DE102008026696A1 - Active ingredient depot for releasing active substance, comprises substrate with opening, and multiple individual reservoirs for active substance - Google Patents

Abstract

An active ingredient depot (100) comprises a substrate (110) with an opening, and multiple individual reservoirs (120) for active substance, where the individual reservoirs are designed in opening of the substrate. A fluid duct (130) is interconnected with the multiple reservoirs. A membrane (140) for separating fluid duct of the individual reservoirs is also included and has a signal connector. The substrate is designed as a folded foil. Independent claims are included for: (1) a dosing system for controlled delivery of a drug, which comprises a reservoir for a carrier, a pressure chamber, and a device for receiving active ingredient depot; (2) a method for controlled releasing of active substance by using dosing system, which involves creating pressure in the reservoir by a pressure medium; and (3) a method for manufacturing active ingredient depot, which involves forming opening in the substrate, where multiple individual reservoirs are designed in the opening.

Description

The The present invention relates to a drug depot and a Dosing system for a controlled release of an active substance and in particular a dosing system with discrete, controlled substance addition.

In Medicine is common that agents over longer periods and infusion pumps are often used Commitment. Infusion pumps allow a physiological and medical optimized and therefore safe parenteral administration of drugs. there it can be very different agents, such as Tranquillizers, chemotherapeutic agents, analgesics, active ingredients in intensive care, artificial nutrition etc. To the mobility to get the patient for certain medical conditions or If necessary, portable infusion pumps can also be used be used. These portable infusion pumps are for example on the belt, attached under clothing or directly on the skin. such Systems have become, for example, in the treatment of diabetes for transdermal Administration of insulin.

to as far as possible maintaining as constant a bioavailability as possible however, it is common for the active ingredient required that at intervals of several days the access (port) of Patient or by the attending physician. Thereby is a local drug accumulation, constipation of the catheter or a denaturation of the local tissue counteracted. There the appropriate drug in this case into the adipose tissue administered, there is a reduced risk of infection.

in the Case of intravenous or spinal drug administration, however, are sterile conditions of the highest Importance. In chemotherapy, spasticity therapy or pain therapy That is why implantable infusion pumps have become established. These systems can be roughly divided into constant flow systems as well as systems with controllable flow rate. For constant flow systems after implantation, an unchangeable delivery rate occurs during which time For controllable systems, the delivery rate also in the implanted state can be varied.

established, implantable constant flow systems are based on a uniform Principle: a drug reservoir with variable volume is in one second, non-variable volume arranged. The gap is with a refrigerant filled, which at the intended use temperature of the system (for example the body temperature) evaporates and thereby build up a pressure. By dimensioning the degree of filling with refrigerant can be thus adjust that independently from the inner, variable volume, the refrigerant always as a two-phase mixture is present. This makes it independent from the current filling level of the drug reservoir the vapor pressure of the refrigerant on the drug. In the known constant flow systems, the release rate (flow rate, d. H. delivered amount of active ingredient per unit time) over a flow resistance set. Once the systems are implanted, the dispensed drug amount only about their concentration in the drug solution be varied. This, however, will increase the flexibility of each Therapy severely limited.

at implantable infusion pumps with controllable flow rate is the Drug flow in dependence of the need ("on demand ") controlled by a peristaltic pump. The peristaltic pump can be driven for example by an AC motor. Although systems with controllable flow rate are more expensive and more expensive than constant flow systems, Nevertheless, their use is possibly the cheaper alternative because - as described above - in constant flow systems the release rate of drug only by its concentration in the administered solution can be adjusted. However, this requires, for example, one complete Emptying the reservoir and a subsequent refilling. The resulting costs in the clinical trial phase (z. B. finding an optimal drug concentration for a therapy to be performed) can drastically reduced by the use of controllable systems. The duration of use of such controllable systems is determined by the energy consumption determined and is for example up to eight years. By a reduced energy consumption of newer systems could be the Duration of use can be further increased. Of far greater interest is however a possible one Reduction of the size (for example increase acceptance) or an extension of the refill intervals for the Drug solution typically associated with a hospital stay, too to reach.

