DE19654965A1 - Dispersible super-paramagnetic or ferromagnetic particles - Google Patents

Abstract

Dispersible particles (DP) comprise defined structured particles of super-paramagnetic (SPM) and/or ferromagnetic (FM) material, with a defined content of SPM and/or FM material and a defined crystal structure of the SPM and/or FM phase; and (possibly incomplete) electrostatic, steric or combined electrostatic/steric stabilisation layers. The stabilisation layers are commercially available or consist of mass-fractionated di-, tri- or multi-block copolymers (BCP). Alternatively DP are undefined structured particles, especially of SPM and/or FM materials, coated with BCP. The novel features are as follows. (i) The defined structured particles contain 0.001-99.999 (preferably 30-98) vol.% SPM or FM material and the crystal structure of the SPM or FM phase has a content of defects of 0.001-99.9 (preferably 0.001-10) vol.%. (ii) The defined structured particles are of metal, metal oxide or mixed metal oxide. (iii) DP include a BCP consisting of: (1) one or several first poly(oligo)meric and/or copoly(oligo)meric graft, side-chain or main chain blocks, which can undergo physical adsorptive, chemical covalent or other reciprocal action with (preferably colloidal, especially SPM and/or FM) particles, to provide stable anchoring of BCP on the particles in the sense of the steric stabilisation mechanism of colloidal dispersions; (2) one or several second poly(oligo)meric and/or copoly(oligo)meric linear or branched main chain blocks, which (in the case of stable dispersions, especially of colloidal, particularly SPM or FM, particles) are responsible for steric stabilisation in any dispersion medium, and optionally (3) one or several third poly(oligo)meric and/or copoly(oligo)meric graft, side-chain or main chain blocks, containing physically, chemically and/or otherwise reactive groups, which can react with substances, bodies or body parts added to dispersion media or contacted with the particles or their dispersions during the use of the (preferably colloidal, especially SPM and/or FM) particles (or their dispersions in polar or non-polar media) in industrial, biological, medicinal or veterinary applications.

Description

The present invention relates to dispersible particles, especially colloidal ones, and more specifically superparamagnetic and / or ferromagnetic dispersible particles.

In particular, the present invention relates to dispersible particles in which the particles made of superparamagnetic or ferromagnetic material in a non-polar or polar dispersion medium can be stably or unstably dispersed and the Particles of the superparamagnetic and / or ferromagnetic material various defined proportions of ferromagnetic material and defined degrees of crystallization point. Such particles can be of any size <1 nm, preferably 1-350 nm (at anisotropic geometries of the particles the largest dimensional dimension), and geometries exhibit.

The present invention further relates to a method for producing the aforementioned dispersible, defined superparamagnetic and / or ferromagnetic Particle.  

Finally, the present invention provides applications of the aforementioned dispersible, superparamagnetic and / or ferromagnetic particles in dispersions in nonpolar and polar media in technical, biological, medical and veterinary medicine Area.

In addition, the present invention relates to special, tailor-made di, tri and more block copolymers, characterized in that they consist of:

• (I) a first or more poly (oligo) mer and / or copoly (oligo) mer graft, side or backbone blocks that are physically adsorptive or chemically covalent or otherwise with particles, especially colloidal ones, especially with such superparamagnetic and / or ferromagnetic material, can interact and thereby a stable Anchoring the block copolymer with the aforementioned particles in the sense of steric Mechanism of stabilization of colloidal dispersions,
• (II) a second or more poly (oligo) mer and / or copoly (oligo) mer linear or branched main chain blocks, which - in the case of stable dispersions, in particular colloidal, especially such superparamagnetic and / or ferromagnetic particles - are responsible for the steric stabilization in the respective dispersion medium and (optional)
• (III) a third or more poly (oligo) mer or copoly (oligo) mer graft, side or main chain blocks in which physically and / or chemically and / or otherwise reactive groups are included during the use of the particles, in particular colloidal, especially of superparamagnetic and / or ferromagnetic particles, or their dispersions in non-polar or polar dispersion media in technical, biological, medical or veterinary field with substances or bodies or body parts can react, either deliberately inserted into the dispersion media or with which the particles or their dispersions come into contact, and methods for their manufacture.

The present invention further relates to applications of dispersible particles which contain only the aforementioned, tailored di, tri and more block copolymers, in nonpolar and polar dispersion media in technical, biological, medical and veterinary field.  

State of the art 1. Stable dispersions of colloidal particles

Colloidal particles are generally accepted definitions those whose extent in at least one dimension is in the range between 1 and 1000 nm lies. Such particles can either be broken by breaking larger ones - not colloidally daler - particles or through special growth processes in which they consist of low molecular weight Connections are synthesized. The use of mechanical processes is included only for the production of such particles with diameters in the upper range of the colloidal Size range possible, since the shredding and Grinding techniques do not allow the setting of particle sizes in the range <300 nm (Company brochures and verbal information from the Retzsch company).

The usual interaction forces of matter act between particles of colloidal size, the so-called Van-der-Waals interactions, which leads to the individual particles the attempt is made to break it down - and the resulting increase in free enthalpy by minimizing them in the form of (grape-shaped) aggregates. To maintain a permanent separation of the colloidal particles from each other, i. H. One has to produce thermodynamically metastable dispersions of colloidal particles Take action to effectively shield the attractive Ensure interaction forces (and the associated energies). According to the state of the art, shielding can be attractive Interactions between colloidal particles (apart from only a few special cases) either by applying (positive or negative) charges to the surfaces the particles or by applying spatial barrier layers, in the form of natural or synthetic polymer materials.

