WO2008049537A1

WO2008049537A1 - Use of magnetic cs capsules and/or micro-capsules for the treatment of aneurysms

Info

Publication number: WO2008049537A1
Application number: PCT/EP2007/008968
Authority: WO
Inventors: Andreas Spiegelberg; Peter Kirkpatrick
Original assignee: Apg Medical Ltd.
Priority date: 2006-10-23
Filing date: 2007-10-16
Publication date: 2008-05-02
Also published as: DE102006049837A1

Abstract

Magnetic capsules having a diameter of 100 nm to 5 μm are used for the treatment of malformations of blood vessels, particularly of aneurysms, by utilizing a magnetic field. The capsules comprise nanoparticles exhibiting super-paramagnetism.

Description

Use of magnetic CS capsules and / or microcapsules for the treatment of aneurysms

The invention relates to the treatment of malformations of blood vessels and in particular of aneurysms using agents that can be temporarily held by means of a magnetic field at the site to be treated.

Attempts to treat aneurysms and other malformations of blood vessels with such agents have been described in the prior art.

Various malformations of blood vessels can be treated by permanently closing the malformed area. An example of such a malformation is

an aneurysm, which is a permanent, abnormal, blood-filled pouch of a blood vessel. An aneurysm may be congenital or the result of a disease. Aneurysms typically have thin walls that can rupture. Aneurysms occur in the head and in other parts of the body. When the wall of an aneurysm breaks, it causes bleeding. If such hemorrhage occurs in the brain, there is a risk that the surrounding tissue will be permanently damaged. The bursting of an aneurysm can also result in blood flow in the blood vessel downstream of the aneurysm being compromised for a long time, resulting in death in the worst case.

Another example of vascular malformation is arteriovenous malformation (AVM). This is a typically congenital malformation consisting of a non-healthy vessel connecting an artery and a vein. Such a malformation causes arterial blood to prematurely drain into a vein and become unavailable for the supply of organs in the artery downstream of the malformation.

Methods are known for the surgical treatment of such malformations and in particular of aneurysms. Thus, aneurysms in the head are preferably treated by "cliffs". In this case, a resilient clamp made of steel or titanium is placed on the neck of the aneurysm, whereby the aneurysm is completely closed. While this surgical technique is well controlled, it is highly invasive and therefore disadvantageous.

Furthermore, methods for treatment by means of a catheter are known. In doing so, bodies or substances pass through a catheter, from a peripheral vessel to the aneurysm is inserted into the aneurysm. The body or substance causes a foreign body reaction in the form of clot formation. As a result, the aneurysm is completely filled by the clot and the body. The malformation is cured.

According to such an approach, helical or spiral wire bodies are inserted into the aneurysm. These can be inserted in stretched form through the catheter. In the aneurysm, they then form a ball that can not escape from the aneurysm.

In another approach, attempts have been made to introduce liquid substances into the aneurysm through a catheter that either cure in the aneurysm or form a thrombus together with existing blood, thereby filling and occluding the aneurysm. The problem is that the substances must not swim with the blood stream in the vascular system, otherwise they can cause irreparable damage in the vessels.

Attempts have also been made to use such substances to occlude the arteriovenous malformation. However, it has proved to be particularly difficult to prevent the floating with the blood stream into the vascular system, since in the existing due to the malformation vessel between the artery and vein regularly a relatively high flow rate of the blood prevails.

The use of flowable agents has certain advantages over the use of, for example helical or spiral wire bodies in the treatment of vascular malformations. The flowable agents are able to fill the malformation evenly. Also, it is generally easier to introduce fluid agents into an aneurysm than a or several discrete objects such as helical or spiral wire bodies.

In order in particular to prevent the floating of the flowable substance in the time between the exit from the catheter and the hardening or the formation of the thrombus, it has been proposed to create a substance mixture with magnetic properties and then hold this with the aid of a magnetic field at the site of action until the substance mixture has cured or the thrombus has formed.