For example, the constant flow systems have a diameter between 50 and 100 millimeters or between 76 and 86.4 millimeters, a height between 15 and 40 millimeters or between 20 and 37.4 millimeters, and weigh, for example, in a range between 80 and 200 grams or between 100 and 173 grams. Possible reservoir volumes are in a range between 10 and 100 milliliters or, for example, 16, 20, 30, 35, 40, 50, 60 milliliters. For example, the flow rates over a period of 24 hours range between 0.1 and 10.0 milliliters / 24 hours or between 0.5 to 4.0 or between 0.3 to 4.0 or between 0.37 to 3.6 milliliters / 24h.

The dimensions of controllable flow rate systems are, for example, in a range between 80 and 100 millimeters or at about 85 millimeters or 87 millimeters and the height is for example in a range between 15 and 40 millimeters or at about 19.5 or 27.5 millimeters. The weight of systems with controllable flow rate is, for example, in a range between 150 and 200 grams or about 165 grams or about 185 grams. The Volume of the reservoir of systems with controllable flow rate is for example between 10 and 100 milliliters or at about 10, 20, 18 or 40 milliliters. The flow rates of controllable systems are for example in a range between 0.01 and 50.0 or in one Range between 0.048 and 21.6 milliliters per 24 hours or in a range between 0.048 and 24 milliliters per 24 hours.

A Another variant of conventional drug dosage systems allows a sequential opening of individual reservoirs. The drug to be administered is located doing so in equal doses in individual sealed reservoirs (Individual reservoirs), which are opened electronically controlled as needed can. This can be achieved, for example, by an electrochemical dissolution of a Gold membrane or melting a titanium or platinum membrane by a short current pulse resulting from a voltage of approx. 4 volts, happened. These systems can, for example, directly can be implanted under the main and, for example, for a controlled Dosage of hormones to be applied in osteoporosis therapy.

adversely in such systems, however, is the limited, uncontrollable and not previously determinable bioavailability of the administered Single doses. This is because, for example, that uncontrollable Tissue irritation, proliferation of the system by scar tissue or a resulting encapsulation the further transport of the drug or drug. Thus, the active ingredient for the body not available.

outgoing from this prior art, the present invention is the Task based, an agent depot, a drug dosing and to provide a manufacturing process that is a discrete, controlled one Drug delivery allows and at the same time their bioavailability ensures.

These The object is achieved by an agent depot according to claim 1, a dosing system according to claim 10, a dosing method 18 and a manufacturing method solved according to claim 20.

Of the The present invention is based on the finding that an active ingredient or a substance in a multiplicity of individual reservoirs, which in a substrate can be stored, can be stored, wherein a fluid channel the Einzelreservoire connects and between the fluid channel and the Single reservoirs a membrane is arranged. The membrane is designed such that they are on a signal for the active substance is passable and thus a controlled release of Active substance or the substance can be made in the fluid channel.

at further embodiments the fluid channel is part of a system of channels, the channels with a reservoir for a carrier liquid connected so that the carrier liquid after an activation through the channels flows and finally about one Substance exit (delivery point for the active ingredient) the body supplied becomes. The activation can, for example, with the training of a Vapor pressure when reaching a certain temperature (eg below the body temperature) happen. The current flow of the carrier liquid can the individual reservoirs through the system of channels in one serial or parallel power supply to reach. The carrier liquid more generally, can also be a vehicle (eg a gaseous Medium).

Further embodiments also describe a metering system for controlled delivery an active substance to an environment, wherein the dosing a Active ingredient outlet or a fluid outlet or a substance outlet, further a reservoir for a vehicle and an agent depot (or substance depot). The reservoir is connected to the substance outlet and trained after Activation a flow of the vehicle to create. Agent depot has a variety of individual reservoirs for the active ingredient on. The activation can in turn be done as described above, the reservoir having, for example, a stretchable part (bellows) can, the the forming steam pressure on the vehicle in the reservoir transfers, so that the carrier power is formed. The drug depot is formed, for example, to the active ingredient in the individual reservoirs sequentially (eg Signal) to the carrier substance leave.

at the active ingredients are not just medical or pharmaceutical Products act, but generally include substances that have an effect cause the effect in addition to biological or chemical also of an aesthetic nature can be (eg smell, appearance, color etc.).

embodiments thus provide a combination of a drug constant flow system and a drug dosing system operating on the sequential opening of Single reservoirs is based, wherein a fluid channel as a connecting channel is formed between the individual reservoirs.

