WO2009010303A2 - Système d'administration de substances actives à un organisme, dispositifs d'utilisation d'un tel système et procédé de fabrication de tels dispositifs - Google Patents

Système d'administration de substances actives à un organisme, dispositifs d'utilisation d'un tel système et procédé de fabrication de tels dispositifs Download PDF

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Publication number
WO2009010303A2
WO2009010303A2 PCT/EP2008/005919 EP2008005919W WO2009010303A2 WO 2009010303 A2 WO2009010303 A2 WO 2009010303A2 EP 2008005919 W EP2008005919 W EP 2008005919W WO 2009010303 A2 WO2009010303 A2 WO 2009010303A2
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WIPO (PCT)
Prior art keywords
electrically conductive
plastic
implantable
magnetically conductive
conductive structure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/EP2008/005919
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German (de)
English (en)
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WO2009010303A3 (fr
Inventor
Heribert Stephan
Werner Kraus
Stephanie Kraus
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Neue Magnetodyn GmbH
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Neue Magnetodyn GmbH
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Publication of WO2009010303A2 publication Critical patent/WO2009010303A2/fr
Publication of WO2009010303A3 publication Critical patent/WO2009010303A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5094—Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • A61N2/002—Magnetotherapy in combination with another treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • A61N2/02—Magnetotherapy using magnetic fields produced by coils, including single turn loops or electromagnets

Definitions

  • a system for administering active ingredients to an organism devices for use in such a system, and methods of making such devices
  • the invention relates to a system for administering
  • active ingredients such as chemotherapeutic agents, antibiotics or suitable cell formulations, based for example on endothelial cells, there is the fundamental problem that they reach the target region or the site of action, for example an organ or an implant, such as a vascular prosthesis only in low concentration. So not only the target region with the active ingredients or cells in contact, but also healthy body cells with the administered active ingredients / cells in a concentration in contact, in which affects the healthy cells and can be permanently damaged under certain circumstances.
  • magnetic drug targeting drugs or cells are coupled to a paramagnetic or supperparamagnetic carrier.
  • nanoparticles can be used which have the required magnetic properties.
  • the area of the patient on which the active substances are to be concentrated is thus stored in a spatially variable magnetic field, a so-called called gradient magnetic field, arranged to concentrate the drugs or cells in the region of the target. This reduces side effects for other parts of the body as they come in contact with lower concentrations of the drugs or cells.
  • the invention is based on the object of making it possible to apply biologically active substances or cells, to concentrate these active substances or cells after their application and to locally synergistically enhance their action.
  • the invention consists in a system for administering drugs or cells to a target region in an organism, with at least one vibration generator, one the vibration generator electrically coupled coil assembly, at least one implantable in the region of a flowing body fluid device, which consists at least partially of magnetically conductive material, and means for supplying paramagnetic nanoparticles coupled therewith active ingredients in the flowing body fluid.
  • the magnetic properties of the implantable device cause a magnetic field generated by the coil assembly in the region of the implantable device to be distorted. As a result of this distortion, even when the externally applied magnetic field is homogeneous, a magnetic gradient field is generated.
  • the ferrofluid introduced into the flowing body fluid ie the paramagnetic or superparamagnetic nanoparticles with active substances or cells coupled thereto, can then be concentrated by the magnetic gradient field on the affected body regions.
  • the implantable device can be used, in particular, in regions of the human body through which body fluids flow, that is, above all in the bloodstream, in the bloodstream
  • Lymphatic system or in the genitourinary tract.
  • the particular low-frequency electromagnetic fields can increase the effectiveness of active ingredients and / or the differentiation of cells can be influenced.
  • chemotherapeutic agents are used as active ingredients.
  • chemotherapeutic agents is to be understood as meaning all chemically or naturally produced active substances which can have an effect in an organism, in particular any medicaments.
  • the present invention can be used in the field of chemotherapeutic tumor control by concentrating the chemotherapeutic agent at the site of the tumor, thereby allowing other body regions through the chemotherapeutic agent not or only slightly less than conventionally affected.
  • endothelial cells can be administered as cells which, by their local attachment to a surface of the implant, improve the flowability of the blood flowing through the implanted device, in particular by influencing specific coagulation processes.
  • angiogenesis is favored and the development of inflammation is suppressed.
  • the administration of combinations of chemotherapeutic substances with cells is also possible.
  • the implantable device has a carrier with at least one introduced or applied magnetically conductive structure.
  • any biocompatible device may be used as the carrier, which generally has no or only a negligible interaction with the externally applied magnetic field.
  • the introduced or applied magnetically conductive structures then impart to the implantable device the properties which lead to the advantageous distortion of the magnetic field and finally to the concentration of the substances supplied.