In WO 00/54823 a magnetic means for the magnetic placement in a vascular malformation is described, which should be suitable to permanently close the defect. The composition comprises a mixture of polymer, solvent, adhesive and magnetic particles. As magnetic particles are preferred iron particles, as they are also used as dietary supplements for the treatment of iron deficiency. The iron particles preferably have a diameter between 1 and 10 microns. Other suitable magnetic materials besides iron include iron oxide (Fe ₃ O ₄ ) and nickel. It is described that particles of 99.97% pure iron with a particle size of 1 to 3 microns, when they come into contact with the oxygen in the blood, with the formation of iron oxides (FeO or Fe ₂ Oa) rust. The rusting causes the magnetic property of the iron particles to be lost. According to WO 00/54832 ferromagnetic particles are used as magnetic particles.

WO 02/068051 discloses a curable material which can be magnetically guided and held and which is intended to occlude vessel malformations. The material is a mixture of prolamine, ethanol, a material with magnetic susceptibility and a contrast agent. The preferred material with magnetic susceptibility is Fe ₃ O ₄ , So magnetite, which should be used in powder form. The largest diameter of the magnetite particles should be less than about 5 microns.

According to the two aforementioned documents relatively large particles of ferromagnetic material such as magnetite are used. Even in the earth's magnetic field, such particles can become magnets that attract and aggregate each other. When ferromagnetic particles enter the bloodstream, they are extremely dangerous because they can clump together in the small capillaries and block them.

In WO 03/051451 a means is described that can be magnetically guided or held. The agent comprises a plurality of coated magnetic particles. Each particle in turn comprises at least one core of a material that reacts to a magnetic field. Furthermore, each particle is at least partially coated with a material that does not react to a magnetic field. The nuclei of these particles have average diameters between about 5 nm and about 1000 nm. The use of the aneurysm treatment agent is described. The one or more cores of material that experiences forces in a magnetic field should be of reasonable size. However, larger magnetic particles tend to aggregate in undesirable forms upon application of a magnetic field. This tendency to agglomerate in undesirable forms is smaller for smaller particles. However, smaller particles would have the disadvantage of increasing the viscosity of the composition, as a larger number of particles would be required to achieve the desired forces in a given magnetic field. Coated particles are described which have sizes down to 10 nm. Magnetic cores made of a permanent magnetic material are preferred. As examples for the material of the cores magnetite is called among other things. It is stated that most superparamagnetic and paramagnetic alloys and various iron-containing mixed oxides are suitable. It is discussed that a compromise must be found on the size of the coated magnetic particles. The particles must not be too small so that the viscosity does not become too large. On the other hand, the particles must not be too large to remain in suspension when used in a liquid medium.

WO 03/051451 also describes coated magnetic particles in which the core comprises a large number of magnetic particles. According to this alternative, magnetic particles with diameters between about 2 nm and about 300 nm are embedded in a coating material. The magnetic material may be magnetite, as with the mononuclear particles. In both the mononuclear and polynuclear particles, the coating material is preferably a curable material. In the embodiments, magnetite particles are coated with chitosan.

The agents described in WO 03/051451 are unsatisfactory in terms of their suitability for the treatment of malformations of the vascular system and in particular of aneurysms. For very small particles, on the one hand the viscosity of the agent is too high or on the other hand, the forces are too small for a given magnetic field. For larger particles is expressly stated that these spontaneously accumulate in unwanted forms in the magnetic field.

The object of the invention is to overcome the above-mentioned disadvantages of the prior art. This object is achieved by the use specified in claim 1 of CS capsules and / or microcapsules. As the terms are used in the present invention, a CS capsule has a shell enclosing a core, whereas a microcapsule has a shell enclosing a cavity. In the case of the microcapsule, however, the cavity may in turn be filled again, but not with a solid core. The term "capsule" in the context of the present invention may refer to both CS capsules and microcapsules.

The capsules used according to the invention have a largest diameter of 100 nm to 5 μm. Essentially all capsules are said to have diameters within this range. If capsules with a diameter of more than 5 μm were to swim down into the vascular system, there could be a risk of blockage of capillaries. On the other hand, particles with a diameter of less than 100 nm are usually too small to achieve sufficiently high forces when applying a magnetic field. In principle, however, particles with a maximum diameter of less than 100 nm can be tolerated during use rather than particles with a maximum diameter of more than 5 μm.

For spherical particles, there is only one diameter. It is different with particles in the form of an ellipsoid of revolution. In this case, the largest diameter of the long axis corresponds to the ellipse. For irregularly shaped particles, the largest diameter is to be understood accordingly.