embodiments for the Promote drug dosage system continuously and constantly a carrier stream, for example a physiological saline solution can have. The constant carrier current can be generated for example by means of a vapor pressure drive, so that extra electrical energy is not required. This carrier stream flows around or flows through the drug depot, which is in a variety of individual reservoirs is divided. In a conceivable, volume-saving embodiment this drug depot as a structured, multi-layered film with internal channel structures (a fluid channel formed to the system of channels) for flushing executed. The channel structure can either meander over a surface of the Substrate extend as well several layers of the substrate are guided. Thus, can itself the channel structure formed both horizontally and vertically meandering be.

Around For example, administer a drug to a patient single or multiple individual reservoirs open and the active substance contained therein is brought into direct contact with the carrier stream and with this administered to the patient.

One clear advantage of the systems according to the invention over the For example, in conventional systems, the Active ingredient though highly can be stored concentrated, but the patient always in administered at a lower concentration. By the continuous carrier power becomes a back diffusion of drug solution or body fluid prevented in the system as well as a good distribution of the active ingredient ensured in the area / environment of the application site.

at conventional systems which dose a premixed drug solution, is the proportion of active ingredient in the administered drug solution usually only between 2 and 3%. Depending on the medication, this requires that corresponding reservoir at intervals of about 3 to 8 weeks in a clinic refilled by means of an injection in a refill port or replenished becomes. This process requires specially trained medical Staff, as a misinterpretation for the patient, for example can be life threatening. However, the active ingredient is as in embodiments the present invention already for the duration of use of the pump sufficiently stored in the system, is only predefined Intervals carrier fluid refill. A such injection of carrier fluid could be from a trained patient himself. A misinterpretation beyond that In this case, only the result that the pump can not continue to promote - however would no life-threatening situations arise. In addition will by the dry storage of the active substance in the system of its permissible storage time or durability significantly increased. great economic potential for systems according to the invention especially in areas where regular doctor visits are not expected realistic feasible are.

at further embodiments the individual reservoirs are filled with different active ingredients, so that different individual reservoirs in the drug depot different Active ingredients contain and thereby different with one and the same pump Active ingredients independently can be dosed from each other. This provides a further advantage with respect to conventional systems which are designed for one active substance only.

preferred embodiments The present invention will be described below with reference to FIG the enclosed drawings closer explained. Show it:

1 a cross-sectional view through a drug depot according to an embodiment of the present invention;

2 a plan view of a channel portion of the fluid channel in the drug depot;

3 schematic representation of conventional implantable constant flow systems;

4 schematic representation of a conventional system with controllable flow rate;

5 an implantable conventional drug dosage system;

6A and 6b a design of the individual reservoirs of the implantable conventional drug dosage system;

7A - 7C Opening individual reservoirs of the implantable conventional drug delivery system;

8th schematic representation of a possible embodiment of a drug dosing system;

9A B a single reservoir with closed and opened membrane; and

10A to 10C a single reservoir with saline crystals (not yet closed, closed, opened).

Before In the following the present invention will be explained in more detail with reference to the drawings pointed out that the same elements in the figures with the same or similar Reference numerals are provided, and that a repeated description is left out of these elements.

1 shows a cross-sectional view of a drug depot 100 with a substrate 110 with recesses, in the individual reservoirs 120 are formed. The individual reservoirs 120 are by means of a fluid channel 130 connected together, being along the fluid channel 130 a carrier stream 132 can flow, for example, in succession all individual reservoirs 120 happens. The individual reservoirs 120 are from the fluid channel 130 through a membrane 140 separated, with the membrane 140 is selectively opened to a signal, so that in the individual reservoirs 120 deposited drug to the carrier stream 132 is delivered. The drug depot 100 may for example have a multi-layered shape, so that the Einzelreservoire 120 in a first shift 120a in a second layer 120b , ... until, for example, in a sixth shift 120e are arranged one above the other. Individual neighboring drug depots 120a , b are, for example, with a backside membrane 142 separated from each other.