  • the magnetically conductive structure comprises a multiplicity of ferromagnetic or paramagnetic particles.
  • this is formed in such a way that the magnetically conductive structure is formed as at least partially connected net-like or spiral-shaped structure.
  • a net-like or spiral-shaped structure can likewise be introduced into or applied to a carrier and be firmly connected to it.
  • the implantable device is at least two parts, wherein a first part is a carrier and a second part is a magnetically conductive net-like or spiral-shaped structure.
  • a conventional implantable device can be used first, the magnetic properties are then mediated by joining with a magnetically conductive reticulate or spiral structure.
  • the net-like or spiral-shaped structure is formed from a metal-plastic compound.
  • the advantageous properties of plastic can be used, wherein the magnetic properties can be made available by the metal content.
  • the net-like or spiral-shaped structure comprises a plastic-coated metal wire.
  • the metal wire providing the magnetic properties must therefore Do not come into contact with body tissue if it is covered with a biocompatible plastic.
  • the spiral structure may be a spiral, wherein the spacing between turns of the spiral is substantially equal to a diameter of the metal wire. It is useful to use wire diameters in the range between 0.2 and 1 mm.
  • the carrier of the implantable device at least partially consists of a biocompatible plastic.
  • typical materials for implants such as PTFE (polytetrafluoroethylene) or polyurethane.
  • the implantable device carries an electrically conductive structure.
  • a low-frequency electromagnetic field can be induced in the electrically conductive structure of the implantable device, thereby generating electric fields and voltages in their environment.
  • an additive protection against dangerous infections can be achieved.
  • the transmission of the fields to the electrically conductive structure takes place according to the transformer principle.
  • the body region in which the implantable device is inserted is characterized by an extremely low-frequency, in particular sinusoidal, magnetic field having a frequency of approximately 1 to 100 Hz, preferably 4 to 20 Hz, and a magnetic flux density of 0.5 to 5 mT flooded, which is generated by the vibration generator in the coil coupled thereto.
  • These Extremely low-frequency electromagnetic fields penetrate the tissue largely lossless, including any clothing and dressings. In the electrically conductive structure, this induces electropotentials, which come into effect in the tissue adjacent to the implantable device. Overall, this reduces the risk of infection in the area of the implantable device due to its synergistic effect.
  • the treatment parameters electrical voltage, frequency, intensity, signal shape and treatment time can be defined by the specific programming of the vibration generator.
  • the electrically conductive structure is at least partially vapor-deposited on an outer surface of the implantable device.
  • the arrangement of the structure on the outer surface is particularly advantageous with regard to the ingrowth behavior of the vascular prosthesis.
  • the application of the electrically conductive structure can also take place in such a way that the electrically conductive structure is at least partially applied to an outer surface of the implantable device by a sputtering technique.
  • the electrically conductive structure may be arranged at least partially in the interior of the implantable device and inaccessible from the outside. It is particularly useful that the electrically conductive structure has the character of at least one electrical coil connecting at least two electrodes. In this way, the electrically conductive structure obtains a useful and responsive response to the coil shape with respect to externally applied alternating electromagnetic fields.
  • the present invention is formed in a particularly advantageous manner in that the with the
  • Vibration generator coupled coil assembly comprises at least one Helmholtz coil pair.
  • a Helmholtz coil pair is able to generate a largely homogenous magnetic field into which the organism with the implanted device is to be introduced.
  • the required gradient property of the magnetic field that causes the attachment in the target region of the paramagnetic or superparamagnetic nanoparticles with the drugs coupled thereto is then generated by the magnetic properties of the implantable device.
  • a nearly homogeneous magnetic field may also be generated by a solenoid coil.
  • the coil arrangement coupled to the oscillation generator comprises at least one Maxwell coil pair.
  • a Maxwell coil pair already generates an inhomogeneous magnetic field externally.
  • the magnetic properties of the implantable device causes an additional distortion of the magnetic field.
  • the transport phenomena of the paramagnetic nanoparticles can also be effected solely by the external, inhomogeneous magnetic field of a pair of Maxwell coils, so that, in principle, implantable devices without a magnetic coil can be used Properties in connection with the presently described therapy can be used.
  • the coil arrangement coupled to the vibration generator comprises at least one electromagnet with a one-dimensional wedge-shaped core. This also makes it possible to externally generate the required gradient field.
  • Vibration generator coupled coil arrangement is provided a further means for generating a magnetic field.
  • both the weak low-frequency electromagnetic field and the strong magnetic gradient field can be generated by the coil arrangement electrically coupled to the oscillation generator.
  • it can also be useful to decouple these functions and, in particular, to generate the gradient magnetic field by a separate device, for example a further coil arrangement and / or by one or more permanent magnets.