The shielding of surface charges, the so-called electrostatic stabilization mechanism, is based on the fact that the permanent surface charges give the individual particles either a positive or negative electrical surface potential. Since all colloidal particles (ideally) have potentials with the same sign, the individual particles repel each other. The mere existence of such a particle-particle repulsion is necessary for successful stabilization, but not yet sufficient. Only if the repulsive interaction enthalpies, which can be calculated from the surface potentials, are so great for all distances between the attracting particles that either the sum of attractive and repulsive interactions is positive or so slightly negative that it is in the range of thermal energy the particle lies, effective stabilization can take place by means of this stabilization mechanism. The repulsive enthalpy of interaction is the sum of an electrostatic and a chemical component. The electrostatic part is caused directly by the surface charge of the particles. The chemical component is due to the presence of adsorption layers of (opposite and equally charged) low molecular weight ions, so-called electrolytes. The electrolytes attach to the (oppositely) charged surfaces, since this causes a reduction in their free enthalpy. At the same time, they reduce the electrostatic repulsion of the previously uncovered particles. The adsorption layers of electrolytes on electrostatically charged surfaces of colloidal particles are called electrostatic double layers. Their destruction presupposes the redissolution of the adsorbed ions with increasing electrostatic repulsion. The latter is energetically unfavorable and therefore explains the stabilizing effect (chemical component) of the double layers for the corresponding colloidal dispersions. However, the thickness of the electrostatic double layers is very dependent on the electrolyte concentration. So is the thickness of the electrostatic double layer in a 1: 1 electrolyte at 25 ° C and different concentration z. B. (10 ^-4 mol / l) 30.4 nm, (10 ^-3 mol / l) 9.6 nm, (10 ^-2 mol / l) 3.0 nm and (10 ^-1 mol / l) 0.96 nm an electrostatically stabilized colloidal dispersion that its stability can be given in the one dispersion medium, in which the thickness of the electrostatic double layer is large enough to shield the attractive interaction energies, while in another dispersion medium (with the same electrolyte but a higher electrolyte concentration) is canceled. For practical matters it can be said that the electrostatic stabilization mechanism is only effective in cases in which the electrolyte concentration is less than 10-3 mol / l or the thickness of the electrostatic double layers is at least 20 nm.

An effective separation of colloidal particles by means of spatial barrier layers so-called steric stabilization mechanism, is carried out by a strong physical Adsorption or a chemically covalent anchorage of suitable natural or  synthetic polymers on the surfaces of the colloidal particles. "Physically strong" in context means that the resulting bonds are not short, medium and long term in the presence of the liquid dispersion medium, or in the presence of other adsorbable substances, detach from the surfaces of the colloidal particles (to let).

To be usable as a steric stabilizer, the natural or synthetic Polymers in general an at least copolymer structure, better a block copolymer structure and best have a graft copolymer structure, the one component of Copolymers for strong physical or chemical anchoring of the copolymers on the colloidal particles, while the other component, i.a. at least 90 mol% of a stabilizer molecule, the spatial barrier layer around the colloidal particles generated. Exceptions to this rule are homopolymeric stabilizers, which are both strong be physically or chemically covalently linked to the colloidal particles as well can form an effective spatial barrier. An example of the latter In the context of colloidal dispersions, substance classes are superparamagnetic and / or ferromagnetic materials, polyelectrolytes, d. H. polymerized, ionic diene molecules or conventional polymers in which all are present via polymer-analogous reactions Repeat units were ionized.

In order to produce optimally sterically stabilized colloidal particles, one is required complete coverage of the individual colloidal particles with block copolymers Adjust stabilizer molecules. The use of block copolymer stabilizer molecules ensures that there is no particle aggregation through interparticular bridge bonds (by means of the copolymeric stabilizer). The full coverage of the colloidal particles with the strongly physically or chemically anchored Stabilizer molecules prevent particle-particle aggregation due to the desorption of Stabilizer molecules from the particle surfaces or by lateral evasion of Stabilizer molecules against each other, whereby uncovered particle surface is exposed.

The steric stabilization of colloidal particles generally includes Case the separation of the individual colloidal particles at distances where the between the particles attractive Van der Waals interactions are practically eliminated. in the Colloidal chemistry is colloidal particles "infinitely wide" from each other  Cut. Therefore, only the solubility is important for the stability of such colloidal dispersions the stabilizing (spatial barrier) component in the liquid Dispersion medium crucial for the stability of such colloidal dispersions. It applies that optimal stabilities are observed in such liquid media in which the free Enthalpy of mixing of polymer and solvent medium both negative enthalpic as well as a negative entropic term. Other combinations of Mixing enthalpy and entropy lead to more or less unstable colloidal Dispersions with non-optimal "hydrodynamic" expansions of the spatial Barriers.

An effective, i.e. H. Sterically stabilizing, polymeric stabilizer cover is generally practical Case only exists when the "hydrodynamic" expansion of the steric Stabilization layer around the individual colloidal particles is at least 20 nm.  

