Method for drug delivery and drug delivery systems

p0001The invention relates to a device for release of a drug and a method for release of a drug and a medical implant comprising such a device.

p0002The apparatus and method are intended for inward and continuous drug release, in particular the local release of antibiotic agents. The active substance release systems in the form of spacers, as an active ingredient of spacers and also as an implant can be used. Basically, such methods and apparatus are not intended for ingestion, but are reacted with implanted into the body devices with containers of the drug. The invention here is concerned in particular with so-called spacers, which are used as an interim replacement for endoprosthesis in the body to fight an infection of the surrounding tissue.

p0003Cemented and non-cemented total joint endoprostheses (TEP) are state of the art in orthopedics. Unfortunately, there are a small number of early and late infections in TEPs. Infected TEPs generally make a currency-operation necessary. These exchange operations are divided into single-stage and two-stage operations. In the two-stage exchange operation the infected TEP is first removed, the debrided infected bone and soft tissue, and then used a spacer as a temporary placeholder. It usually industrially prefabricated spacers are used, which can include an antibiotic or individual from PMMA bone cement manufactured spacers, which formed without either, or using molds from the operator himself are high. These spacers can be manufactured specifically for the patient through individual doping of used PMMA bone cement with antibiotics, located according to the antibiogram of the infection to basically germs.

p0004Spacer remain mostly several weeks, often 6 to 8 weeks, the patients until the infection has calmed. The spacer is then in a second operation removed, debrided the adjacent tissue again and then the revision prosthesis is inserted, the cemented or cementless can be.

p0005In addition to the industrially produced PMMA spacers and the individually manufactured PMMA spacers which contain an antibiotic or several antibiotics, also spacers have been proposed which do not contain any antibiotics. These spacers contain cavities that can be filled by the medical practitioner with antibiotic solutions.

p0006In the <patcit id="pcit0001" dnum="US2010042214A1"><text>US 2010/042214 A1</text></patcit> Spacer are disclosed which contain at least one cavity, which is connected via channels with the outside of the spacer. The drug solution can be introduced into the cavity and then exits from the channel openings on the outer side of the spacer.

p0007A similar spacer was in the <patcit id="pcit0002" dnum="US2011015754A1"><text>US 2011/015754 A1</text></patcit> described having at least two tanks for holding active substance solutions. These tanks have openings through which the active ingredient solutions can be discharged into the environment.

p0008With the <patcit id="pcit0003" dnum="US2010217401A1"><text>US 2010/217401 A1</text></patcit> porous screws have been proposed that have a active agent reservoir in the interior, which is connected to the pores. Other very similar devices are already known from the writings<patcit id="pcit0004" dnum="US7794484B2"><text>US 7,794,484 B2</text></patcit>. <patcit id="pcit0005" dnum="US7255713B2"><text>US 7,255,713 B2</text></patcit> and <patcit id="pcit0006" dnum="US7300439B2"><text>US 7,300,439 B2</text></patcit> known.

p0009These spacers can be filled and other filled with drug solutions active ingredient carriers which are present in liquid dissolved form agents by simple diffusion step out.

p0010This has the disadvantage that it could lead to fluctuations in the release that the drug release is stopped earlier and that can lead to an asymptotic decrease in the release of active ingredients.

p0011The object of the invention is therefore to overcome the disadvantages of the prior art. In particular, an apparatus and a method is provided in which active ingredients over a period of up to several weeks can be released continuously and uniformly as possible also.

p0012The objects of the invention are achieved by a device for releasing a fluid agent comprising at least one cavity in which the fluid drug is contained, wherein in the device the water and a reducing agent are included which communicate with each other or with each other can be brought into connection, so that a gas produced by a chemical reaction of the water with the reducing agent in the device, and the gas is so with the fluid drug in operative connection, which pushes out the resultant gas pressure the fluid drug from at least one opening of the cavity from the device.

p0013Preferably it is provided that the resulting gas is hydrogen.

p0014According to one embodiment of the invention can be provided that the water is for the chemical reaction, a portion of a liquid aqueous solution which forms the fluid drug, wherein preferably the fluid agent is an aqueous solution comprising at least one pharmaceutically active substance, particularly preferably an aqueous solution comprising at least one antibiotic.