  • the invention is realized in an advantageous manner by providing a drug reservoir, which in particular serves to record paramagnetic nanoparticles with active ingredients coupled thereto.
  • Drug reservoir forms insofar another system component that can be arranged outside the organism or else implanted into the organism.
  • the implantable device is a vascular prosthesis.
  • the wall of the vascular prosthesis carries the described magnetically conductive and / or electrical electrically conductive devices, which are integrated into the wall and / or applied to one or both of the surfaces of the wall.
  • the implantable device is a catheter. Since the active ingredients can be introduced into the organism via the catheter, a localization can already be achieved during the delivery, which is then intensified by the magnetic gradient field.
  • the implantable device is suturing material for tissue fixation or fixation of a biomaterial.
  • a heart valve can be fixed by sutures with magnetic properties, whereby z. B. the deposition of bacteria and germs can be prevented.
  • the suture fixes a device implanted in the region of a flowing body fluid and consisting at least partially of magnetically conductive material.
  • a vascular prosthesis according to the invention with a magnetically conductive component can be implanted with this suture.
  • the suture is a plastic thread with incorporated magnetically conductive material.
  • the suture may also be useful for the suture to be a delta-ferrite metal thread.
  • the magnetically conductive material is part of a secondary device for acquiring measured values in or on an organism, wherein the impedance of the secondary device depends on a state of a tissue surrounding the implantable device, that the coil arrangement electrically coupled to the oscillation generator
  • An organismally placeable primary device for generating an alternating electromagnetic field in the region of the secondary device is in an implanted state and that an organism-external evaluation device for capturing and evaluating measured values can be placed, which depend on the impedance of the secondary device.
  • Coronary heart disease is the leading cause of death in the industrialized world. More than 1.5 million interventions are being carried out worldwide each year to dilate narrowed or occluded vessels.
  • Such interventions include, for example, percutaneous transluminal coronary angioplasty (PTCA).
  • PTCA percutaneous transluminal coronary angioplasty
  • vascular prostheses so-called stents
  • stents are implanted at the same time.
  • the success of these measures is often called into question by the high probability of restenosis.
  • restenosis occurs within six months of intervention, that is, reocclusion of the vessels.
  • 25,000 patients had to be re-operated in 2000, which resulted in costs of around 500 million euros.
  • the currently used diagnostic methods for detecting vascular changes are based on the detection of reduced blood flow or gross arterial wall changes by imaging techniques. In principle, these diagnostic methods can only show late stages of the changes.
  • the invasive administration of contrast agents often associated with imaging techniques may also lead to complications that may manifest in pain, perforation of the arteries, arrhythmias and, in the worst case, heart and brain infarcts.
  • Another problem associated with the implantation of a vascular prosthesis is infection. A high percentage of these infections lead to serious and life-threatening situations.
  • This interaction can be detected organism-externally in various ways, so that changes in the region of the secondary device, in particular of an implant, are detected on a non-invasive basis can be.
  • hyperplasias that is, excessive cell growth
  • stents can be detected inside stents, as well as the beginning of the formation of a biofilm on an implant.
  • the secondary device has an electrical resonant circuit whose impedance and resonance frequency depends on the state of the environment of the secondary device. If the externally generated alternating electromagnetic field meets the resonance frequency, this can be detected and evaluated by the evaluation device. If the environment of the secondary device changes, be it through cell growth, cross-sectional change in the vessel or biofilm formation, this has an influence on the impedance of the oscillatory circuit, which changes its resonance frequency. Consequently, the organism-external evaluation device can detect a change in the area of the implant and thus indicate an imminent complication.
  • the resonant circuit-forming electrically conductive means are applied to the implantable secondary device using thin-film technology.
  • the electrically conductive means comprise first electrically conductive means applied to the implantable secondary device, which form part of a resonant circuit, that an electrically insulating layer, which is applied to the electrically insulating layer, is applied to the first electrically conductive means second electrically conductive means are applied, which form a further component of the resonant circuit, and that the first electrically conductive means are contacted with the second electrically conductive means, so that the resonant circuit is formed.
  • the required components of a resonant circuit can be precisely attached to the implant.
  • inductance and capacitance of the resonant circuit can be varied.
  • the first electrically conductive means have an outer area with windings and an inner area with capacitive properties.
  • the secondary device has a measuring device that detects measured values that depend on the state of the environment of the secondary device, that the secondary device has a transmitting device that emits signals dependent on the measured values, and that a receiving device that can be placed outside of the organism is provided is, receives the signals emitted by the transmitting device and supplies to the evaluation device. While the previously described embodiments of the telemetric measuring concept on the variation of the resonance frequency of a
  • Resonance circuit based can also be provided to equip the secondary device with a measuring device that detects various sensors by sensors in the area of the device. This includes, for example, the pH in the region of the implanted device, the
  • the transmitting device may have at least one RFID transponder.