2. Unstable dispersions of colloidal particles

Dispersions of colloidal particles in which the colloidal particles are either one Carry surface charge or are covered with natural or synthetic polymers, are unstable, d. H. they aggregate at a more or less high speed Let stand on a horizontal surface if (I) in the presence of poly outer layers on the colloidal particles, the solubility of the stabilizing com components of the stabilizers in the respective dispersion media with a positive free Enthalpy of mixing is associated, (II), in the presence of polymeric deck layer on the colloidal particles, the thickness of the spatial barrier layers produced the individual colloidal particle is not large enough to make the attractive Van der Waals Compensate for interactions, (III), in the presence of polymers Covering layers on the colloidal particles, covering the colloidal particles with stabilizing polymer is not complete, (IV), in the case of colloidal particles, which a Bear surface charge due to geometric asymmetries in certain areas (e.g. edge areas) a stabilizing electrostatic double layer is not formed and (V), in the case of colloidal particles carrying a surface charge too high an electrolyte concentration in the liquid dispersion medium leads to the formation of a stabilizing electrostatic double layer is prevented.  

3. Magnetism of matter 3.1. Slide, para and ferromagnetism

The magnetic properties of matter result from the elementary currents in atoms and molecules caused by the movement of the electrons around the atomic nucleus and their Self rotation are caused. Diamagnetism is due to the electron movement around the Atomic nuclei conditional. Paramagnetism is due to the self-rotation of the electrons. Atoms, molecules and molecular assemblies are paramagnetic if unpaired in them Electrons are included. Ferromagnetism is the property of paramagnetic substances the elementary elements within large crystalline atomic or molecular groups to couple magnetic dipoles in such a way that a permanent, rectified arrangement arises.

Depending on the magnetism of a special substance, it weakens slightly (diamagne table), it strengthens slightly (paramagnetic) or increases significantly (ferromagne table) the magnetic induction of (electromagnetic) coils. This means in the Terminology of the physics of magnetism: diamagnetic substances have a magnetic one Permeability <1 (or a negative magnetic susceptibility), paramagnetic substances have a magnetic permeability that is greater than 1 (or have a positive magne susceptibility) and ferromagnetic substances have a magnetic permeability <<< 1 (or a very large magnetic susceptibility). In addition, slide and paramagnetic properties of substances only in the presence of an external, magnetic field noticeable. The permanent coupling of the elementary magnetic dipoles of ferromagnetic materials, however, is as long as Absence of an external magnetic field), as not caused by an excessive thermal Energy of the elementary magnetic dipoles is destroyed (and into paramagnetic Behavior passes).

Since ferromagnetism is a property of crystalline atomic or molecular associations, it is also decisively influenced by the quality (quality) of the crystalline structure. Maximum ferromagnetism can only be observed in crystals without lattice construction errors.

3.2. Superparamagnetism

Superparamagnetic materials have properties that are paramagnetic Substances are characteristic, as are some of ferromagnetic materials. As the Paramagnetic substances have superparamagnetic substances no permanent (same directional) arrangement of the elementary magnetic dipoles in the absence of external ones acting magnetic fields. On the other hand, they have a similarly high magnetic susceptibility when an external magnetic field acts. They are also characterized by their existence crystalline structures.

Superparamagnetism occurs when the diameter of the crystalline areas in one normally ferromagnetic substance falls below a certain critical value.

Typical superparamagnetic substances are magnetite (Fe ₃ O ₄ ) and γ-Fe ₂ O ₃ . For both materials, the boundary between superparamagnetic and ferromagnetic behavior is around 30 nm (EV Groman et al., US 5,069,216 and US 5,219,554). However, since iron oxide crystals normally do not have a uniform size, the mean diameter for purely ferromagnetic iron oxide is considerably larger than the theoretical 30 nm. For example, γ-Fe ₂ O ₃ particles which are used for the production of sound carriers have a needle-like shape and sizes of 350 nm (length) and 60 nm (thickness / diameter). Other ferromagnetic materials used for the same purpose have lengths between 100 and 10000 nm. It can therefore be found that pure ferromagnetic materials have medium sizes which are many times larger than those which are usually observed with superpara magnetic materials.

The theoretical basis of superparamagnetism is found in thermal Destabilization of the permanent orientation of the elementary magnetic dipoles in the Crystal composite. The thermal energy of the elementary magnetic dipoles prevents them Alignment in the absence of external magnetic fields. After removing an outer The individual elementary magnetic dipoles are still acting magnetic field present, but they are in such a thermally excited state that they are cannot arrange in parallel (rectified); the crystals are not permanent magnetic.  