At the core of the CS capsules or in the cavity of the microcapsules are nanoparticles containing superparamagnetism. Superparamagnetism is a magnetic property of nanoparticles known to those skilled in the art. Superparamagnetism can be described using the example of magnetite, if the course of remanence or coercive force is ner, isolated particles as a function of grain size considered. Larger magnetic particles are divided into magnetic domains by Bloch's walls. Therefore, for larger particles, remanence and coercivity are independent of particle size. If one reduces the particle size, one first comes into an area in which each particle consists of only one domain. Remanence and coercivity are significantly increased for these particles. If the particle size is further reduced to the size of nanoparticles, a decrease in remanence and coercive force towards zero is observed. Superparamagnetism is observed, which occurs when the thermal energy of the particles is greater than the energy of magnetic anisotropy. Thus, while the large ferromagnetic magnetite particles have a permanent orientation of magnetic moments through the formation of magnetic domains, the superparamagnetic nanoparticles are so small that domains no longer form. The thermal energy is therefore sufficient to prevent a permanent alignment of magnetic moments in the nanoparticles. When a magnetic field is applied, the magnetic moments of the superparamagnetic nanoparticles, however, align so that strong magnetism is observed. The forces observed in a given magnetic field are much higher for superparamagnetic material than for paramagnetic material.

In the case of the capsules according to the invention, according to a preferred alternative, the shell consists of a material which does not react to magnetic fields.

In the claims and the description is given as the preferred use of the "treatment of aneurysms". In the context of the invention, the purpose of use is to be understood that it also relates to the treatment of aneurysms on the treatment of other malformations of blood vessels, in an analogous manner with the same capsules can be treated. An example of such a further malformation is the arteriovenous malformation.

In the context of the use according to the invention, it is provided according to an alternative that the capsules are applied with a catheter directly into the vascular malformation and in particular the aneurysm. There they are temporarily held with the help of a magnetic field. After a while, the thrombus forms in the aneurysm from the capsules and blood. After formation of the thrombus, the magnetic field is no longer required.

According to a further alternative it is provided that the capsules are injected into a peripheral blood vessel. The injection site is preferably chosen so that they pass capsules through the bloodstream as directly as possible to the site of the vascular system where the aneurysm is located. When the capsules reach the neck of the aneurysm, they are directed by the magnetic field into the aneurysm and held there. As with the first alternative, a thrombus then forms in the aneurysm from the capsules and blood. Once the thrombus has formed, the magnetic field is no longer required.

It will be readily apparent to those skilled in the art that the use of the invention may be made in an analogous manner in the treatment of other malformations of the vasculature, such as the arteriovenous malformation.

Microcapsules of the type used according to the invention are known in the art. Reference is made to WO 99/47252, WO 99/47253 and DE 10 2004 013 637 A1. The disclosure of these documents is incorporated by reference in its entirety by reference. In particular, all information containing the Construction of microcapsules and CS capsules, the subject of the present description made. With regard to DE 10 2004 013 637 Al, it is pointed out that instead of the term "CS particles" used therein in the context of the present invention, the term "CS capsule" is used in a synonymous manner.

WO 99/47252 discloses capsules with a Polyelektrolytthül- Ie and a diameter up to 10 microns. It is disclosed the use of such capsules to include active ingredients selected from catalysts, in particular, enzymes, pharmaceutical agents, sensor molecules, polymers, dyes, crop protection agents, flavorings and gases. Capsules filled with superparamagnetic nanoparticles are not disclosed in WO 99/47252 nor in WO 99/47253.

In DE 10 2004 013 637 Al microcapsules are described in one embodiment, which are filled with magnetite nanoparticles. Due to the manufacturing process, these microcapsules have a cavity of 10 microns and including the shell has a diameter of more than 10 microns. For the use according to the invention for the treatment of malformations of the vascular system and in particular of aneurysms, these microcapsules of the prior art are significantly too large. Although DE 10 2004 013 637 A1 also refers in general terms to the use of the CS particles and / or microcapsules for the encapsulation of nanoparticles, in particular for the production of fluorescent or magnetic microcapsules for diagnostic or medical applications. However, an additional reference to the specific use according to the present invention for the treatment of malformations of the vascular system and in particular of aneurysms is not found in DE 10 2004 013 637 A1. As already stated, the capsule shell can have a structure as described in WO 99/47252, WO 99/47253 and DE 10 2004 013 637 A1. Although the shell can consist of a single layer. Preferably, however, it comprises several layers. Furthermore, it is preferred that the shell has polyelectrolyte molecules.