p0015This makes the assembly particularly simple and inexpensive to implement, as the active substance fluid, the blowing agent (gas) for expelling the fluid drug from the device holds simultaneously.

p0016Further, it can be provided that the reducing agent is a metallic surface, wherein preferably the metallic surface having a negative standard potential, more preferably the metallic surface magnesium, iron or alloys comprising contains magnesium and / or iron or consists thereof.

p0017Such surfaces corrode slowly so that a uniform and long-term release of the drug can be ensured with the construction.

p0018It can be provided that the reducing agent is magnesium, and a noble metal is forming an electrochemical cell, or said reducing agent is a mixture of a quickly and a slowly corroding metal corroding metal.

p0019With this variant, the release of the gas can be particularly good and long-term adjusted accurately.

p0020With a particularly preferred embodiment of the invention can be provided that at least one such mass of reducing agent and / or water in the apparatus is arranged such that an amount produced of gas that occupies at least 30% of the volume of the cavity, preferably at least 50 % of the volume of the cavity, particularly preferably at least 80% of the volume of the cavity.

p0021Through these quantities it is ensured that a sufficient portion of the drug is expelled from the device. Very particularly preferably, it is provided that such a mass is disposed of reducing agent in the device, that such a quantity of gas is produced which corresponds to 70% to 90% of the volume of the cavity. Then, the proper amount of reducing agent is just available, so that even with a longer retention of the device in the body is not unnecessarily large amount of gas is generated, which must be absorbed by the body.

p0022With a further particularly preferred variant of the invention may be provided that at least one cavity is at least partially formed by one or more capillary tubes in the device, which extend on one side up to an opening in the surface of the device, wherein preferably the cavities are formed by a plurality of at least regionally parallel capillary tubes.

p0023This structure is very simple and very secure. Through the capillary tubes will ensure that the surface tension of an aqueous solution contained ensures that first the aqueous solution from the capillary tube is driven, since the gas can not be pushed through the capillaries to the aqueous solution over. It is therefore in the present invention particularly preferably provided that the capillary tubes are capillaries. Preferably, the capillaries have a diameter of less than 500 .mu.m, particularly preferably of less than 200 microns.

p0024It can be provided that the reducing agent is disposed at the end opposite to the respective opening end of the capillary tube or capillary tubes, wherein the reducing agent is disposed in the cavity and is connected only via the opening of the tube with the surface of the device, preferably the fluid drug as an aqueous solution with the reducing agent is in contact.

p0025The gas is produced as on the desired side of the capillary tubes. In addition, the capillary tubes can preferably be coated on the side remote from the opening to the outside of the tubes with the reducing agent.

p0026According to an alternative, particularly preferred embodiment it can be provided that is arranged at least one opening of the cavity displaceable piston in the cavity in direction and the piston cavity into a first portion having at least one opening and a second closed or closable part divided, wherein in the first part of the fluid agent is arranged and in the second part of the reducing agent and water are arranged so that the resulting gas pressure in the closed, second part of the cavity of the at least drives the piston in the direction of an opening and thereby the fluid drug from the first part of the cavity by the at least one opening out of the device presses.

p0027With this construction, a greater amount of drug on the same space can be released slowly, than would be possible with the use of capillaries, since the cavity is considerably larger than the work space here in comparison to the external dimensions of the device.

p0028It can be provided that in the inner wall of the cavity an overflow is arranged, which in an initial position of the piston the first part and the second part of the cavity joins and the second part of the cavity comprises a shutter opening that is closable or closed by a shutter , so that the cavity in two parts with the same aqueous solution, which forms the fluid drug and the liquid water to the chemical reaction provides, can be filled through the locking opening, wherein the closure is constructed such that it when closing the shutter opening the piston in the cavity in the direction of the at least one opening to the overflow pushes over, so that the overflow channel the first and the second part of the cavity when the closure is fully inserted no longer connects and the piston the first and second part of the cavity gas-tight manner separated from each other.

p0029By this construction, the fluid drug can also be used as a source for the gas.

p0030It can in turn be provided that on the closure, at least one web and / or at least a hollow cylinder is arranged, which extends in the inserted closure in the first part of the cavity and during closure pushes the piston in the direction of the at least one opening to the overflow past ,

p0031Thus, the two cavity parts are easily and automatically on closing of the second cavity separable.