4. Dispersions of colloidal, superparamagnetic and / or ferromagnetic particles

Dispersions of colloidal, superparamagnetic and / or ferromagnetic particles, ie so-called ferrofluids, have already been described in a large number of documents. Patent applications in the area are e.g. B .:
US 5,023,072; US 5,064,550; US 5,104,582; US 5,124,060; US 5,135,672; EP 420 186; EP 421 249; EP 343 934; EP 131 796; EP 208 391; EP 250 236; EP 365 498; EP 328 497; EP 513 625; WO 90/15423; WO 91/02811; WO 91/15243; DE 41 01 869; DE 30 27 012; DE 31 36 449, DE 33 12 565; DE 38 06 657; DE 39 04 757; DE 36 19 746; DE 39 33 210; DE 41 42 405; DE 39 08 140; DE 39 07 844; JP 5239 489; JP 0 6061 032; JP 6 1281 023; SU 1764 087; JP 6 136 014; JP 0 5283 224; JP 0 5255 686; JP 05179 051; JP 0 5078 607; JP 0 5073 887; ES 204 91 84; DE 44 30 285; DE 43 27 225; DE 43 27 223; DE 42 13 513; DE 41 15 608; EP 580 878; US 4,810,401; DE 41 16 093; DE 35 20 210; DE 41 24 458; DE 35 16 885; DE 40 41 467; DE 37 14 783; DE 37 37 909; DE 44 07 338; DE 43 09 333; US 5,160,725; DE 37 09 851; DE 37 09 852; EP 284 549; WO 96/04017; DE 44 28 851; DE 41 17 782; EP 516 252; US 5,219,554; US 5,069,216; WO 88/00060; EP 600 529; EP 669 135; WO 94/04197; EP 673 655; EP 546 939; DE 41 30 268; EP 525 199; EP 707 856; WO 91/12025; DE 39 08 623; WO 91/01147; WO 91/01148; EP 414 287; DE 37 44 518; EP 516 198; DE 35 08 000; DE 35 90 398; DE 34 22 249; EP 186 616; WO 86/01112; EP 177 545; WO 85/04330; DE 30 26 868.

The syntheses for the production of colloidal superparamagnetic and / or ferromag netic materials with defined compositions and defined crystal structures is not yet being intensively examined [L. Hu and M. Chen, Mater. Chem. & Phys., 43 (1996) 213]. The manufacturing conditions for such defined compositions are unknown.

The following is based on relevant patent applications in the field of water-soluble colloidal dispersions of superparamagnetic and / or ferromagnetic particles the technique of producing and stabilizing dispersions of colloidal, superparamagnetic and / or ferromagnetic particles generally described. Of the contained reverse conclusion, the state of the total area of colloidal dispersions superparamagnetic and / or ferromagnetic particles based on that of aqueous colloidal dispersions of superparamagnetic and / or colloidal particles  describe, is permissible, since the latter dispersions only in the recent past have come into the focus of commercial and scientific research, therefore at a time when the latest state of the art of high performance superparamagnetic and / or ferromagnetic particles in non-aqueous Dispersions of the aforementioned type are included, was already known.

The colloidal particles of superparamagnetic and / or ferromagnetic substances described in the prior art are, in the vast majority of cases, oxide particles and mixed oxide particles of iron, e.g. B. Fe ₂ O ₄ and γ-Fe ₂ O ₃ . In this context it is important to note that occasionally e.g. B. in DE 44 30 285 A1, EP 546 938 A1 and DE 43 25 386 A1, it is claimed that in the preparation of the aforementioned iron oxides via the known precipitation process in an alkaline medium, a ratio of iron in the starting solutions of the iron salts must be ( III): Iron (II) ions of 2: 1 are present so that the desired iron oxide (Fe ₃ O ₄ ) is also formed during the precipitation. Such indications are of no value for the actual synthesis process of the oxide particles, since pure iron oxide is never formed when iron ions are precipitated in alkaline solutions. Rather, it applies (cf. HR Christians, Fundamentals of General and Inorganic Chemistry, Sauerländer - Salle, 1977, p. 644) that iron (III) salts lead to "gelatinous precipitation from highly hydrated Fe ₂ O ₃ " when precipitated. Iron (II) salts, on the other hand, precipitate in the form of iron (II) hydroxide [FeOH) ₂ ], which is immediately oxidized when air is admitted, producing iron (III) hydroxide (FeOOH). Thus, the precipitations generated are always more or less disturbed aggregates of water-containing Fe ₂ O ₃ , iron (II) hydroxide and iron (III) hydroxide.

EP 546 939 A1 describes colloidal dispersions of superparamagnetic metal and Metal oxide particles for NMR diagnostics. The individual superparamagnetic particles, consist of clusters of subdomain particles with a diameter of at most 7 nm, The subdomain particles are not yet superparamagnetic and adsorptive or covalent about polymerized organometallic monomers u. a. connected with each other. The size of the pure subdomain particle cluster is not specified. After being organic degradable polymers have been encased, they have sizes between 100 to 2000 nm. As far as a biological functionalization of the clusters takes place, it takes place via the (Statistical) copolymerization takes place during cluster formation or is achieved by direct Application of the biomolecules to the clusters achieved. The registration does not provide any information  about the quality of the crystal order in the subdomain particles and their metal oxide content, however, the precipitation of the iron takes place very quickly, so that the crystallization process of the metal oxide precursor (see above) can never have been optimal. Of the Metal oxide content should be the usual 50% (cf. DE 43 09 333 A1). As far as it is can be judged on the basis of the formulations, the total number of dispersions of superparamagnetic clusters described in no case around stable colloidal Dispersions, since adequate stabilization of the large clusters produced is not described.

