceding claims, further comprising - a second fluid chamber, comprising a desiccant or a means for neutralizing the substance. 10. nasal applicator (100) according to any one of the preceding claims, wherein the dispensing device (17) and the loading device (15) have identical components or consist of these. 11. nasal applicator (100) according to any one of the preceding claims, further comprising - an electronic control device (9). 12. Nose applicator (100) according to claim 11, wherein the electronic control device (9) is programmed to allow the deployment device (17) to be moved and/or deployed at a plurality of speeds. 13. nasal applicator (100) according to any one of claims 11 to 12, wherein the electronic control device (9) programmed to act on the mechanism for varying the volumetric capacity of the dosing chamber (13). 14. The nasal applicator (100) according to any one of claims 2 to 13, wherein the loading device (15) for loading the dosing chamber (13) with the application dose of the substance (S) has at least a first one-way valve (23a) or check valve and/or the metering chamber (13) is delimited by at least one first one-way valve (23a) or check valve. 15. The nasal applicator (100) according to any one of claims 2 to 14, wherein the loading device (15) for loading the dosing chamber (13) with the application dose of the substance (S) has at least one second one-way valve (23b) or check valve and/or the dosing chamber (13) is delimited by at least one second one-way valve (23b) or non-return valve, the second non-return valve (23b) preferably having an opposite opening direction in relation to the dosing chamber (13) than the first non-return valve (23a). 16. The nasal applicator (100) according to any one of the preceding claims, further comprising: - a blocking device (5) for temporarily blocking the dispensing dispenser (3) during a period before or after the respective dispensing time (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 , tA _n , tA _n+1 , ...) of the delivered application dose (D ₀ , D ₁ , D ₂ , ..., D _n-1 , D _n , D _n+1 , ...) blocking period (T_vain ₁ , T_vain ₂ , …, T_vain _n-1 , T_vain _n , T_vain _n+1 , …) with one Start of blocking period (T_vain _{1_S} , T_vain _{2_S} , …, T_vain _n- _{1_S} , T_vain _{n_S} , T_vain _{n+1_S} , …) and end of blocking period (T_vain _{1_E} , T_vain _{2_E} , …, T_vain _{n-1_E} , T_vain _{n_E} , T_vain _{n+1_E} , ...); 17. Nasal applicator (100) according to any one of the preceding claims, further comprising: - a dose detection device (7) for detecting the level of the dose by means of the dispensing dispenser (3) at the dispensing time (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 , tA _n , tA _n+1 , ...) each delivered application dose (D ₀ , D ₁ , D ₂ , ..., D _n-1 , D _n , D _n+1 , ...). 18. Nose applicator (100) according to one of the preceding claims, further comprising: - a data memory (M) for storing at least the delivery times (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 ) of one or more already delivered application doses ( D ₀ , D ₁ , D ₂ , ..., D _n-1 ) and/or the heights of these application doses (D ₀ , D ₁ , D ₂ , ..., D _n-1 ). 19. Nose applicator (100) according to one of the preceding claims, further comprising: - a detection device (11) at least for detecting an activation behavior of the user at an activation time (tB _n ) relating to the retrieval device (1) with the aim of a next or further Application dose (D _n ) to apply.

20. Nose applicator (100) according to any one of claims 11 to 19, wherein the electronic control device (9) is further programmed to - read out data stored in the data memory (M); - Evaluation of the means of the detection device (11) detected actuation behavior of the user; - Predetermine, at a predetermination time (tV _n ), the amount of the next or the further application dose (D _n ), which the user in the event that this outside of a blocking period (T_vain _n ) actuates the retrieval device (1), to a next delivery time (tA _n ) can be delivered, the predetermination time (tV _n ) being at or after the actuation time (tB _n ), and the predetermination being carried out taking into account the data read out of the data memory (M), these data being at least a) the delivery time (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 ) of one or more of the already delivered application doses (D ₀ , D ₁ , D ₂ , ..., D _n-1 ), or between the or the several delivery times (tA ₀ , tA ₁ , tA ₂ , ..., tA _n-1 ) of the already delivered application doses (D ₀ , D ₁ , D ₂ , ..., D _n-1 ) and the time after the next actuation time (tB _n ) lying delivery time (tA _n ) elapsed time, on the one hand and / or b) the amount of a or more of the application doses already delivered (D ₀ , D ₁ , D ₂ , ..., D _n-1 ) on the other hand. 21. Nasal applicator (100) according to claim 20, wherein - the data memory (M) further comprises pharmacological, pharmacodynamic, pharmacometric and/or pharmacokinetic data relating to the substance (S) or other data associated with the substance, wherein - the electronic control device (9) further programmed for the additional readout of data stored in the data memory (M) relating to the substance (S) or data associated with the substance, and wherein - the next