p0032According to a development of the invention it can be provided that on the closure, a thread, preferably an external thread is arranged and that the cavity in the locking aperture a mating thread, preferably an internal thread, so that the closure piston when screwing the closure in the direction of at least an opening to the overflow channel pushes past.

p0033In this way, a controlled advancing of the piston through the closure (or the cap or the screw cap) is possible. In addition, the thread can perform a sealing function.

p0034Furthermore, the invention can be provided that at least one valve member for gas discharge in case of overpressure to the second part of the cavity is arranged, preferably a bursting disc or a pressure relief valve on the second part of the cavity is arranged, wherein the valve member is preferably arranged in the piston so that at a sufficient overpressure in the second part of the cavity has an opening for the second part of the cavity in the piston is produced.

p0035This increases the safety of the device since such an undesirable overpressure can be at avoided.

p0036Devices of the invention may also be characterized in that the at least one cavity, in particular the capillary tubes of synthetic polymers and / or partially synthetic polymers or exist.

p0037These materials are for devices of the invention particularly useful and suitable.

p0038According to a preferred embodiment of the invention can be provided that the at least one aperture through a perforated body is closed, preferably closed by a perforated rubber body, the perforated body is arranged in the region at least one opening.

p0039In this way, premature unwanted leakage of the active substance fluids to be avoided from the apparatus.

p0040The objects of the invention are also achieved by a medical implant comprising such a device, wherein preferably, the medical implant is a Hüftspacer or a Kniespacer.

p0041Further, the objects of the invention are achieved by a method for releasing a fluid drug from a cavity of a medical implant, wherein a gas is generated by a chemical reaction of liquid water with a reducing agent, and the resulting gas pressure for expelling the fluid drug from at least one opening of the cavity is used.

p0042The inventive method is preferably implemented with a device according to the invention.

p0043In the process it may be provided as a gas that hydrogen is generated.

p0044The use of hydrogen gas as has the advantage that the water of the aqueous solutions can be used as the source for the gas, and so no additional gas sources are no longer necessary.

p0045It is also proposed. that a metallic surface is used as a reducing agent, preferably a metallic surface having a negative standard electrode potential is used, more preferably magnesium, iron or alloys comprising magnesium and / or iron is used as the metallic surface, wherein the gas, especially the hydrogen through corrosion of the metallic surface is generated.

p0046Such surfaces corrode slowly so that a uniform and long-term release of the drug can be ensured with the construction.

p0047It can be provided that magnesium and a noble metal is used as reducing agent and the gas is generated by an electrochemical reaction.

p0048These metals corrode with water sufficiently strong but slow enough to ensure a long-term uniform release of the active substance fluid. At the same time, these metals are safe for use in the human body for medical reasons.

p0049Alternatively it can be provided that a mixture of a quickly and a slowly corroding metal corroding metal is used as reducing agent.

p0050In this way the corrosion, and thus the flow rate of the fluid drug can be set even more accurately.

p0051Finally, it is proposed by the method according to the invention, that the liquid water which is used for chemical reaction, part of an aqueous solution which forms the fluid active agent, preferably an aqueous, pharmaceutically active solution is used as fluid of active compound, particularly preferably an aqueous solution comprising at least one antibiotic.

p0052According to the invention is also a process for drug release, which is characterized in that an aqueous solution of active substance is expelled from a cavity by hydrogen, resulting from corrosion of at least one metal or metal alloy when in contact with an aqueous electrolyte solution, wherein said at least one metal or at least a metal alloy is disposed at least in a part of the cavity.

p0053The invention is based on the surprising finding that it is possible with the inventive method and the inventive device, release agents continuously with an active transport mechanism over a period of up to several weeks, this transport mechanism is active at body temperature without the need for an external or internal energy source is necessary. The invention is based on the surprising discovery that magnesium, magnesium alloys, iron and iron alloys under the action of electrolyte solutions, and also body fluids, such as blood, corrode, and the by-product hydrogen is released, and the products of this chemical reaction (that is, hydrogen gas) as blowing agents for discharging a drug can be used in a cavity. The rate of corrosion depends on the metal used or of the metal alloy used, the surface-volume ratio of the metal or metal alloy and extends at a suitable building for a period of several weeks. This means that in the corrosion process continuously hydrogen is released, which is used for expelling the active ingredient from the cavity. When corrosion of magnesium produced Magensiumhydroxid which is non-toxic and completely safe. Magnesium is a natural part of the human organism. Iron corroded to form iron oxides. These are to be regarded as medically safe. Iron is a natural part of the human organism and is vital for humans. Therefore, these two metals for use in a device according to the invention and by a method according to the invention are particularly preferred.