The substrate 110 For example, it can be layered so that the fluid channel 130 flows through different layer planes, with an (optional) via 134 the fluid channel 130 from one layer level to the next. The fluid channel 130 can thus meander on a surface of the substrate 110 extend or also be formed meandering in the vertical direction. The points above and below are intended to indicate that this form can continue accordingly. The shape of the individual reservoirs 120 is in the in cross-sectional view 1 assumed to be trapezoidal, in other embodiments the individual reservoirs 120 may have a different shape (for example, cuboid).

2 shows a plan view of the fluid channel 130 , The fluid channel 130 for example, on the substrate 110 or in the substrate 110 be formed, in the latter case, the 2 a cross-sectional view through the substrate 110 along the fluid channel 130 represents (eg along the section line AA 'in 1 ). The fluid channel 130 is from the individual reservoirs 120 through the membrane 140 is separated, with the individual reservoirs 120 in the in 2 embodiment shown below the membrane 140 are arranged. Furthermore, the shows 2 that contact or signal connections 150 on or in the membranes 140 are formed, for example, serve the Einzelreservoire 120 selectively open. These can be the signal connections 150 for example heating element 153 have, so that the opening of the membranes 140 for example, by applying a signal to the signal terminals 150 , which causes melting of the membrane takes place. Alternatively, the presence of a signal can also cause the membrane 140 permeable to the active ingredient.

If no signal at the signal terminals 150 rests, separates the membrane 140 the underlying individual reservoir 120 from the fluid channel 130 , so no mixing between that in the individual reservoir 120 placed drug with the carrier stream 132 that extends along the fluid channel 130 moves, takes place. The signal connections 150 For example, they can be connected to a control and regulating device, which then individual membranes 140 open so that in the individual reservoirs 120 placed drug in the fluid channel 130 can escape. The control and regulating device can, for example, several membranes 140 open simultaneously or sequentially individual membranes 140 open or at a given time intervals membranes 140 to open.

The fluid channel 130 For example, a cross section perpendicular to the direction of flow 132 (which is, for example, round, rectangular, square) and amount to an area which is at least as large as a membrane area of the membrane 140 , Alternatively, the cross-sectional area of the fluid channel 130 also be smaller than 10 times the membrane area.

The 3A to 3c give a schematic representation of three conventional implantable constant flow systems.

In 3A is a first constant flow system shown with a filling cannula 310 , a filling septum 320 , a filling reservoir 330 , into the over the filling cannula 310 an active ingredient can be introduced. There is also a fixing plate 333 formed as a stopper obstacle for the filling cannula 310 serves (so that when filling a fixed end point for the cannula 310 is provided) and an optional eyelet 420 Can be used to fix the Konstantflusssys system. The filling reservoir 330 is with a drug reservoir 340 connected. Furthermore, the first constant flow system has a filter 350 on, through which the active ingredient from the drug reservoir 340 in an outlet reservoir 360 is transportable and the outlet reservoir 360 with a substance output 370 (or a substance delivery point) is connected. Finally, the Konstantflusssys in the 3a a stretchable vessel part 380 (which may be designed, for example, in the form of a bellows or expansion vessel), which serves to ensure the most constant possible pressure (eg gas pressure) in the active substance reservoir 340 to produce so that the active ingredient through the filter 350 to the substance exit 370 is directed. The drug depot 340 For example, in a pressure chamber 430 be arranged.

3B shows a second conventional constant flow system adjacent to the filling cannula 310 also a cannula for connecting a catheter 410 having. The drug depot 340 again has a stretchable part 380 on, so that in the drug depot 340 a constant pressure can develop. The elastic part 380 may for example comprise titanium. The active ingredient in the drug depot 340 will turn through the filter 350 forwarded to the substance exit or to the catheter.

3C shows a third example of a conventional constant flow system, which in turn the filling cannula 310 that passes through the stop plate 333 can be fixed. Furthermore, the constant flow system again has a septum 320 and a filter 350 on, with the septum 320 serves to make a seal when inserting the cannula and the filter 350 a filtering of the drug is used before it is supplied to the substance output. The drug depot 340 again has a stretchable section 380 on, so in the drug depot 340 a constant pressure can be formed.