According to a preferred embodiment, the shell comprises a plurality of polyelectrolyte layers, and in particular alternating layers of cationic and anionic polyelectrolytes. As described in WO 99/47253 and DE 10 2004 013 637 A1, the shell can also comprise alternately charged polyelectrolyte and / or nanoparticle layers. The nanoparticle layers may comprise paramagnetic and / or superparamagnetic nanoparticles. Furthermore, the inside of the shell may have an additional layer that is different from the other polyelectrolyte layers.

With regard to the selection of the polyelectrolytes, reference is made in particular to WO 99/47252. The polyelectrolytes are generally polyacids, polybases or their salts.

By polyelectrolytes are meant, on the one hand, polymers having ionically dissociable groups, which may be constituents or substituents of the polymer chain. Usually, the number of these ionically dissociable groups in polyelectrolytes is so great that the polymers in the dissociated form (also called polyanion) are water-soluble. However, the term polyelectrolytes in the context of the present invention in the broadest sense, ionomers understood in which the concentration of ionic groups for water solubility are not sufficient, but have sufficient charges to enter into a self-assembly. However, it is not preferred to use ionomers. Preferably, the shell comprises "true" polyelectrolytes. Depending on the type of dissociation ible groups, polyelectrolytes are subdivided into polyacids and polybases. From polyacids arise in the dissociation and the elimination of protons polyanions, which may be both inorganic and organic polymers. Polyacids which are suitable according to the invention are polyphosphoric acid, polyvinylsulfuric acid, polyvinylsulfonic acid, polyvinylphosphonic acid and polyacrylic acid. Examples of the corresponding salts, which are also referred to as polysalts, are polyphosphate, polysulfate, polysulfonate, polyphosphonate and polyacrylate.

Polybases contain groups capable of generating protons e.g. by reaction with acids to form salt. Examples of polybases are polyethyleneimine, polyvinylamine and polyvinylpyridine. Polybases form polycations by the absorption of protons.

Suitable polyelectrolytes according to the invention are also biopolymers such as alginic acid, gum arabic, nucleic acids, pectins and proteins. Chemically modified biopolymers may be used, e.g. Carboxymethylcellulose, chitosan, chitosan sulfate and lignosulfonates.

It can be used linear or branched polyelectrolytes. However, the use of branched polyelectrolytes results in less compact polyelectrolyte multilayer films having a higher degree of wall porosity. To increase the stability of the shell, polyelectrolyte molecules can be crosslinked within and / or between the individual layers, for example by crosslinking of amino groups with aldehydes. Furthermore, amphiphilic polyelectrolytes, for example amphiphilic block or random copolymers having a partial polyelectrolyte character, can be used to reduce the permeability to small polar molecules. Such amphiphilic polymers consist of units of different functions. nality, for example an acidic or basic units and, on the other hand, hydrophobic units such as styrenes, dienes or siloxanes, etc., which may be arranged as blocks or randomly distributed over the polymer. By using copolymers that change their structure as a function of external conditions, the shells can be controlled in terms of their permeability or other properties. Copolymers having a poly (N-isopropylacrylamide) moiety, eg poly (N-isopropylacrylamide-acrylic acid, which change their water solubility as a function of the water temperature via the equilibrium of hydrogen bonds, which is accompanied by a swelling, are suitable for this purpose, for example.

By suitable choice of the polyelectrolytes, it is possible to optimally adapt the properties and composition of the polyelectrolyte shell of the capsules according to the invention to the use according to the present invention. In particular, in the case of layered polyelectrolyte shells, the composition of the sheaths can be varied within a wide range by the choice of substances during the layer construction. In principle, there are no restrictions with regard to the polyelectrolytes or ionomers to be used, as long as the molecules used have a sufficiently high charge and / or have the ability to bond with underlying layers via other types of interaction such as hydrogen bonding and / or hydrophobic interaction.