p0054The basic idea of ​​the invention is based on the use inevitably released during the corrosion of metals, hydrogen as a drive for continuous release of active pharmaceutical ingredient solutions. A variety of water-insoluble active is present in the salt form and form after dissolution in water electrolyte solutions. Examples are for the antibiotic gentamicin sulfate, tobramycin, clindamycin and vancomycin hydrochloride. In the case of non-salt-like water-soluble or at least suspendable active substances of the active ingredient can be dissolved or suspended in medically conventional electrolyte solutions such as physiological saline or Ringer's solutions.

p0055According to the invention, and a variant of the invention is a device for release of active substance, which is characterized in that<ol><li>a) at least one kapillarförmiger cavity having at least one opening is arranged in the apparatus,</li><li>b) wherein the cavity is filled with an aqueous solution of active compound at least partially,</li><li>c) wherein the aqueous solution of active substance is at least one location with a metal or a metal alloy in contact,</li><li>d) wherein the metal or metal alloy is enclosed by a gas-tight casing and</li><li>e) wherein the metal or metal alloy is liquid permeable and gas-permeable by at least one opening of the envelope with the at least one capillary</li></ol>

p0056Cavity is connected, so that the resulting corrosion of the metal or metal alloy hydrogen and the aqueous drug solution can emerge at least one capillary hollow body only through the.

p0057This means that the fluid agent which may be an aqueous active compound solution or a drug suspension is first introduced into the capillary cavity, for example by aspiration. The drug solution comes into contact with the metal or metal alloy. The corrosion process begins and agitate continuously, hydrogen is released. This continuously drives the drug solution or drug suspension from the capillary cavity.

p0058An advantageous embodiment of the invention is that at least one such mass is disposed on metal or metal alloy in the apparatus, that a volume is released hydrogen through corrosion of the metal or metal alloy comprising at least 50 volume percent of the capillary cavity occupies at room temperature.

p0059satisfy smallest quantities of metal for the release of sufficient volumes of hydrogen. So is 1 mg of magnesium under standard conditions about 0.9 ml of hydrogen free. For continuous release hydrogen volumes are sufficient of a few milliliters. Therefore Metal quantities sufficient in the milligram range for driving a delivery system according to the invention.

p0060According to the invention is further that at least two capillary voids are present, said capillary bundles are particularly preferred. The capillary bundle or the bundle of capillary tubes can advantageously be arranged in tubular or any other shaped containers, at least one end of the capillary bundle for liquids and gases must be open. , when the capillary bundles are potted in the gas-tight container with a plastic material is particularly advantageous. The containers may be unilaterally closed by caps with thread or with lockable by detents caps, being located in the inside of the screw cap, the metal or metal alloy. It is also possible to combine two container having capillary bundles, wherein both containers are gas-tightly coupled to each other at each end, wherein said metal / metal alloy is arranged at the transition between the two capillary bundles. In the present invention, it may be also provided that the inside of the capillary cavities of the metal or metal alloys is coated as a reducing agent.

p0061It may be the invention also provides that the capillaries are made of synthetic polymers and / or partially synthetic polymers.

p0062According to the invention is further a device for the release of active ingredient, which is characterized in that<ul><li>a) a hollow body is placed in the apparatus, wherein the hollow body has at least one opening,</li><li>b) at least one overflow passage on the inside of the cavity is arranged in a distal part of the hollow body,</li><li>c) is arranged in a cavity in the axial direction of the hollow body displaceable piston,</li><li>d) a closure located at the distal end of the hollow body, which is formed at its proximal side as a tappet, and can be moved in the direction of the proximal end of the cavity by rotation or displacement,</li><li>e) wherein the piston is positioned initially so that the proximal cavity to the distal cavity located between the piston and the closure, is liquid permeable interconnected, and </li><li>f) wherein the distal cavity at least one body made of metal or metal alloy is, the corroded in contact with aqueous solution releases hydrogen.</li></ul>

p0063As the aqueous solution can present invention preferably an aqueous electrolyte solution used.