application dose (D _n ) of the substance (S) is pre-determined taking into account the additionally read out data Data. 22. Nose applicator (100) according to claim 20 or 21, wherein the electronic control device (9) is also programmed to initiate the further steps: - dispensing the next application dose (D _n ) at the predetermined level at the corresponding dispensing time (tA _n ) by means of the dispenser (3); and subsequently - storing the level and/or a concentration of the application dose resulting therefrom the next application dose (D _n ) delivered in the data memory (M) and causing the blocking device (5) to temporarily block the dispensing dispenser (3) for a _blocking period ( _{T_vain} _n+1 ) with a blocking period start (T_vain _{n+1_S} ) and blocking period end (T_vain _{n+1_E} ) and/or storage of the delivery time (tA _n ) of the delivered, next application dose (D _n ) in the data memory (M). 23. Nasal applicator (100) according to claim 22, wherein the electronic control device (9) is further programmed, the sequence of further steps of claim 22 also in connection with one or more of the next application dose (D _n ) following deliveries of further application doses (D _n+1 ) to be executed or caused. 24. nasal applicator (100) according to claim 23, wherein the electronic control device (9) is further programmed to read out data from the data memory (M) which z. B. PK curves (PK25, PK50) and/or models, and which depict a time course between concentration (C(t)) in the body, in particular blood, of the patient, and based on this, a next maximum (C _1max , C _2max , C _nmax ) of the concentration (C(t)). The nasal applicator (100) of claim 24, wherein the electronic controller (9) is further programmed in predetermining the next Application dose (D _n ) based on data stored in the data store (M), in particular PK curves (PK25, PK50) or models, and a therapeutic maximum stored in the data store (M), to determine the level of the next application dose (D _n ) in such a way that the next maximum (C _1max , C _2max , C _nmax ) will not exceed the predetermined maximum. 26. Nose applicator (100) according to one of claims 20 to 25, wherein - the evaluation of the detected actuation behavior of the user, the determination of the actuation time (tB _n ) for retrieving the next application dose (D _n ), or the actuation time (tB _n ) between this and the blocking period end (T_vain _{n_E} ) of the last elapsed blocking period (T_vain _n ) period of time; wherein - the predetermination includes taking into account the determined next actuation time (tB _n ) or the determined period of time. 27. nasal applicator (100) according to any one of claims 9 to 26, further comprising - a feedback device (8) for actuation by the user; the detection device (11) being programmed to detect one in at least one, preferably first feedback time (tF _{n_1} ) occurred actuation of the feedback device (8); wherein the control device (9) is programmed to determine the concentration of the substance (S) present in the body or in the blood of the user at the at least one feedback time (tF _{n_1} ), and to set a target concentration (C _ED ) or its maximum value to a value in each case below the determined concentration. 28. The nasal applicator (100) according to claim 27, wherein the detection device (11) is further programmed to detect at least one actuation of the retrieval device (1) by the user at actuation times (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) and/or to record a, preferably last, feedback time (tF _{n_4} ) after which further actuations of the feedback device (8) by the user are absent, preferably the last non-actuated actuation behavior of the user; wherein the control device (9) is further programmed - to determine both a preferably first feedback time (tF _{n_1} ) and a preferably first actuation time (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) or the last feedback time (tF _{n_4} ) respectively assigned Concentration (C(t)) in the body, especially in the blood; - for determining a concentration curve over time from a group of concentration curves over time associated with the same dose, in particular models or PK curves (PK50 _+SD , PK50 _M and PK50 _-SD ), from a large number of time curves stored in the data memory (M) and associated with the same dose Concentration courses, in particular PK models or PK curves, taking into account both the preferably first feedback time (tF _{n_1} ) and one of the preferably first actuation times (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , …) or the last feedback time (tF _{n_4} ) ordered concentration; and - to take into account the individual concentration profile determined over time, in particular the individual PK curve (PK _Ind ) determined, when predetermining the level of one or more of the subsequent application doses (D ₃ , D _n , D _n+1 , ...). 29. Nasal applicator (100) according to claim 27 or 28, wherein the control device (9) is further programmed, - when predetermining the level of the next application dose (D _n ), the set target concentration (C _ED ) or its maximum value and/or the time determined individual concentration profile, in particular the determined individual PK curve (PK _Ind ), must be taken into account.