  • An RFID transponder is a device that can "send out” only its interaction with an evaluation device or a reading device realized by the receiving device.
  • the RFID transponder receives an electromagnetic high-frequency field, which is generated by the evaluation device or the reading device, in order to then change this as a function of information stored in the RFID transponder. This change is detected by the evaluation device or the reading device. Because of this compared to conventional active transmitters limited functionality of an RFID transponder, this is inexpensive and space-saving.
  • the invention can be developed in such a way that a readable information content of the RFID transponder can be changed as a function of measured values which are supplied by the measuring device.
  • different voltages are applied by the measuring device to the memory of the RFID transponder, these voltages reflecting the properties detected by the measuring device.
  • Different voltages can now cause the memory contents of the RFID transponder to be changed, so that ultimately the identifier transmitted by the RFID transponder to the evaluation device is also changed.
  • a plurality of RFID transponders are provided which can be activated or deactivated in dependence on measured values which are supplied by the measuring device.
  • non-writable transponders are sufficient.
  • One or more threshold value circuits, in which the measuring device and the RFID transponder are integrated, ensure that different RFID transponders are active or inactive depending on the voltage supplied by the measuring device.
  • the evaluation device can thus receive different identifiers depending on the voltage supplied by the measuring device, and thus also ensure on this basis that the corresponding information is transmitted to the organism-externally arranged evaluation device.
  • the invention furthermore relates to devices that can be implanted in the region of a flowing body fluid or, based on the telemetric measuring technique, can represent any desired implant, this device having the properties described above and being in particular a vascular prosthesis, a stent, a catheter, suture, an osteosynthetic agent or an endoprosthesis.
  • the invention furthermore relates to a method for producing a vascular prosthesis or a catheter, with the steps: preparation of a biocompatible plastic, storage or attachment of a magnetically conductive material. as in or on the plastic and providing the plastic with an electrically conductive structure.
  • the manufacturing method of the vascular prosthesis or the catheter can be developed such that permanent magnet particles are used as the magnetically conductive material, wherein the plastic is combined with the permanent magnetic particles in a casting process and the casting process is carried out at least temporarily in the presence of an external magnetic field.
  • the external magnetic field is radially oriented.
  • the deposition of the magnetically conductive material takes place by merging a carrier with a magnetically conductive net-like or spiral-shaped structure.
  • the plastic is provided with the electrically conductive structure by vapor deposition.
  • the plastic prefferably be provided with the electrically conductive structure by means of a sputtering technique. Furthermore, it may be advantageous that the provision of the plastic with the electrically conductive structure takes place after shaping of the shape of the vascular prosthesis.
  • the plastic is provided with the electrically conductive structure prior to molding the shape of the vascular prosthesis.
  • a method according to the invention can be configured such that it comprises the steps of applying first electrically conductive means to the biocompatible plastic which are to form part of a resonant circuit, applying an electrically insulating layer to the electrically conductive means, applying second electrically conductive means to the latter electrically insulating layer, which is to form another component of the resonant circuit, and contacting the first electrically conductive means with the second electrically conductive means, so that the resonant circuit is formed.
  • the first electrically conductive means have an outer region with turns and an inner region with capacitive properties.
  • the invention further relates to a method for producing a magnetically conductive suture, comprising the steps of: producing a plastic melt, introducing magnetically conductive material into the plastic melt and producing a thread by using a melt spinning method.
  • PVDF polyvinylidene fluoride
  • PA6 polyamide
  • Polyester polytetrafluoroethylene (PTFE) and terephthalate is used.
  • a magnetically conductive material from the group Fe 3 O 4 , Sr-ferrite, NdFeB, SmCo and AlNi-Co is used.
  • both soft magnetic and hard magnetic materials can be used.
  • magnetically isotropic and anisotropic materials can be used.
  • Fe 3 O 4 which assumes superparamagnetic properties above a certain particle size between 1 and 100 nm, is used as the soft-magnetic material.
  • hard magnetic materials Sr-ferrite, NdFeB, SmCo and AlNiCo are used, whereby the typical coercive field strengths of the hard magnetic materials are above 10 4 A / m.
  • the coercive field strength is in the range of 10 -1 to 10 3 A / m
  • the particle sizes are preferably, for example, for SR ferrite at 1 to 10 ⁇ m and for NdFeB between 100 and 400 ⁇ m.
  • the melting point spinning process is performed at least temporarily in the presence of an external magnetic field. This aligns the magnetization within the suture.