p0064This device works in such a way that the fully assembled apparatus, in which the piston between two openings or ends is arranged a transfer channel, it is first filled with the aqueous drug solution or drug suspension via the at least one opening (shutter opening) of the device. The two openings of the overflow channel connecting the proximal cavity to the distal cavity. The transfer port may be designed as simple axial groove. The aqueous drug solution or the aqueous suspension of active substance flow through the overflow past the piston from the proximal cavity in the distal cavity. In the distal lumen is the metal or metal alloy. The drug solution or the drug suspension comes into contact with the metal or metal alloy. Then, the closure by the user is moved by rotation or by displacement in the direction of the proximal end of the device. The closure is formed at its proximal end as plunger. This plunger moves the piston in the proximal direction. The piston passes over the proximal opening of the overflow channel. The distal cavity is thereby sealed gas-tight from the proximal cavity. In gas-tight distal cavity is at least a small part of the drug solution or the drug suspension and the metal or metal alloy. The corrosion starts. Is formed in the distal cavity continuously hydrogen, which moves the piston toward the proximal end of the device and thereby located in the proximal cavity drug solution or drug suspension of the at least one opening (proximal opening) pressed out continuously.

p0065An advantageous embodiment variant is that at least one opening element is arranged to the gas discharge under excess pressure, wherein a rupture disc or a relief valve are preferred which are preferably arranged in the piston, that in case of overpressure in the distal cavity connecting to the proximal cavity is prepared.

p0066It may further be advantageously provided that the proximal cavity has two openings which are arranged axially one behind the other, wherein the axial distance of the two openings is greater than the height of the piston. This can take the first opening of the piston at the end of Auspressbewegung, the remaining drug solution or drug suspension is pressed through the second opening. If the first opening is traversed by the piston, then the hydrogen can escape and an overpressure in the device can be securely prevented.

p0067According to the invention may further be provided that at least one such mass of metal or metal alloy is arranged such that a volume is released hydrogen through corrosion of the metal or metal alloy comprising at least 30 volume percent of the proximal cavity occupies at room temperature, preferably 50 percent by volume of the proximal cavity , more preferably 80 percent by volume of the proximal cavity. The proximal cavity corresponding to the second portion of the cavity.

p0068The two active ingredient release systems of the invention can itself as Hüftspacer as Kniespacer as local antibiotics carrier and also as a constituent of Hüftspacern, Kniespacern and are used by local antibiotic carriers.

p0069In addition, any other may be released in soluble or water-suspendable active substances with the novel drug delivery systems that can be formed in any shape.

p0070Embodiments of the invention are explained with reference to five schematically illustrated figures, without, however, limiting the invention. In which:<ul><li><figref idrefs="f0001">figure 1</figref>Is a schematic cross-sectional view of a device according to the invention;</li><li><figref idrefs="f0001">figure 2</figref>Is a schematic cross-sectional view of an alternative device according to the invention;</li><li><figref idrefs="f0002">figure 3</figref>Is a schematic cross-sectional view of another apparatus of the invention;</li><li><figref idrefs="f0002">figure 4</figref>Is a schematic cross-sectional view of a medical implant according to the invention; and</li><li><figref idrefs="f0003">figure 5</figref>Is a schematic cross-sectional view of a spacer according to the invention.</li></ul>

p0071<figref idrefs="f0001">figure 1</figref> shows a schematic cross-sectional view of a device according to the invention. The apparatus includes a base body 1 made of a polymer comprising a plurality of capillaries second The capillaries 2 may be made of a synthetic or partially synthetic polymer one, which are molded into the base body 1, either or are made of the same material as the base body 1 and produced in the body or with the base first The base body 1 is arranged in a housing 4 made of a biocompatible material.