4 gives a schematic representation of a system with controllable flow rate, the controllable flow rate system comprising, for example, the following components: a substance output 370 , an injection membrane 440 which is secured by a steel sleeve, for example, a peristaltic pump 380 , a filling septum 320 , a battery 490 , a fixation plate 333 for the filling cannula 310 , the active ingredient reserve 340 , a filter 350 (For example, a so-called Bioretentionsfilter). Further, for example, a noble gas in a space 492 between the drug depot 340 and the outer pressure vessel 430 be introduced. In addition, the controllable flow rate system has electrical modules 455 on and a side entrance 440 , The substance output 370 For example, it may optionally have a catheter.

5 shows a conventional system for drug dosage by sequential opening of individual reservoirs and the 6A and 6B show a possible design of the individual reservoirs used in detail.

In 6A are the individual reservoirs 120 in the substrate 110 arranged, with the individual reservoirs 120 on a surface 112 of the substrate 110 through a membrane 140 are closed. The substrate surface 112 is formed for example by a silicon dioxide or silicon nitride layer. Further, for example, on the surface 112 a cathode 154 and anodes 152 formed so that upon application of a corresponding electrical signal, the membrane 140 that the individual reservoirs 120 on the surface 112 closes, is opened (for example by electrochemical dissolution of the membrane 140 ). The substrate 110 For example, silicon may be silicon and the surface may be formed by oxidation or by forming a silicon nitride layer.

6B shows a room view of a single reservoir 120 , which is designed in the form of a dull pyramid with a rectangular base. The base is through the backside membrane 142 closed and the side surfaces are through the substrate 110 educated. The pyramid-shaped individual reservoirs 120 have no tip and the membrane 140 instead forms an upper edge of the individual reservoir 120 , The membrane 140 and the backside membrane 142 thus form an upper and lower end of the pyramid-shaped individual reservoirs 120 - which in turn through recesses in the substrate 110 are formed. In the individual reservoirs 120 For example, before sealing with the membrane 140 or the backside membrane 142 the active ingredient or the drug is introduced.

The electrical contacting of the anode 152 and the cathode 154 in turn, by means of the control terminals 150 happen.

The 7A and 7B show a plan view of the along the substrate surface 112 through the membrane 140 closed individual reservoirs 120 , where in the 7A the single reservoir through the membrane 140 is closed and in the 7B the individual reservoir 120 after dissolution of the membrane 140 is shown. The membrane 140 is doing over the signal contacts 150 electrically contacted. In the 7A is the membrane 140 shown throughout, while in the 7B the membrane 140 just outside the hatched region, which is the open single reservoir 120 represents, is formed.

7C shows a room view of the through the membrane 140 closed single reservoir 120 , These are also on the substrate surface 112 trained railways 150 and the back closure 142 (can for example also be done by a soldering seal).

8th shows an embodiment of the present invention for a discretely controlled dosing system, for example, a pressure chamber 430 and has an eyelet 420 can be fixed. Inside the pressure chamber 430 is a reservoir 340 for the carrier substance (for example a saline solution), which has an extensible component 380 has, so that the volume of the reservoir 340 is variable. The reservoir 340 for the vehicle is with a Einfülldepot 330 connected, leaving a filling cannula 310 the vehicle through a septum 320 can fill. For fixing the filling cannula 310 is a fixing plate 333 formed, for example, a solid resistance during filling or during insertion of the substance cannula 310 offers.

According to the invention is between the reservoir 340 for the vehicle and the filter 350 an agent depot 100 arranged so that the carrier substance from the reservoir 340 over the fluid channel 130 the drug depot 100 happens and then after passing the filter 350 to a substance exit 370 is forwarded. The fluid channel 130 happens here a variety of individual reservoirs 120 , where the individual reservoirs 120 contain the active ingredient, which is then controllable to the carrier stream 132 can be delivered. Is exemplary in the 8th shown as the single reservoir 120b is open and the active ingredient from the individual reservoir 120b in the fluid channel 130 is delivered. The opening of the individual reservoirs 120 takes place, for example sequentially and can by means of the signal terminals 150 to be controlled.

The fluid channel 130 happens successively the multiplicity of individual reservoirs 120 , so that sequentially all drug depots 120 can be opened. This can be done individually or optionally also several individual reservoirs 120 be opened at the same time. It is also possible that different individual reservoirs 120 contain different active ingredients, so that, depending on the needs, various active ingredients in the carrier stream 132 can be delivered. The carrier current 132 is formed by the carrier, for example, in the reservoir 340 is stored and, for example, has a saline solution. At regular intervals, by means of the filling cannula 310 the reservoir 340 be filled.