Suitable polyelectrolytes are thus both low molecular weight polyelectrolytes and macromolecular polyelectrolytes, for example polyelectrolytes of biological origin.

It is preferred that the shell is made of materials that can be degraded by the human or animal organism. With regard to CS capsules, it is accordingly preferred that in addition to the superparamagnetic nanoparticles, not exclusively material that can be degraded by the human or animal organism. This ensures that individual washed-out capsules can be eliminated. In addition, there is the possibility that the contaminants introduced with the capsules are also degraded within the thrombus, so that this consists in the long term substantially of the body's own material.

The superparamagnetic nanoparticles with which the capsules are filled consist of at least one metal oxide and / or at least one elemental metal. The metal oxide is preferably iron oxide, nickel oxide or gadolinium oxide. The elemental metal is preferably iron, nickel or gadolinium. Particularly preferred is magnetite (Fe ₃ O ₄ ).

The superparamagnetic nanoparticles have an average particle size of less than 100 nm, preferably less than 50 nm, more preferably less than 20 nm, and most preferably less than 10 nm. The average particle size of the nanoparticles can be determined by known methods such as light scattering. It goes without saying that limits also exist with regard to the range of the absolute sizes of the superparamagnetic particles. The upper limit for the absolute particle size is given by the fact that particles are to be excluded, which are so large that a permanent alignment of magnetic moments can be done by forming magnetic domains. The particles should therefore not be so large that they have ferromagnetic properties. The lower limit of the particle size of the nanoparticles is relatively less critical. In principle, however, the particles should be large enough that they are reliably retained by the capsule wall. A lower limit for both the average particle size and the absolute particle size is 1 nm. As stated above, the capsules can have a largest diameter of 0.1 μm to 5 μm. The largest diameter is preferably 0.4 μm to 2 μm, in particular 1 μm to 1.5 μm. This is not the mean diameter but the range of absolute diameters. This range of the absolute largest diameters can be determined by means of a representative sample or several samples using microscopic methods. Suitable spectroscopic methods are Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM).

In the case of the capsules according to the invention, the wall thickness of the shell is preferably 2 to 100 nm. As already mentioned, the mechanical strength of the shell can be increased by crosslinking within individual layers or intermediate layers.

It is preferred that the capsules be in monodisperse size distribution. A close monodisperse size distribution is particularly preferred. Size distributions with multiple maxima are not preferred.

In the cavity of the microcapsules, in addition to the superparamagnetic nanoparticles, there may also be a liquid phase. Both the CS capsules and the microcapsules are preferably used in the form of a suspension and in particular in a suspension in isotonic saline solution. The liquid phase in the cavity of the microcapsule may consist of the same liquid in which the microcapsule is suspended.

The core of the CS capsules may comprise a porous material in the pores of which are the superparamagnetic nanoparticles. The porous material may be, for example, alumina, zeolite, a non-zeolitic molecular sieve or a porous polymer. The porous polymer may be polystyrene. Alternatively, the core of the CS capsules may consist of a non-porous polymer matrix in which the superparamagnetic nanoparticles are distributed.

It is preferred that the capsules used in total are electrically charged in the same direction. Accordingly, either all capsules are electrically positively charged, or all capsules are electrically negatively charged. When the capsules according to the preferred embodiment are suspended in use in a liquid, the co-entire charge of the capsules contributes to keeping them in suspension. Since all capsules have the same electrical charges, there is electrostatic repulsion between the capsules, thereby avoiding clumping and settling. The electrical charge of the capsules may also help accelerate the formation of the thrombus to shoot the aneurysm.

According to one embodiment, it is preferred that the shell is made of water-soluble material. With regard to CS capsules, it is accordingly preferred that their core, apart from the superparamagnetic nanoparticles, consists of water-soluble material.

Within the ranges indicated, the size of the capsules according to the invention is chosen such that the magnetic forces are large enough in relation to the flow forces in the blood vessels to ensure guidance into the aneurysm. On the other hand, the size of the capsules is chosen so that they can also pass capillaries without clogging them.