  • the vascular prosthesis in the simplest case has the form of a tube. This has, for example, a length between see 1.5 and 10 cm, a diameter between 1.0 and 6 mm and a wall thickness between 0.2 and 1.0 mm.
  • the hose consists of biocompatible elastic plastic, for example Teflon or polyurethane, into which a magnetically conductive substance, for example a ferrite, has been introduced during its production, for example by dispersing.
  • Embedded on the outside and / or the inside and / or in the material of the ferrite plastic tube are patterns of electrically highly conductive material, preferably vapor-deposited or sputtered on the outside.
  • These may take the form of coils which, induced by a weak external low-frequency electromagnetic field, generate and in particular distribute electric fields and voltages on the surface of the ferrite plastic tube. This improves the ingrowth behavior into the surrounding tissue and provides protection against dangerous infections.
  • This therapeutic effect has been demonstrated and published by applications of the Magnetodyn method according to Kraus and Lechner for more than three decades, wherein in the past, in particular heavy disorders of bone and wound healing, often as a result of resistive infections, were managed by the process.
  • active substances or cells in the surroundings of the vascular prosthesis are locally accumulated by magnetic targeting by means of paramagnetic or superparamagnetic nanoparticles as drug carriers in an external strong magnetic field.
  • the effect of magnetic drug targeting is enhanced by superimposing the strong magnetic gradient field on a weak low frequency electromagnetic field that synergistically enhances the action of the drugs or cells.
  • This synergistic effect can also be achieved by an alternating use of the static strong magnetic field and the low-frequency electromagnetic field.
  • Figure 1 is a schematic representation of a system according to the invention with a vascular prosthesis according to the invention
  • Figure 2 is a perspective view of a first
  • Figure 3 is a perspective view of a second
  • Figure 4 is a perspective view of a third embodiment of a vascular prosthesis according to the invention.
  • Figure 5 is a perspective view of a fourth embodiment of a vascular prosthesis according to the invention.
  • Figure 6 is a perspective view of a fifth
  • FIG. 7 shows a sectional view of an exemplary coil arrangement with a vascular prosthesis arranged in its magnetic field
  • FIG. 8 shows a sectional view of a further exemplary coil arrangement with a vascular prosthesis arranged in its magnetic field
  • FIG. 9 shows different systems for generating different magnetic field profiles
  • Figure 10 is a perspective view of an electromagnet for use in the present invention.
  • FIG. 11 is a schematic representation of suture material according to the invention.
  • FIG. 12 shows a further embodiment of a system according to the invention.
  • FIG. 13 shows a further embodiment of a system according to the invention.
  • FIG. 14 shows a secondary device for use in a system according to the invention.
  • FIG. 1 shows a schematic representation of a system according to the invention with a vascular prosthesis according to the invention.
  • a vibration generator 10 and a coil arrangement 12, 14, which is electrically connected thereto are provided, which in the present case consists of two coils arranged in parallel.
  • a tubular vascular prosthesis 16, in the wall of which magnetically conductive material is incorporated, is implanted in the body to be treated and arranged together with the body to be treated in the magnetic field of the coil arrangement 12, 14.
  • the vascular prosthesis 16 communicates with a drug reservoir 24 via a catheter 26 directly or indirectly via the bloodstream, wherein the drug reservoir 24 may be disposed outside or within the human body.
  • an electrically conductive structure 18, 20, 22 is arranged, which in the present Ausbowungsbei- play a coil winding 18 and through this coil winding 18 interconnected surface electrodes 20, 22 has.
  • the coil arrangement 12, 14, which is electrically connected to the vibration generator 10, can be provided for generating homogeneous magnetic fields or else for generating gradient fields. If homogeneous magnetic fields are used, the magnetic gradient field required for the magnetic targeting is generated in a different manner, in particular by the distortion of the magnetic field due to the magnetically conductive material embedded in the vessel prosthesis. If the magnetic field gradients are already generated externally by the coil arrangement 12, 14, then in principle it is possible to work without local distortion of the magnetic fields, and this can also be used additionally.
  • Active substances or cells are introduced into the vascular prosthesis 16 from the drug reservoir 24 via the catheter 26, the active substances being coupled to paramagnetic nanoparticles.
  • the paramagnetic nanoparticles with the active agent can be located at one or more locations of the body.
  • the vibration generator 10 generates a low-frequency electromagnetic alternating field, which promotes the transport of the substances through the cell membrane. Another effect of the low-frequency alternating field is that the healing process of the vascular prosthesis is favored and in particular is not impaired by infections.
  • FIG. 2 shows perspective views of various embodiments of vascular prostheses. The details illustrated and discussed herein may equally apply to other implantable devices, such as catheters.
  • the vascular prosthesis according to FIG. 2 has a carrier 28, which preferably consists of a biocompatible plastic.