p0072At one end of the housing 4 has an external thread 6 is provided, on which an internal thread is screwed a cap 7 eighth The cap 8 is also made of a biocompatible material. In the lid of the cap 8, a metal plate 10 made of magnesium and / or iron is arranged, which is connected via a flexible connection 12 to the cover cap of the eighth The threads 6, 7 are constructed such that when a complete unscrewing of the cap 8, the stop is chosen so to the housing 4, that forms a space 14 between the base body 1 and the cap eighth Instead of the elastic connection 12, the interior 14 may continue at this point, so that the metal plate 10 is substantially enclosed by the interior 14, or of its contents. The interior space 14 and the capillary 2 form a cavity 2, 14. In this cavity 2, 14 in the apparatus, so in the capillaries 2 and the inner space 14, an aqueous antibiotic solution is contained in the device.

p0073<figref idrefs="f0001">figure 2</figref> shows a schematic cross-sectional view of a similar construction. The structure comprises two basic body 1 having capillaries 2, which are arranged in a first housing 4 and in a second housing fifth The first housing 4 has an external thread 6 and the second housing 5 has an internal thread 7 and the two housings 4, 5 are screwed together. Between the two housings 4, 5, a metal plate 10 is arranged made of magnesium and / or iron or an alloy thereof, the part of the two housing 4, but may be 5, a separate metal plate 10 may be formed between the housings 4, 5 is arranged before they are screwed together. Between the base bodies 1 and the metal plate 10, the inner spaces 14 formed in each housing 4, 5. Preferably includes the metal plate 10 sealed to the walls at least one of the housing 4, 5, so that the inner spaces 14 are separated from each other. However, it is also possible that the inner spaces 14 are connected to each other through the metal plate 10 or channels on or in the housings 4, 5th Then in each space 14 of the same gas pressure is built up (refer to the explanation in the following description).

p0074The capillaries 2 and the inner spaces 14 form cavities 2, 14 in the apparatus that are at least filled with an aqueous solution of a pharmaceutically active substance. In both embodiments according to<figref idrefs="f0001">Figures 1 and 2</figref> the same process of the invention will be realized:

p0075The water in the aqueous antibiotic solution or the aqueous solution of the pharmaceutically active substance chemically reacts on the metal surface of the metal plate with the magnesium and / or iron, wherein the metal or metals to be corroded, whereby metal oxides are formed, and hydrogen gas is produced. The resulting hydrogen gas has a substantially greater volume under normal conditions, so that it expands in the space 14 and thereby pushes the aqueous solution from the capillaries 2 from the device. The chemical reaction of the corrosion of the metal plate 10 runs here so slowly that the aqueous solution is slowly pushed out of the capillaries 2 and therefore the device, the active ingredients over a long period gives evenly. The duration and the rate of hydrogen formation and thus the release of active ingredient of the device can through the choice of the reducing agent, that is, be set by the choice of the metals of the alloy and its surface finish.

p0076Below, further modifications of the invention based on the will <figref idrefs="f0001">Figures 1 and 2</figref> discussed. The capillary bundle 2 or the bundle of capillary tubes 2 are, for example in tubular containers 4, 5, wherein at least one end of the capillary bundle 2 for liquids and gases is open. it when the capillary bundles are 2 sealed in the container 4, 5 gas-tight with a plastic is particularly favorable. The container 4 can be unilaterally closed by caps 8 with thread 7 or lockable by detents caps 8, wherein in the inside of the screw cap 8 and the cap 8, the metal or metal alloy 10 is used as a reducing agent. It is also possible to provide two containers 4, 5 to be combined with capillary bundles 2, wherein both tanks 4, 5 are gas-tightly coupled to each other at each end, wherein said metal or metal alloy 10 is arranged at the transition between the two capillary bundles second In the context of the invention can also be provided that the inside of the capillary voids 2 is coated with metal or metal alloys. The chemical reaction in which the hydrogen is generated as a blowing agent for expelling the aqueous solution, so it must not only in the interior space 14 or run the interiors 14 but can also take place in the capillaries 2 themselves.

p0077With the <figref idrefs="f0002 f0003">Figures 3 to 5</figref> is presented by way of example a second embodiment of the present invention. <figref idrefs="f0002">figure 3</figref> shows a schematic side cross-sectional view of another device according to the invention, which comprises a hollow body 20 with a cylindrical cavity. At one end of the hollow body 20 a plurality of openings 22 are arranged in the walls of the hollow body 20, which connect the cavity of the hollow body 20 to the vicinity of the hollow body twentieth Prior to the inside of the openings 20 a perforated rubber sleeve 24 is arranged, which prevents an uncontrolled outflow of a fluid medium from the cavity.