Because the magnetic forces acting on bodies with a spherical body-related diameter of less than 100 nm with technically feasible devices, are not large enough compared to the flow forces exerted on them by the blood flow, the diameter of the capsules greater than 100 nm is selected according to the invention. If the capsules according to the invention have no spherical shape, then the minimum size is preferably chosen so that spherical particles of the same total volume would have a diameter of 100 nm.

As already mentioned, the capsules preferably contain magnetite nanoparticles. The diameter of the nanoparticles should be in a range of 1 to 100 nm. The nanoparticles should have no ferromagnetic properties but superpa- magnetic properties. Because many superparamagnetic nanoparticles are filled together in one capsule, the overall diameter of the capsule determines both the magnetic forces and the flow forces.

According to an alternative already mentioned above, the hollow bodies are suspended in physiological saline and injected into the bloodstream. A magnetic field is applied so that the magnetic forces acting on the capsules are directed into the aneurysm. Thus, when the capsules in the bloodstream reach the vascular system where the aneurysm is located, they are directed into the aneurysm by the magnetic forces.

According to the other alternative already mentioned above, the capsules can be injected directly into the aneurysm through a microcatheter. The microcatheter is preferably guided under X-ray control to the aneurysm.

The capsules accumulate in the aneurysm. Finally, the aneurysm with the capsules according to the invention is as far as possible filled with blood between the capsules. The surface of the capsules triggers coagulation of the blood component in the aneurysm. It forms a thrombus. This forms over time to tissue, and it comes to complete healing. With a suitable choice, the capsule material including the nanoparticles may be degraded over time either already in the thrombus or later in the tissue, so that the healed site is free of foreign material.

The invention will be explained in more detail with reference to an example.

example

One according to the von Krings et al. Artificial aneurysm in a rabbit was 1 cm below the skin in the region of the transition from the thorax to the neck.

On the skin above the aneurysm, at a distance of 1 cm from the aneurysm, a magnet of neodymium with an edge length of 2.5 x 2.5 x 1.25 cm was placed. The magnet is available from Webcraft GmbH in Konstanz under the name Q-25-25-13-N. It has a remanence of 1.26-1.29 T. The product of flux density and flux density gradient in the aneurysm determining the attraction was about 0.0025 T * 2 / mm.

There were provided capsules according to the invention, which had approximately spherical shape with a narrow size distribution. The diameter of the capsules was close to 1.4 μm. The shell of the capsules consisted of 5 layers. The capsules were filled with nanoparticles of magnetite.

A suspension of 10% by weight of these capsules in physiological saline was submerged by a microcatheter X-ray control is given directly into the aneurysm. The microcatheter is available from Boston Scientific under the name Excelsior 144189.

After half an hour an angiogram was made, and it was found that the aneurysm was almost completely filled and no longer flowed through.

Then the magnet was removed and after another half hour an angiogram was made again. It was found that the aneurysm was still almost completely filled and not perfused.

After 3 days, the aneurysm was removed and examined. It was almost completely filled with a mixture of thrombus tissue and the capsules according to the invention.

This example shows that the use according to the invention is in fact suitable for the treatment of malformations of the vascular system and in particular of aneurysms in humans and animals.

The required magnetic field strength can be generated by known methods and devices in the human body, e.g. with one of the devices as described in DE 103 40 925, WO 2002 062 196 or EP-I 547 540.

Claims

claims

1. Use of mangetic CS capsules and / or microcapsules, wherein

a CS capsule has a shell enclosing a core,

a microcapsule has a shell enclosing a cavity, and wherein

the capsules have a largest diameter of 100 nm to 5 μm, and

the core of the CS capsule and the cavity of the microcapsule contain nanoparticles that have superparamagnetism,

for the preparation of an agent for the treatment of malformations of blood vessels, in particular of aneurysms, using a magnetic field or for the treatment of malformations of blood vessels, in particular of aneurysms, using a magnetic field.

2. Use according to claim 1, wherein it is provided that the capsules are applied with a catheter directly into the malformation and in particular directly into the aneurysm and held there by means of a magnetic field, to be in the malformation and in particular in the aneurysm of the Capsules and blood has formed a thrombus.