EP 516 198 A2 describes electrostatically and sterically stabilized polymer / metal (oxide) Particles without giving any indication of the structural structure of the complexes generated. In any case, the manufacturing method involves the precipitation of metal ions (iron) in alkaline solutions in the presence of polymers. The presence of the latter in the Preparation solutions inevitably result in the emergence of only very small ones superparamagnetic particles because their growth process due to the coating with stabilizing polymer is terminated too early. The invention appears unbelievable in the claim that one can carboxyl group-containing and other anionic groups use containing polymers for the aforementioned purpose, it is a fact that Iron ions complex and form with any type of anionic group corresponding solutions fail. There are also doubts about the feasibility of electrostatically stabilized superparamagnetic colloids in physiological solution, especially when exposed to magnetic fields. Information about the quality of the Crystal arrangement and the content of metal oxide in the finished colloids are not made; however, the mixing of the iron salt solutions with the alkaline takes place Precipitants take place very quickly, leaving a catastrophically bad one Crystal growth process can be assumed. The metal oxide content should be in the usual 50% (see. DE 43 09 333 A1).

EP 525 199 A1 describes colloidal, superparamagnetic metal oxide dispersions based on of polysaccharides which are either prepared as described in EP 516 198 or in which the polysaccharide component after the synthesis of the metal oxide particles on this is grafted chemically. In addition, low molecular weight, monocarboxylic acids integrated into the complexes. The colloidal dispersions produced in this way are physiological Environment not stable. The way of the crystallization process to produce the Metal oxide precursor is not described in detail. The proportion of magnetic metal oxide  and the quality of the crystalline structure of the metal oxide particles remains unknown, the former lies however, probably with the usual 50% (cf. DE 43 09 333 A1).

DE 41 30 268 A1 describes colloidal magnetite dispersions which have a three-phase Have structure. They consist of the superparamagnetic core, a polymeric one Anti-agglomeration layer and a polymeric dispersion aid that the Water solubility improved. The colloids are said to be multicarboxylated functionalized polymer be present in the starting solutions of the metal salts. As before mentions such a constellation that Metal / carboxyl group-containing polymer complexes. So far this patent application is unbelievable. No information is given about the crystal growth process of the metal oxide Precursor, the degrees of crystallization achieved and the proportion of metal oxide in the resulting made of colloidal metal oxide particles. To this extent, a metal oxide content of 50% with an undefined crystal structure.

Massart et al. (DE 41 16 093 A1) describe electrostatically stabilized ferrofluids, which u. a. should also be stable in physiological solution. The authors have, however overlook the fact that in physiological solution there is no longer an electrostatic double layer is present, so the stability of the colloids can no longer be given. The production the superparamagnetic particle itself is not described, so it is also missing Indications of the crystal structure and the proportion of metal oxide.

Groman et al. (WO 88/00060 A1; US 5,069,216 and US 5,219,554 A1) describe in Principle of "normal" dextran magnetites, i.e. H. those in which the magnetite is present in the presence of Dextran u. a. polymeric stabilizers was precipitated. In addition, so-called magnetite Dispersoids, i. H. Larger (5-400 nm), lump-like magnetite particles that the Failure process arise directly at the drop-in point of the base, described. Latter should be electrostatically stabilizable and then dispersible in physiological solutions. It is interesting about this work that the authors (as the first ever) on the structure of the colloidal magnetite particles, that is, they describe the magnetite particles as those containing both magnetite and iron oxide hydrate. They also try that Oxide content in the resulting particles by an ultrasonic treatment, which follows particle synthesis takes place to increase. On the other hand, however, comes from the given Examples show that these inventors are in no way a defined crystal growth  have tried the metal oxide precursor. I.a. finds the precipitation of the iron ions very quickly instead of. The result is (forcibly) undefined magnetic nanoparticles. With View of special biological and / or medical applications of sterically stabilized For colloids there is the remark "the steric stabilizers can also be used for Functionalization with biological molecules can be used ". Furthermore, steric Stabilizers based on water-soluble silane polymers claimed to be covalent biological molecules (antibodies) are bound. The structure of these stabilizers will however not described.

EP 516 252 A2 and DE 41 17 782 A1 describe aqueous ferrofluids based on Fe ₃ O ₄ and γ-Fe ₂ O ₃ , which can be used for medical diagnosis and therapy. It is claimed that the superparamagnetic particles contained therein could be produced in the presence of an (anionic) polyelectrolyte (ie chondrotin sulfate; molecular weight unknown) by conventional precipitation and by means of a new process which enables precipitation in the neutral pH range. In general, the patent claim extends to steric stabilizers which are included in the class of glycosaminoglycans, in particular to those which are functionalized with biological molecules, the manner of functionalization not being described. However, it can be assumed that the functionalization takes place through statistical, polymer-analogous reactions. The authors call "normal" dextran magnetites medically inapplicable because they have too many harmful side effects. The way in which the colloidal particles of the superparamagnetic material are produced is described with absolute imprecision. With regard to the growth process of the metal oxide precursors, the comments "3N NaOH solution is added slowly" and "the finished magnetite is cleaned and autoclaved, which also accelerates the healing of any defects in the magnetite crystals". It can therefore be assumed that the crystal growth process is as undefined as that described in all previous patents.