The drug depot 100 can be realized for example as follows. In a structured layer, which may comprise, for example, silicon, glass, metal or plastic, individual cavities are formed, which are unilaterally through membranes 140 be closed. These membranes 140 in turn, for example, carry heater structures 150 via the signal connections 150 be contacted. It can also be other structures, which a later controlled opening of individual membranes 140 enable, be trained. After filling the individual reservoirs 120 with one or more active ingredients, a second layer may be applied to seal the individual reservoirs (the backside membrane) 142 ), wherein this sealing layer can be formed, for example, by a lamination, gluing or welding. The resulting layer stack can now be rolled or stacked into a dosing system for proper placement or docking, depending on the materials selected (see 8th ). The intermediate channel structures of the fluid channel 130 and fluidic vias 134 allow a uniform and exactly predetermined flow of a so-designed drug depot 100 ,

The 9A and 9B show an experiment with individual reservoirs, which are formed for example in silicon, wherein membranes are made of silicon nitride, filled with substances on the back and are subsequently closed by means of an adhesive strip. These structures were adhered to a carrier board, which contacted wires with heating structures, and this assembly was placed in a water-filled beaker.

9A shows a single reservoir 120 passing through a membrane 140 is closed, with a heater structure 153 on the membrane 140 is formed and through the signal terminals 150 will be contacted. The membrane 140 For example, it may include silicon nitride and the heater structure 153 be formed of a metal. In the in 9A As shown, the single reservoir is filled with an ink solution. Through a short-term current through the heater structure 153 (For example, by applying 10 volts), the membrane 140 destroyed and the spontaneous exit 510 the ink solution becomes noticeable (see 9B ), where the line 141 the opened membrane 140 to indicate. One in the individual reservoir 120 active ingredient could then be transported away from a carrier stream.

An analogous experiment is in the 10A to 10C shown, with the single reservoir 120 now filled with saline crystals. 10A shows the saline crystals in a still closed sensor cavity (single reservoir 120 ). The 10B and 10C On the other hand, show how in an exemplary beaker experiment, the principle of operation of the substance delivery proposed by the invention can take place. While the sensor membrane 140 in the 10b is still intact, is the sensor membrane 140 in the 10C open. The salt crystals can now be in solution with the medium in the beaker 520 walk. Opening the sensor membrane 140 in turn, by means of a heater structure 153 done when creating an ent speaking signal at the signal terminals 150 the membrane 140 destroyed or opened. The membrane 140 For example, it may again comprise silicon nitride and the heater structure 153 have a metal. The filling with saline crystals is chosen as an illustrative example to prevent leakage in the individual reservoir 120 substance or active ingredient in an environment to illustrate.

Thus, embodiments include a metering system that provides a continuous carrier stream 132 permit, wherein the carrier stream intermittently and controllably agents or substances are buried. In particular, this dosing system may comprise a portable drug dosing system.

Further include embodiments as well Metering systems, for example, for ventilation systems or air conditioning systems used to create a carrier airflow for example, with fragrances or other ingredients. at the active ingredients are not just medical or pharmaceutical Products can act, but can include general substances that cause an effect wherein the effect can be especially of an aesthetic nature (eg smell, appearance, color etc.).

Embodiments thus offer the possibility of modifying established constant flow systems in terms of safety and controllability, which modification may include the use of alternative materials for the membrane structure or of multilayer channel structures with internal metallizations. Furthermore, the media permeability of various conceivable materials for the membrane 140 be designed so that the included drug has sufficient long-term stability. The membrane 140 For example, it should not be permeable to substances that could adversely affect the activity of the substance. Furthermore, the temperature regime in the individual cavities with a thermal opening of the same should be taken into account, whereby possibly also alternative methods for cavity (membrane) opening are taken into consideration.

In a further embodiment, the plurality of Einzelreservoire 120 be replaced by one or more membranes with controllable permeability.

at further embodiments is the drug to be administered in equal doses in individual sealed reservoirs (individual reservoirs), the can be opened electronically controlled as needed. This For example, by an electrochemical dissolution of a gold membrane or melting a titanium or platinum membrane by a short Current pulse, resulting from a voltage of about 4 volts, done.