p0078In the inner wall of the hollow body 20, an overflow 26 is arranged. At the height of the overflow 26, a piston 28 is disposed in the cavity of the hollow body 20 against the inner walls of the cavity of the hollow body 20 tightly seals with an O-ring seal 30 and thus the cavity of the hollow body 20 into a first part (in<figref idrefs="f0002">figure 3</figref> left) and in a second part (in <figref idrefs="f0002">figure 3</figref> right) divided. The two parts of the cavity of the hollow body 20 are connected in the illustrated initial position of the piston 28 via the overflow channel 26 with each other.

p0079The hollow body 20 is open on the side opposite the side openings 22 by a shutter opening with an internal thread. In the shutter opening a screw cap 32 is arranged, which has an external thread, via which the screw can be screwed into the locking aperture 32 of the hollow body twentieth At the front end of the screw cap 32, a seal 33, which seals the screw cap 32 and the shutter opening and thus the second part of the cavity of the hollow body 20 to the outside when the screw cap 32 is screwed into the locking aperture.

p0080On the front end surface of the screw cap 32, a plunger 34 is arranged, with which the piston 28 is pressed into the interior of the cavity of the hollow body 20 when the screw 32 is completely screwed into the hollow body twentieth Thereby, the piston 28 is inserted deeper into the interior of the cavity, so that the overflow channel 26 is then located entirely in the second part of the cavity, and thus the cavities not to each other. Around the plunger 34, a sponge 36 and including a metal plate 38 made of magnesium and / or iron or an alloy thereof, or are arranged in order.

p0081<figref idrefs="f0002">figure 4</figref> shows a schematic cross-sectional view of a medical implant according to the invention, analogous to the device of <figref idrefs="f0002">figure 3</figref> is constructed. The medical implant according to<figref idrefs="f0002">figure 4</figref> differs according to the device <figref idrefs="f0002">figure 3</figref> characterized in that at the front end of the medical implant or the hollow body 20 of the medical implant an additional opening 22 at the end face (in <figref idrefs="f0002">figure 4</figref> left) is arranged, which is also sealed by the perforated rubber sleeve 24th The medical implant has on the, the openings 22 the opposite end of the hollow body 20 is a plate 40.

p0082In the screw cap 32 of the in <figref idrefs="f0002">figure 4</figref> shown medical implant is disposed a Phillips, with the screw cap 32 is screwed into the cavity with a Phillips screwdriver. Except for these differences, the medical implant is to<figref idrefs="f0002">figure 4</figref> as the apparatus according to <figref idrefs="f0002">figure 3</figref> built up. The medical implant, for example, a pin, a screw or bolt to be, which is used to stabilize a bone in an implant or a spacer.

p0083<figref idrefs="f0003">figure 5</figref> shows a schematic cross-sectional view of a spacer according to the invention, the device according to the analogous <figref idrefs="f0002">figure 3</figref> or the medical implant according to <figref idrefs="f0002">figure 4</figref> is constructed. The spacer is formed by having its hollow body 20 a femur (thigh bone), which a femoral head ends 44th The spacer serves to be used as a replacement for a final prosthesis in a cavity in the body to fight an infection there.

p0084The embodiments according to <figref idrefs="f0002">Figures 3, 4</figref> and <figref idrefs="f0003">5</figref> all work on the same principle. The piston 28 is initially located in the initial position shown. The cap 32 is not used and thus the shutter opening (in the<figref idrefs="f0002 f0003">Figures 3 to 5</figref> right) open. An aqueous solution with a, for the application of Arz t mixed suitable combination of active ingredients is filled in the cavity of the hollow body 20 and flows via the overflow 26 in the front (first) part of the cavity. Subsequently, the screw cap 32 is screwed into the locking aperture. The piston 28 is inserted deeper into the interior of the cavity, moved past the overflow 26, and thereby separate the cavity into two parts.