Kresse et al. (WO 96/04017 A1 and DE 44 28 851 A1) describe in their applications Three-component particles that are optimized for medical use and as superparamagnetic material magnetite included. Such particles consist of a) one Core made of superparamagnetic magnetite (diameter <30 nm), b) a polymeric, sterically stabilizing primary coating and c) a low molecular weight or polymeric  Topcoat, which is physically adsorbed on the primary coat, if necessary with the help of (low molecular weight) adsorption mediators. The top coat determines that biological functionalization of the particles, d. H. the possibility of tissue-specific Commitment. The primary coat is for the stability of the colloidal particles in the physiological Medium responsible. The primary coated magnetite particles are manufactured via a "one-pot synthesis" in which the magnetite precursor synthesis in the presence of stabilizing polymer takes place. Interestingly, it is also said here Polymers containing anionic groups could be used in this context will. Furthermore, the stabilization with molecular weights of the polymers used, which in Range <15000 may be possible. That both are nonsensical has already been mentioned above documented. As for the manufacture of the metal oxide precursors and their conversion into As far as crystalline metal oxide is concerned, the authors' level of knowledge about possibilities Generate defined crystal structures and metal oxide levels, unclear. On the one hand, "a lot on the importance of the crystal structure of magnetite for the particles to be produced spoken (e.g. "The general production of the iron containing cores aims at a to synthesize magnetite-like crystal lattice "and" The formation of Magnetite preferred "), on the other hand documents the" wild "spilling of the Iron salt solutions and the alkaline precipitants that are only very inadequate here Information regarding a defined crystal growth can be present.

Pilgrin (EP 284 549 A2, DE 37 09 851 A1 and US 5,160,725 A1) describes in its Patent applications for colloidal particles of superparamagnetic metal and metal oxide materials. The production of the latter particles can be carried out with all of the prior art Procedure. However, it is significant that the present inventions in no case the synthesis of defined crystal arrangements and compositions of superparamagnetic Describe particles. The stabilization takes place by chemically covalent anchoring of suitable stabilizers on the particle surfaces, with several different ones Stabilizers and statistical, biologically functionalized stabilizers are used can. The size spectrum of the claimed superparamagnetic particles (Diameter from 5 to 20 nm) does not correlate with the molecular weights of the proposed stabilizers, that is, at best the particles at the bottom of the size range can be effectively with the proposed stabilizers stabilize sterically. All other particle / stabilizer combinations are unstable colloidal dispersions.  

DE 37 09 852 A1 describes ferrofluids similar to those in applications EP 284 549 A2, DE 37 09 851 AI and US 5,160,725 A1 are described, but with technical Applications as a target group. The proposed or described steric Stabilizers are in no way capable of containing superparamagnetic particles Diameters <10 nm, which are also included in the claim of the application, effectively to stabilize sterically. There are no indications as to how defined and composed crystallized superparamagnetic materials can be produced and that the Use of such materials in ferrofluids is desirable.

DE 43 09 333 A1 and DE 44 07 338 A1 describe superparamagnetic units Particles based on iron, iron oxide and mixed iron oxide, the individual superparamag netic particles have diameters between 5 and 20 nm and the aggregates between 10 and 1000 nm are large. It is claimed that such particles could be steric Stabilizers for various technical, biological and medical applications are functionalized and have molecular weights of <approx. 20,000, effectively sterically stable be lized. However, the latter is impossible according to the basics of colloid chemistry. The functionalized stabilizer molecules described are Polyalkylene copolymers that functionalize via statistical polymer-analogous reactions will. The proportion of superparamagnetic material in the Aggregates would be between 90 and 98%. However, no method is described which could produce such levels of magnetic material. On the importance of Crystallization process for the formation of optimal superparamagnetic particles is included not received a word.

Mair and Steck (US 4,810,401) describe new manganese-zinc ferrites and the like in their patent. a. Mixed oxides used in the production of superparamagnetic liquids with high Saturation magnetizations (60 nTm3 / g) can be used. According to the Particles of the aforementioned ferrites with a diameter of 5 to 15 nm are recorded possess, by means of low molecular weight, anionic surfactants in different Dispersed dispersion media that have a boiling point of at least 100 ° C. This is However, according to the theory of colloid chemistry, this is actually impossible. The applied Dispersion processes also appear to be constructed in the context and are probably only the purpose is to avoid conflicts with applications / patents of other applicants. With Look at the crystallization processes that occur during the manufacture of the colloidal ferrite particles must take place, there are only hints for those that occur during normal  Metal salt falls occur. It can be deduced that as a result of much too drastic precipitation conditions only crystal orders of very limited quality are generated.

Kormann et al (DE 43 27 223 A1, DE 41 15 608 A1, DE 43 27 225 A1, EP 580 878 A1, DE 42 13 513 A1 and DE 44 30 285 A1) describe various super in their applications paramagnetic and ferromagnetic colloidal particles, which i.a. according to the known Precipitation processes are generated in an alkaline medium, and their aqueous dispersions. In none of the applications will indicate the need for a defined crystal growth processes for optimal superparamagnetic or ferromagnetic particles given. The aqueous dispersions are produced by means of polyelectrolytes or Copolymers with high numbers of monomers with anionic groups achieved under different molecular weights up to M.W. = 250000. Related to physio logically compatible colloidal dispersions are incorrectly claimed to be such Stabilized colloids (stabilizer molecular weights in these cases ≦ 25000) are in physiological environment stable. However, the latter is impossible because of the effective combination nated steric stabilization mechanism of the polyelectrolytes in strong environment containing electrolytes is ineffective. The manufacture of all of the aforementioned colloidal Dispersions always occur through the mechanical mixing of the colloidal magnetic Particles with the stabilizer substances in the ultrasonic field.