  • the carrier 28 is a magnetically conductive structure 30 in connection, which is here formed by a plurality of ferromagnetic or paramagnetic particles 32.
  • the magnetically conductive structure may be formed by permanent magnetic particles, as will be explained in more detail below with reference to FIG. These particles are incorporated, for example, in the biocompatible plastic of the carrier 28, or they may also be applied to the outer wall or the inner wall of the vascular prosthesis 16.
  • the carrier 28 of the vascular prosthesis 16 has a reticulated magnetically conductive structure 36. These can also be biokom- in the carrier patible plastic or be applied to the outside or the inside.
  • the reticulated structure 36 may be paramagnetic, ferromagnetic or permanent magnetic.
  • a spiral-shaped structure 38 is arranged on the support made of biocompatible plastic of the vascular prosthesis 16, wherein it may be ferromagnetic, paramagnetic or permanent magnetic.
  • the magnetically conductive structure 38 may be incorporated in the carrier 38, or it is applied to the outside or inside of the carrier 28.
  • the vascular prosthesis 16 according to FIG. 5 has a carrier 28 with embedded permanent-magnetic particles 34. This is illustrated in the sectional representation A, wherein it is also shown here that the permanent-magnetic particles 34 can be aligned in the radial direction. This can be achieved by applying a strong magnetic field in the radial direction during the dispersing of the biocompatible plastic with the permanent magnetic particles. With regard to the ferromagnetic particles, it is also possible to deposit these on the outside or inside of the vessel prosthesis 16.
  • the vascular prosthesis 16 according to FIG. 6 is in two parts.
  • the carrier 28 can be realized as a conventional vascular prosthesis, while the magnetically conductive structure in the form of a spiral 38 can be subsequently pushed onto the vessel prosthesis 28 which is finished in itself.
  • the spiral 38 may be paramagnetic, ferromagnetic or permanent magnetic. It can be made of a wire or of a metal-plastic compound.
  • Figure 7 shows a sectional view of an exemplary coil assembly disposed in the magnetic field of Gefäßpro ⁇ synthesis.
  • a Helmholtz coil arrangement 12, 14 is shown which generates a substantially homogeneous magnetic field in the area between the coils 12, 14.
  • the implantable device 16 arranged between the coils 12, 14 carries an electrically conductive structure 18 which connects two electrodes 20, 22 to one another.
  • FIG. 8 shows a sectional view of a further exemplary coil arrangement with a vascular prosthesis arranged in its magnetic field.
  • the coil arrangement 12 is a single solenoid coil, with a substantially homogeneous magnetic field being generated in the interior of the solenoid coil 12.
  • the implantable device 16 is arranged inside the solenoid coil 12, wherein a substantially spiral-shaped electrically conductive structure 18 connects two electrodes 20, 22 together.
  • FIG. 9 shows various systems for generating different magnetic field characteristics.
  • a Helmholtz coil pair 12, 14 with an implantable device arranged therein and an associated magnetic field course B along the axial extension X of the implantable device 16 are shown.
  • a corresponding arrangement of permanent magnets 44, 46 is shown, which generates a comparable magnetic field profile.
  • a Maxwell coil arrangement 12 ', 14' is shown in the lower area of FIG.
  • Helmholtz coil arrangement 12, 14 in the upper region of FIG. 9 differs in that the coils 12 ', 14' are in opposite directions and not in the same direction as the coils 12, 14 of the helmet. Holtzspulencrus are wound.
  • the associated magnetic field profile B along the axial extension X along the implantable device 16 is also shown.
  • the implantable device is equipped with a magnetically conductive structure.
  • the Maxwell coil pair 12 ', 14' generates a highly inhomogeneous magnetic field. The magnetic field gradient is thus already generated externally, so that the implantable device 16 can also be used without a magnetically conductive structure.
  • FIG. 10 shows a perspective view of an electromagnet for use in the context of the present invention.
  • the electromagnet with a one-dimensional wedge-shaped core 40 and a coil winding 12 shown here can serve for the one-dimensional field distortion.
  • a plurality of differently arranged electromagnets can be provided in order to produce a plurality of axially extending enrichment lines on a cylinder, in particular a vascular prosthesis or a catheter.
  • FIG. 11 shows a schematic representation of suture according to the invention.
  • the suture 42 contains magnetically conductive particles 42, for example ferromagnetic or paramagnetic particles.
  • the suture 42 can be used, for example, to place implants in the area of flowing body fluids, for example cardiac fluids. Fold from organic material to sew.
  • the suture 42 may be used to secure artificial implantable devices, particularly the implantable devices described in connection with the present invention, such as vascular prostheses.
  • FIG. 12 shows a further embodiment of a system according to the invention.