3. Use according to claim 1, wherein it is provided that the capsules are injected into a peripheral blood vessel and by a magnetic field in the malformation and in particular in the aneurysm are guided and held there when they pass through the circulation in the place of a blood vessel at which the malformation and in particular the aneurysm is located, the capsules are held until the malformation and especially in the Aneurysm from the capsules and blood has formed a thrombus.

4. Use according to one of the preceding claims, characterized in that the shell comprises a plurality of layers.

5. Use according to one of the preceding claims, characterized in that the shell has polyelectrolyte molecules.

6. Use according to one of the preceding claims, characterized in that the shell comprises a plurality of polyelectrolyte layers.

7. Use according to one of the preceding claims, characterized in that the shell comprises alternating layers of cationic and anionic polyelectrolytes.

8. Use according to one of the preceding claims, characterized in that the shell comprises alternately charged polyelektrolyt- and / or nanoparticle layers.

9. Use according to any one of claims 6 to 8, characterized in that the shell additionally has on its inner side a layer which is different from the other polyelectrolyte layers.

10. Use according to one of claims 5 to 9, characterized in that the polyelectrolytes of polyacids, polybases and their salts are selected.

11. Use according to claim 10, characterized in that the polyacids are selected from the group consisting of polyphosphoric acid, polyvinylsulfuric acid, polyvinylsulfonic acid, polyvinylphosphonic acid and polyacrylic acid.

12. Use according to claim 10 or 11, characterized in that the polybases are selected from the group consisting of polyethyleneimine, polyvinylamine and polyvinylpyridine.

13. Use according to any one of claims 5 to 12, characterized in that the polyelectrolytes include alginic acid, gum arabic, nucleic acids, pectins, proteins and / or chemically modified biopolymers, namely carboxymethyl cellulose, chitosan, chitosan sulphate and / or lignin sulphonate.

14. Use according to one of the preceding claims, characterized in that the shell consists of materials which can be degraded in the human or animal organism.

Use according to any one of the preceding claims, characterized in that the nanoparticles having superparamagnetism consist of at least one metal oxide selected from the group consisting of iron oxides, nickel oxide and gadolinium oxide.

16. Use according to claim 15, characterized in that the nanoparticles which have superparamagnetism consist of magnetite.

17. Use according to one of claims 1 to 14, characterized in that the nanoparticles, the Superparamagnetis- have at least one metal selected from the group consisting of iron, nickel and gadolinium.

18. Use according to one of the preceding claims, characterized in that the nanoparticles having superparamagnetism have an average particle size of less than 100 nm, preferably less than 50 nm, in particular less than 20 nm and most preferably less than 10 nm.

19. Use according to one of the preceding claims, characterized in that the largest diameter of the capsules is 0.4 μm to 2 μm and preferably 1 μm to 1.5 μm.

20. Use according to one of the preceding claims, characterized in that the wall thickness of the capsule is 2 to 100 nm.

21. Use according to one of the preceding claims, characterized in that capsules are used with monodisperse size distribution.

22. Use according to one of the preceding claims, characterized in that there is a liquid phase in the cavity of the microcapsule in addition to the nanoparticles.

23. Use according to one of the preceding claims, characterized in that the capsules are used in the form of a suspension.

24. Use according to claim 23, characterized in that the capsules are used in the form of a suspension in isotonic saline solution.

25. Use according to one of the preceding claims, characterized in that the core of the CS capsule comprises a porous material in whose pores the nanoparticles are located.

26. Use according to claim 25, characterized in that the porous material is alumina, zeolite, a non-zeolitic molecular sieve or a porous polymer.

27. Use according to claim 26, characterized in that the porous polymer is polystyrene.

28. Use according to one of claims 1 to 24, characterized in that the core of the CS capsule consists of a non-porous polymer matrix in which the nanoparticles are embedded.

29. Use according to one of the preceding claims, characterized in that each capsule is electrically positively charged in total or each capsule is charged electrically negatively.

30. Use according to one of the preceding claims, characterized in that the shell consists of water-soluble material.

31. Use according to one of the preceding claims, characterized in that there is only water-soluble material in the core of the CS capsule except the nanoparticles.

32. Use according to one of the preceding claims, characterized in that the shell consists of material which does not react to magnetic fields.

33. Use according to claim 8, characterized in that the nanoparticle layers in the shell comprise paramagnetic and / or superparamagnetic nanoparticles.