30. nasal applicator (100) according to any one of claims 9 to 29, wherein the control device (9) is further programmed - to determine, after delivery has taken place, an initial dose (D ₀ ) which was delivered at a delivery time (tA ₀ ). or for a first actuation time (tB ₁ ), which is after the delivery time (tA ₀ ) of the initial dose (D ₀ ), for a group of concentration courses over time assigned to the same dose, in particular models or PK curves (PK50 _+SD , PK50 _M and PK50 _-SD ), from a large number of concentration courses over time stored in the data memory (M) and assigned to the same dose, in particular PK models or PK curves, each have a concentration (C _{ED1_+SD} , C _{ED1_M} ) assigned to the first actuation time (tB ₁ ). , C _{ED1_-SD} ), and for setting the concentrations determined in this way (C _{ED1_+SD} , C _{ED1_M} , C _{ED1_-SD} ) in each case as an estimated target concentration of the associated concentration curve over time; - for applying the initial dose (D ₀ ) following the first application dose (D ₁ ) in response to the actuation of the retrieval device (1) at the first actuation time (tB ₁ ); - to determine the temporal concentration curves of the group, to which Time after the application of the first application dose (D ₁ ) the concentration in the body, in particular in the blood, will have fallen again to the estimated target concentration of the associated concentration curve over time, and for setting the time determined for the concentration curves of the group over time as calculated target concentration time point (tB _{2_+SD} , tB _{2_M} , tB _{2_-SD} ); - For detecting or determining the second actuation point in time (tB ₂ ) for retrieving a second or subsequent application dose (D ₂ ); - to determine a concentration curve over time from the group as an individual concentration curve over time, in particular as an individual PK curve (PK _Ind ), taking into account the respective difference between the calculated target concentration time (tB _{2_+SD} , tB _{2_M} , tB _{2_-SD} ) of each concentration curve over time from the group and the second activation time (tB ₂ ), in particular the concentration curve over time which has the smallest difference between its calculated target concentration time (tB _{2_+SD} , tB _{2_M} , tB _{2_-SD} ) and the second activation time (tB ₂ ). ; and - to take into account the determined individual concentration profile over time, in particular the determined individual PK curve (PK _Ind ), when Predetermining the level of one or more of the following application doses (D ₃ , D _n , D _n+1 , ...). 31. Nose applicator (100) according to one of claims 9 to 30, wherein the control device (9) is further programmed - to determine the at least one considered actuation time (tB _n-1 ) or at least one considered pre-determination time (tV _n-1 ) concentration of the substance (S) present in the user's body or blood, and setting this concentration as the target concentration (C _ED ); and wherein the control device (9) is further programmed in order - at the next predetermination time (tV _n ) to set the level of the next application dose (D _n ) in such a way that the concentration in the body or in the blood of the user only begins after a predetermined period of time has elapsed from the delivery time (tA _n ) of the next application dose (D _n ), will fall again to the target concentration (C _ED ). 32. Nose applicator (100) according to any one of the preceding claims, wherein - the evaluation of the means of the detection device (11) detected actuation behavior of the user the detection of actuations of the retrieval device (1) by the user at actuation times (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within one of the blocking periods (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , …) includes; - The control device (9) is further programmed to determine one of the actuation times (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within one of the blocking periods (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _{n +1} , ...) associated concentration (C(t)) in the body, especially in the blood; - Set the target concentration (C _ED ) or its minimum value to a value above the assigned concentration (C(t)). 33. Nose applicator (100) according to claim 32, - wherein the detection device (11) is further programmed to detect at least one actuation of the retrieval device (1) by the user at actuation times (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...); wherein the control device (9) is further programmed - to determine an actuation time (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , ... , T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) respectively assigned Concentration (C(t)) in the body, especially in the blood; - To determine a concentration profile of the group over time, taking into account at least one, preferably the last, actuation time (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) and at least one, preferably the first, actuation time (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , …, T_vain _n-1 , T_vain _n , T_vain _n+1 , …); and - to take into account the determined individual concentration profile over time, in particular the determined individual PK curve (PK _Ind ), when predetermining the level of one or more of the subsequent application doses (D ₃ , D _n , D _n+1 , ...). 34. Nose applicator (100) according to one of the preceding claims, wherein - the evaluation of the user's actuation behavior detected by means of the detection device (11) includes the evaluation of actuations of the retrieval device (1) by the user at actuation times (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within one of the blocking periods (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...); - The control device (9) is further programmed to determine an increase in the time intervals between successive actuation times (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within one of the blocking periods (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) or the absence of further actuation times (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _{n+ 1} , ...), and for determining a point in time from which the degree of increase or lack of it satisfies predetermined criteria; - the control device (9) is further programmed to determine a time-associated concentration (C(t)) in the body, in particular in the blood; - Set the target concentration (C _ED ) or its minimum value to a value above the assigned concentration (C(t)). 35. Nose applicator (100) according to claim 34, wherein the control device (9) is further programmed - to evaluate at least one detected actuation of the retrieval device (1) by the user at actuation times (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...); wherein the control device (9) is further programmed - -to determine an actuation time (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) associated concentration (C(t)) in the body, especially in the blood; - to determine a concentration profile of the group over time, taking into account both one, preferably the last, actuation time (tB _{1_v1} , tB _{2_v1} , tB _{1_v2} , tB _{2_v2} ) within the blocking period (T_vain ₁ , T_vain ₂ , ..., T_vain _n-1 , T_vain _n , T_vain _n+1 , ...) and one, preferably the first, actuation time (tB ₁ , tB ₂ , ..., tB _n-1 , tB _n , tB _n+1 , ...) after the blocking period (T_vain ₁ , T_vain ₂ , …, T_vain _n-1 , T_vain _n , T_vain _n+1 , …); and - to take into account the determined individual concentration profile over time, in particular the determined individual PK curve (PK _Ind ), when predetermining the level of one or more of the subsequent application doses (D ₃ , D _n , D _n+1 , ...). 36. System comprising - one or more nasal applicators (100) according to one of the preceding claims; - one or more peripheral devices (101); wherein the one or more nasal applicators (100) are in signal or communication connection with one or more of the peripheral devices (101) or are prepared or programmed for this purpose.