  • a secondary device 112 is implanted in an organism 110, that is in particular a living human body.
  • a coil arrangement 114, 116 is provided, which acts as a primary device and is suitable for generating an electromagnetic field in the region of the secondary device 112.
  • the coil arrangement may, for example, be realized by Helmholtz coils 114, 116, as shown, but also in other ways. It is essential that an electromagnetic field is present in the area of the secondary device 112.
  • the organism-external coils 114, 116 are powered by a functional current generator 118.
  • the secondary device 112 is now equipped with electrically conductive means 122, which form an electrical resonant circuit.
  • the impedance and the resonant frequency of this electrical resonant circuit depends on the state of its environment, ie in particular on the tissue state, the presence or absence of biofilms or any other parameters which reflect the conditions in the organism 110. If, for example, the frequency of the functional current generator 118 is set so that it corresponds to the resonant frequency of the resonant circuit formed by the electrically conductive means 122, this resonant state is determined by the evaluation device 120 monitored. Now shifts the resonant frequency of the organism-internal resonant circuit, so there are changes in the area of the secondary device 112, this is also detected by the evaluation device 120.
  • the secondary device 112 is a stent
  • this may indicate excessive cell growth.
  • the formation of biofilms on implants forming the secondary device 112 can be detected early. It is not absolutely necessary to operate the external alternating field with the resonant frequency of the resonant circuit; Other spectral components are also influenced by the changing conditions in the area of the secondary device.
  • FIG. 13 shows a second embodiment of a system according to the invention.
  • the state detection of the secondary device 112 here is not necessarily based on the monitoring of a resonance state. Rather, the secondary device 112 is equipped with a measuring device 134 and a transmitting device 136.
  • the measuring device 134 and the transmitting device 136 are supplied with energy via the electrically conductive means 122, which receive the electrically conductive means 122 from the electromagnetic field generated by the organism-external coil arrangement 114, 116.
  • the measuring device 134 may comprise any desired sensors in order to detect state parameters in the area of the secondary device 112.
  • the measuring device 134 usefully having an ion-sensitive field-effect transistor.
  • the of the transmitting device 136 transmitted signals are received by a receiving device 138, which forwards them to an evaluation device 120.
  • the devices described in connection with the previously described embodiments according to FIGS. 12 and 13, in particular the electrical means 122, the measuring device 134, the transmitting device 136, the receiving device 138, the evaluating device 120 and the functional current generator 118 can be implemented individually as well as in integrated circuits Shape can be realized.
  • the electrical means 122, the measuring device 134 and the transmitting device 136 are implemented partially or completely integrated.
  • the receiving device 138 and / or the evaluation device 120 can be completely or partially integrated with the functional current generator 118.
  • Figure 14 shows a secondary device for use in a system according to the invention.
  • the secondary device 112 carries electrically conductive means 122, which form an electrical oscillating circuit 124.
  • An outer region 130 of the electrically conductive means 122 has turns, that is, inductive properties, while an inner region 132 has capacitive properties.
  • the conductor structure realized with solid lines is first applied to the electrically insulating secondary device 112. This conductor structure is referred to as the first electrically conductive means 126. If the secondary device 112 is not insulated in any case, an insulating layer is applied to the secondary device 112 before the application of the first electrically conductive means 126.
  • first electrically conductive means 126 After applying the First electrically conductive means 126, an insulating layer is applied to the first electrically conductive means 126. Subsequently, second electrically conductive means 128 are applied to the insulating layer not visible here. In order to contact the electrically conductive means 126, 128 in such a way that an electrical oscillating circuit 124 is formed, two contacts are produced between the first electrically conductive means 126 and the second electrically conductive means 28, namely once at one pole of the parallel-connected condensers in the inner region 132
  • various thin film technologies can be used, which can also be used in combination, namely, for example physical (PVD) and chemical vapor deposition (CVD). Sputtering techniques can also be used.
  • the first measurement principle a change in the impedance or the resonance frequency of an implanted resonant circuit is evaluated in a simple manner. This method requires no active components in the organism, so that the problem of biocompatibility is reduced.
  • the external field preferably operates in a range between one kHz to one GHz, preferably in the range between 4 kHz and 120 kHz.
  • the second measuring principle is based on the coupling of electromagnetic energy in the secondary device, in which case the actual detection of the environmental condition is supported by active components.
  • the frequency can for example be chosen so that as much energy as possible is transmitted in the shortest possible time, or the frequency range used is determined on the basis of completely different criteria.
  • coil arrangements which are referred to as transducer coils, are integrated into these implants, and their poles are electrically connected to implant sections which act as electrodes.
  • An example of an osteosynthesis device making use of the described technique is disclosed in DE 10 2006 018 191 A1.