p0085The apparatus according to <figref idrefs="f0002">figure 3</figref>, The medical implant according to <figref idrefs="f0002">figure 4</figref> or the spacer by <figref idrefs="f0003">figure 5</figref> are then ready for use and can be used as part of an operation in a patient's body. The water of the aqueous solution, which is also in the second part of the cavity reacts with the metal of the metal plate 38. This produces gaseous hydrogen. The sponge 36 is used to ensure wetting of the metal plate 38 with the aqueous drug solution. The sponge 36 attaches itself to fully with the aqueous solution.

p0086The hydrogen gas expands in the second part of the cavity (in the <figref idrefs="f0002 f0003">Figures 3 to 5</figref> right), and thereby drives the piston 28 in the direction of the openings 22. By the aqueous solution in the second part of the cavity between the openings 22 and the piston 28 (in the <figref idrefs="f0002 f0003">Figures 3 to 5</figref> left) 22 pressed out through the perforated rubber sleeve 24 and the openings of the device, the medical implant or the spacer. In this way a fluid drug is continually and uniformly released into the body of the patient.

p0087The water in the aqueous drug solution or the solution of the pharmaceutically active substance chemically reacts on the metal surface of the metal plate 38 with the magnesium and / or iron, wherein the metal or metals to be corroded, whereby metal oxides are formed, and hydrogen gas is produced. The resulting hydrogen gas has under normal conditions, a substantially larger volume, so that it expands in the second part of the cavity, while the piston 28 toward the openings 22 drives and thereby the aqueous solution to the first part of the cavity through the perforated rubber sleeve 24 and the openings 22 pushes. The chemical reaction of the corrosion of the metal plate 38 runs here so slowly that the aqueous solution is slowly pushed out of the openings 22 and therefore the device, the medical implant or the spacer, the active ingredients over a long period gives evenly. The duration and the rate of hydrogen formation and thus the release of active ingredient of the device can through the choice of the reducing agent, that is, be set by the choice of the metals of the alloy and its surface finish.

p0088Instead may provide only a small metal plate 38 and the inner wall of the second cavity, the second part of the cavity-facing side of the piston 28 and / or the entire end side of the screw cap 32 made of a metal or a metal alloy having a negative standard potential or with such a metal be coated or such a metal alloy.

p0089Preferably, in the piston 28 a pressure relief valve (not shown), so that in the event of an excessive overpressure in the second part of the cavity, a connection is created by the piston 28 in the first part of the cavity.

p0090In an alternative embodiment of the invention can also transfer port 26 are omitted. The two parts of the cavity are then separated from each other always. In the first part of the cavity a fluid agent is introduced thereto. Subsequently, the piston 28 is used. Thereafter, water or theoretically also another gas-generating blowing agent may be introduced into the second part of the cavity. Then, the second part of the cavity is closed. On the plunger 34 can be dispensed with in this embodiment. Even if this structure or the application is more complex, this has the advantage that different substances may be present in the two cavity parts for the respective application (effect of the active substances on the one hand and generating the gas on the other) especially tailored and thus are particularly suitable ,

p0091The features disclosed in the foregoing description, and the claims, figures and exemplary embodiments features of the invention can be essential to implementing the invention in its various embodiments both individually and in any combination.

LIST OF REFERENCE NUMBERS

p0092<dl id="dl0001" compact="compact"><dt>1</dt><dd>basic body</dd><dt>2</dt><dd>capillary</dd><dt>4, 5</dt><dd>housing</dd><dt>6</dt><dd>external thread</dd><dt>7</dt><dd>internal thread</dd><dt>8th</dt><dd>cap</dd><dt>10</dt><dd>metal plate</dd><dt>12</dt><dd>Elastic connection</dd><dt>14</dt><dd>inner space</dd><dt>20</dt><dd>hollow body</dd><dt>22</dt><dd>opening</dd><dt>24</dt><dd>Perforated rubber sleeve</dd><dt>26</dt><dd>overflow</dd><dt>28</dt><dd>piston</dd><dt>30, 33</dt><dd>O-ring / gasket</dd><dt>32</dt><dd>Screw cap / closure</dd><dt>34</dt><dd>tappet</dd><dt>36</dt><dd>sponge</dd><dt>38</dt><dd>Magnesium / iron flakes</dd><dt>40</dt><dd>plate</dd><dt>42</dt><dd>Phillips</dd><dt>44</dt><dd>Head of Femurspacers</dd></dl>