Günther (DE 195 16 323) describes superparamagnetic in principle in his application Iron oxide particles that have the "usual" poor quality in terms of crystal construction. He also describes bifunctional stabilizer molecules for the production of ferro fluids in an aqueous environment. Functionality becomes chemical or physical Anchoring the stabilizer on the metal oxide particles used. The second functionality stands for "surface modification of the finished ferrofluids in the sense of specific technical and medical questions ". On the one hand, this means that the Günther significantly stressed fluids with those of Kresse et al. to match. On the other hand, it is clear that the "functionalization" of the claimed stabilizer is still is not useful in the application technology sense, since the latter only through the aforementioned Surface modifications can be achieved.  

The state of the art can thus be summarized as follows:

• 1) Colloidal superparamagnetic and ferromagnetic particles often contain Fe ₃ O ₄ , γ- Fe ₂ O ₃ , mixed oxides of these two substances, other mixed oxides based on iron and metallic particles of ferromagnetic elements.
• 2) In the production of such superparamagnetic or ferromagnetic particles did not pay attention that the resulting particles have a particularly favorable (desired) Content of superparamagnetic or ferromagnetic material and a special one possess favorable (desired) crystal structure (with a defined number of crystal defects).
• 3) As far as stable colloidal dispersions of superparamagnetic or ferromagnetic Particles are described which are sterically stabilized and in which the steric Stabilizer layers contain biofunctional molecules (target molecules), so the Biofunctionalization either
• a) by directly anchoring the functionalizing molecules on the particles themselves,
• b) on precursors of the stabilizers via statistical polymer-analogous reactions,
• c) via statistical copolymerization and
• d) via (Kresse patent; Günther) by physical adsorption of the target molecules or Molecules containing the target molecules on the layers of the (actual) steric Stabilizer.
• 4) In the field of water soluble colloidal dispersions, the superparamagnetic or Ferromagnetic particles are included in a variety of the present patents and applications contain information on the general laws of chemistry (in particular contradict colloid chemistry).
• 5) The production of colloidal dispersions of superparamagnetic or ferromagnetic Particles take place either according to the one-pot method or the two-pot method. At the former finds the generation of superparamagnetic or ferromagnetic particles in The presence of the steric stabilizer molecules takes place, while in the latter the steric Stabilization after the generation of superparamagnetic or ferromagnetic particles is carried out. As a result of one or the other "tailoring" of the colloids produced for special applications, especially in the medical sector, the Number of work steps to be carried out in general significantly over "one" or "two", ent speaking of the naming of the different manufacturing processes.

5. The invention

It is the object of the present invention to overcome the disadvantages of the prior art eliminate and new dispersible particles, especially colloidal, processes for their Manufacturing and delivering these new particles.

Very special dispersible particles are superparamagnetic and / or ferromag netische, with regard to their crystal structure and the content of superparamagnetic and / or ferromagnetic material are optimized for the respective application. This have defined levels of superparamagnetic and / or ferromagnetic material between 0.001 and 99.999 vol .-%, in particular 30 to 90 vol .-%, and crystal structures with a share of crystal defects in the superparamagnetic or ferromagnetic phase between 0.001 and 99.999% by volume, in particular 1-10% by volume.

In addition, methods for producing such defined particles are superparamagne tables and / or ferromagnetic material presented.

Another important aspect of the solution to the problem relates to special, tailor-made di-, tri- and multi-block copolymers which are part of the novel dispersible particles and which, as steric stabilizers in technical, biological and medical applications, are more stable or unstable, in particular dispersions colloidal, especially such superparamagnetic and / or ferromagnetic safe particles, can act in polar or non-polar dispersion media, are optimized for the respective application and have the following structure:

• (I) A first or more poly (oligo) mer and / or copoly (oligo) mer graft, side or Main chain blocks that are physically adsorptive or chemically covalent or otherwise dispersible particles, especially colloidal, especially superparamag netic and / or ferromagnetic material, can interact and thereby a stable anchoring of the block copolymer with the aforementioned particles in the In terms of the steric stabilization mechanism of colloidal dispersions,
• (II) a second or more poly (oligo) mere and / or copoly (oligo) mere linear or branched main chain blocks which - in the case of stable dispersions, in particular colloidal ones, especially such superparamagnetic and / or ferromagnetic material - for those  steric stabilization in the respective dispersion medium are responsible and (optional)
• (III) a third or more poly (oligo) mer or copoly (oligo) mer graft, side or Main chain blocks in which physically and / or chemically and / or otherwise reactive Groups are included, which are used throughout the use of the particles, especially colloidal ones especially of superparamagnetic and / or ferromagnetic particles, or their disper sions in polar or non-polar dispersion media in technical, biological, medicine ical or veterinary area with substances or bodies or body parts can react, either deliberately inserted into the dispersion media or with which the particles or their dispersions come into contact with.