  • the femoral headcap implants described in 10 2004 024 473 A1 are examples of the use of the art in joint endoprosthesis. If, therefore, the organism-external coils are tuned to the frequency range of 1 to 30 Hz, preferably 10 to 20 Hz, required in Kraus and Lechner technology, then this technique can be used on the one hand and, on the other hand, it can also be used to operate the measuring device - Required energy are transferred to the system according to the invention.
  • Another example in which the present invention can be usefully employed because of a dual function of the external organism magnetic field is the area of drug targeting.
  • implants are equipped with magnetically conductive properties, so that a concentration of the magnetic field takes place in the region of the implantable device by external magnetic fields.
  • Is the implantable device in the area flowing body fluids for example in a blood vessel, it may be done by administering paramagnetic nanoparticles coupled with drugs or cells, a concentration thereof in the implantable device.
  • Both the first embodiment of the present invention with bare electrical resonant circuit and the second embodiment with active components can be combined with the drug-targeting technology by the organism Externally generated electromagnetic field on the one hand in the region of the implant for the purpose of the concentration of drugs or cells on the other hand, either monitored resonance frequency technology or provides energy for active components in the region of the implant.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un système servant à administrer des substances actives à un organisme, avec au moins un générateur d'oscillations (10), un agencement de bobines (12, 14) couplé électriquement au générateur d'oscillations (10), au moins un dispositif (16, 42) pouvant être implanté à proximité d'un fluide corporel en circulation, ledit dispositif étant constitué au moins partiellement de matériau magnétiquement conducteur, et des moyens (24, 26) servant à injecter des nanoparticules paramagnétiques auxquelles sont couplées des substances actives dans le fluide corporel en circulation. L'effet de vectorisation des médicaments est amélioré en interférant le champ de gradient magnétique intense avec un champ électromagnétique faible à basse fréquence qui améliore par synergie l'action des substances actives ou des cellules. Cet effet synergétique peut aussi être atteint par l'utilisation alternative du champ magnétique intense statique et du champ électromagnétique à basse fréquence. L'invention concerne en outre des dispositifs implantables (16, 42), un procédé pour leur fabrication ainsi que des systèmes et dispositifs de réalisation de procédés de mesure télémétriques.
PCT/EP2008/005919 2007-07-18 2008-07-18 Système d'administration de substances actives à un organisme, dispositifs d'utilisation d'un tel système et procédé de fabrication de tels dispositifs Ceased WO2009010303A2 (fr)

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DE102007033452.6 2007-07-18

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010006592A3 (fr) * 2008-07-18 2010-03-11 Neue Magnetodyn Gmbh Système d'acquisition de valeurs de mesure dans un organisme ou sur ce dernier, et procédé de fabrication d'un composant de ce système
WO2012022920A1 (fr) * 2010-08-19 2012-02-23 INSERM (Institut National de la Santé et de la Recherche Médicale) Dispositif implantable dans l'os temporal pour administrer un produit et prothèse auditive pourvue d'un tel dispositif.
US20140020474A1 (en) * 2009-08-26 2014-01-23 Ut-Battelle Llc Carbon nanotube temperature and pressure sensors

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2821376A1 (fr) * 2003-04-16 2004-11-04 The Children's Hospital Of Philadelphia Dispositifs a commande magnetique de distribution de medicaments et de genes
WO2005110395A1 (fr) * 2004-05-19 2005-11-24 University Of South Carolina Système et dispositif pour le ciblage magnétique de médicaments à l’aide de particules magnétiques porteuses de médicament

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010006592A3 (fr) * 2008-07-18 2010-03-11 Neue Magnetodyn Gmbh Système d'acquisition de valeurs de mesure dans un organisme ou sur ce dernier, et procédé de fabrication d'un composant de ce système
US20140020474A1 (en) * 2009-08-26 2014-01-23 Ut-Battelle Llc Carbon nanotube temperature and pressure sensors
US9476785B2 (en) 2009-08-26 2016-10-25 Ut-Battelle, Llc Carbon nanotube temperature and pressure sensors
US9494478B2 (en) * 2009-08-26 2016-11-15 Ut-Battelle, Llc Carbon nanotube temperature and pressure sensors
US9518885B2 (en) 2009-08-26 2016-12-13 Ut-Battelle, Llc Carbon nanotube temperature and pressure sensors
US9759622B2 (en) 2009-08-26 2017-09-12 Ut-Battelle, Llc Carbon nanotube temperature and pressure sensors
WO2012022920A1 (fr) * 2010-08-19 2012-02-23 INSERM (Institut National de la Santé et de la Recherche Médicale) Dispositif implantable dans l'os temporal pour administrer un produit et prothèse auditive pourvue d'un tel dispositif.

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