Embodiments are thus particularly advantageous in that when using the steam pressure drive no electrical energy to generate the pressure in the reservoir is required. As already described above, the vapor pressure is generated when an activation temperature is exceeded in that a pressure medium, for example, passes into the gaseous phase and the resulting 2-phase mixture generates a vapor pressure. The vapor pressure thus generated is very constant over a long period of time and is essentially dependent only on the temperature. As the body temperature barely changes, the constant pressure gradient also creates a constant carrier flow. Since no energy is consumed to generate pressure, moreover, only very little heat is generated. In addition, the meandering configuration (eg, horizontal as well as vertical) of the drug depot creates 100 a huge amount of space. In contrast to conventional solutions, embodiments are thus very well suited for implantation.

embodiments For example, the present invention provides economic benefits with regard to a simplified medical approval and a conceivable development new markets. For example, the simple medical approval can be expected, since alternative designs of existing approved Systems can be used and not a complete new development is required. For example, the new markets can markets cover up to now for implantable drug delivery systems were not accessible. Here are in particular also sparsely populated To call areas (such as Australia), where regular clinic visits for refilling of the system with drug solution through medically trained professionals are not realistic.

Claims (21)

Drug depot ( 100 ) for receiving an active substance, comprising: a substrate ( 110 ) with recesses; a large number of individual reservoirs ( 120 ) for the active substance, whereby the individual reservoirs ( 120 ) in the recesses of the substrate ( 110 ) are formed; a fluid channel ( 130 ), which covers the multiplicity of individual reservoirs ( 120 ) connects together; and a membrane ( 140 ), which the fluid channel ( 130 ) from the individual reservoirs ( 120 ) and a signal connection ( 150 ) having, the membrane ( 140 ) to a signal on the signal port ( 150 ) into one for the active ingredient from at least one individual reservoir ( 120 ) from the multiplicity of individual reservoirs ( 120 ) passable state is brought. Drug depot ( 100 ) according to claim 1, wherein the fluid channel ( 130 ) meandering through the substrate ( 110 ) or along a substrate surface. Drug depot ( 100 ) according to one of the preceding claims, in which the substrate ( 110 ) is formed as a folded film. Drug depot ( 100 ) according to one of the preceding claims, in which the membrane ( 140 ) is formed so that the signal at the signal terminal ( 150 ) a melting of the membrane ( 140 ) causes. Drug depot ( 100 ) according to one of claims 1 to 3, in which the membrane ( 140 ) has a controllable permeability for the active substance, so that the signal at the signal terminal ( 150 ) controls the permeability. Drug depot ( 100 ) according to one of the preceding claims, in which the plurality of individual reservoirs ( 120 ) layered in the substrate ( 110 ) are arranged. Drug depot ( 100 ) according to one of the preceding claims, which has a further fluid channel and the further fluid channel is formed, so that a carrier flow onto the fluid channel ( 130 ) and the further fluid channel is divisible and the carrier flow ( 132 ) in the parallel flow direction different individual reservoirs of the plurality of individual reservoirs happens. Drug depot ( 100 ) according to one of the preceding claims, in which the membrane ( 140 ) a membrane surface and the fluid channel ( 130 ) one in the current direction ( 132 ) has a vertical cross section, wherein a surface of the cross section is at least as large as the membrane surface and smaller than ten times the membrane surface. Dosing system for the controlled delivery of an active substance to an environment, comprising: a substance outlet ( 370 ); a reservoir ( 340 ) for a carrier substance, wherein the reservoir ( 340 ) with the substance output ( 370 ) and has a variable volume such that a carrier stream ( 132 ) of the carrier substance to the substance output ( 370 ) can be generated by a pressure gradient; a pressure chamber ( 430 ) for receiving a pressure medium and the reservoir ( 340 ), wherein the pressure medium is formed to a gas pressure in the pressure chamber when an activation temperature ( 430 ) and thereby to produce the pressure gradient; and a device for receiving a drug depot ( 100 ) according to one of claims 1 to 8, such that the fluid channel ( 130 ) on the one hand with the substance output ( 370 ) and on the other hand with the reservoir ( 340 ) connected is. Dosing system for the controlled delivery of an active substance to an environment, comprising: a substance outlet ( 370 ); a reservoir ( 340 ) for a carrier substance, wherein the reservoir ( 340 ) with the substance output ( 370 ) by means of a fluid channel ( 130 ) and the reservoir ( 340 ) has a variable volume such that a carrier stream ( 132 ) of the carrier along the fluid channel ( 130 ) to the substance exit ( 370 ) can be generated by a pressure gradient; a pressure chamber ( 430 ) containing a pressure medium and the reservoir ( 340 ), wherein the pressure medium is formed to a gas pressure in the pressure chamber when an activation temperature is exceeded ( 430 ) and thereby to produce the pressure gradient; and an agent depot ( 100 ), which has a large number of individual reservoirs ( 120 ) for the active substance and the fluid channel ( 130 ) the drug depot ( 100 ), whereby the drug depot ( 100 ) to sequentially form the drug in the individual reservoirs ( 120 ) to the carrier substance. Dosing system according to claim 10, wherein the fluid channel ( 130 ) is designed to manage the individual reservoirs ( 120 ) and the individual reservoirs ( 120 ) from the fluid channel ( 130 ) through a membrane ( 140 ) are separated. Dosing system according to claim 11, in which the membranes ( 140 ) a heating structure ( 153 ), wherein the heating structure ( 153 ) is formed in order, when applying a heating signal, the membrane ( 140 ) thermally open, so that an active substance from the individual reservoirs ( 120 ) in the carrier stream ( 132 ). A dosing system according to claim 11 or claim 12, wherein the drug depot ( 100 ) is designed to be stored in the individual reservoirs ( 120 ) to take up various active substances and in which the membranes ( 140 ) are designed to contain the individual reservoirs filled with different active substances ( 120 ) individually. Dosing system according to one of claims 10 to 13, in which the individual reservoirs ( 120 ) in a substrate ( 110 ) are arranged in layers, wherein two adjacent layers by a seal layer ( 142 ) are separated from each other. Dosing system according to Claim 14, in which the sealing layer ( 142 ) has a laminate layer or an adhesive layer. Dosing system according to one of claims 11 or 13 to 15, in which the membrane ( 140 ) has a controllable permeability to the active substance and the controllable permeability by applying a signal to a signal terminal ( 150 ) is controllable. Dosing system according to one of claims 10 to 16, wherein the active ingredient is a pharmaceutical product or a Includes fragrance. Method for the controlled delivery of an active substance to an environment by means of a dosing system which has a substance output ( 370 ), a reservoir ( 340 ) and an agent depot ( 100 ) connected to a fluid channel ( 130 ), wherein the drug depot ( 100 ) a plurality of individual reservoirs ( 120 ) for the active substance, comprising the following steps: forming a pressure in the reservoir ( 340 ) by a pressure medium, so that when an activation temperature is exceeded, a gas pressure is generated and a carrier flow from the reservoir ( 340 ) to the substance exit ( 370 ) is formed; and opening individual reservoirs ( 120 ), so that the active substance from the individual reservoirs ( 120 ) is delivered to the carrier stream. The method of claim 18, wherein the step of opening comprises applying a signal to a signal port ( 150 ), so that a membrane ( 140 ), which the fluid channel ( 130 ) from the individual reservoirs ( 120 ), for the active ingredient from at least one individual reservoir ( 120 ) from the multiplicity of individual reservoirs ( 120 ) becomes passable. Process for the production of a drug depot ( 100 ), comprising: forming recesses in a substrate ( 110 ); Forming a variety of reservoirs ( 120 ) in the recesses of the substrate ( 110 ); Filling the multitude of individual reservoirs ( 120 ) with one or more active substances; Forming a fluid channel ( 130 ), which covers the multiplicity of individual reservoirs ( 120 ) connects together; and forming a membrane ( 140 ), which separate the fluid channel from the individual reservoirs ( 120 ) separates; and forming a signal terminal ( 150 ), whereby the signal connection ( 150 ) is formed, that the membrane ( 140 ) to a signal on the signal port ( 150 ) for the active substance from at least one individual reservoir ( 120 ) becomes passable. A method according to claim 20, wherein the substrate ( 110 ) is layered with the recesses and further comprising the step of: rolling up or folding the layered substrate ( 110 ).