In particular, di, tri and more block copolymers are provided which are part of the novel dispersible particles and which, as steric stabilizers in biological and medical applications, are stable or unstable, aqueous, dispersions, in particular colloidal, very particularly those superparamagnetic and / or ferromagnetic particles, can be used, are optimized for the respective application and have the following structure:

• (I) A first or more poly (oligo) mer and / or copoly (oligo) mer graft, side or Main chain blocks that are physically adsorptive or chemically covalent or otherwise Particles, especially colloidal, very specifically such superparamagnetic and / or ferromagnetic material, can interact and thereby a stable Anchoring the block copolymer with the aforementioned particles in the sense of steric Mechanism of stabilization of colloidal dispersions,
• (II) a second or more poly (oligo) merer and / or copoly (oligo) mer, linear or branched main chain blocks which - in the case of stable dispersions, in particular colloidal ones, especially such superparamagnetic and / or ferromagnetic particles - for those steric stabilization in the respective dispersion medium are responsible and (optional)
• (III) a third or more poly (oligo) mer or copoly (oligo) mer graft, side or Main chain blocks in which physically and / or chemically and / or otherwise reactive Groups are included, which are quite during the use of the particles, especially colloidal ones especially of superparamagnetic and / or ferromagnetic particles, or their disper ions in aqueous dispersion media in biological, medical or veterinary media can react with substances or bodies or parts of the body that  either deliberately inserted into the dispersion media or with which the particles or their dispersions come into contact.

The solution to the problem also includes the provision of procedures for Production of the above-mentioned special, tailor-made di, tri and more block Copolymers.

The result is another partial aspect of the solution to the task of the present one Invention Applications of the above-defined superparamagnetic and / or ferromagnetic particles in technical, biological, medical and veterinary field.

Finally, another aspect of the solution to the problem concerns applications of stable and unstable dispersions of dispersible particles in technical, biological, medical and veterinary field that only the aforementioned, contain custom di, tri and more block copolymers.

In summary, and in accordance with the main claim and its further developments, the present invention thus provides dispersible particles which in particular also contain tailored di-, tri- and more-block copolymers, as are shown schematically in FIGS. Ac.
Fig. A ₁
Fig.a ₂
Fig.a ₃
Fig.b ₁
Fig.b ₂
Fig. C.

6. Detailed description

Superparamagnetic and ferromagnetic materials in the sense of the present invention are all crystalline arrangements of atoms, molecules or groups of molecules, the individual atoms, molecules or groups of molecules carrying at least one non-compensated elementary magnetic moment and permanent interrelation due to interatomic or intermolecular interaction in the crystal structure of the elementary magnetic moments can take place. In such ferromagnetic materials there is a permanent, mutual alignment of the elementary magnetic moments. In such superparamagnetic materials there is a permanent, mutual alignment only when external magnetic fields with (arbitrarily) small magnetic induction act, since in the absence of external magnetic fields the thermal energy of the elementary magnetic moments prevents a permanent, mutual alignment. In particular, superparamagnetic and ferromagnetic materials in the sense of the present invention are particles of: Fe ₃ O ₄ , γ-Fe ₂ O ₃ , mixed crystals of Fe ₃ O ₄ and γ-Fe ₂ O ₃ , manganese-iron-ferrite, cobalt-iron- Ferrite, nickel-iron ferrite, zinc-iron ferrite, hexagonal ferrites, e.g. B. those of the composition BaFe _12-xy M _x ^II M _y ^IV O ₁₉ or SrFe _12-xy M _x ^II M _y ^IV O ₁₉ , with x = 0-1, y = 0-1 and M ^II = Mn, Fe , Co, Ni, Zn, Cu, Mg, Cd and M ^IV = Ti, Zr, Sn, Nb, Berthollide, cubic ferrites of the composition M _a Mn _b Zn _c Fe _d O _e , with a, b, c = 0, 00-0.99, d = 2.00-2.99, e = 3.01-4, a + b + c = 0.01-0.99 and a + b + c + d = 2.00- 3.00 and iron, cobalt, nickel, gadolinium and their mixed crystals. Very particularly preferred superparamagnetic and ferromagnetic materials for the purposes of the present invention are Fe ₃ O ₄ , γ-Fe ₂ O ₃ , mixed crystals of Fe ₃ O ₄ and γ-Fe ₂ O ₃ , and iron, cobalt, nickel, gadolinium and their mixed crystals .

Crystal defects in the sense of the present invention are all interference in the coupling elementary magnetic dipoles of ferromagnetic substances by the presence of foreign atoms, molecules or molecular assemblies in the crystal poisoner in which the respective Substances show ferromagnetic (solid state) behavior. In addition, such Disturbances can be caused by distortions of the crystal lattice, which result from improper appropriate crystallization occur. Typical crystal defects in crystalline (inorganic) Fabrics are e.g. B. in R. Zimmermann, K. Günther, Metallurgy and Materials Technology, VEB Deutscher Verlag für Grundstoffindustrie, 1975, p. 161 described. Generally can Crystal build errors increase the macroscopic magnetic moment of the crystals or  lower, since antiparallel arrangements of elementary magnetic dipoles either arise or be canceled. The term "disorder" in the sense of the previous one Definition therefore refers to the deviation of the macroscopic magnetic Mo mentes of that which in the prior art of ferromagnetic materials than that (theoretically) the largest possible for the specific, crystal-error-free Material composition is known. The extent of the crystal defects is called the quotient "Undisturbed crystalline particle volume / total particle volume" expressed and can be compared with the present saturation magnetization (theoretical) determine that in the prior art as the highest possible for each Material composition is known.

Crystal defects in the sense of the present invention are only those in the superpara magnetic or ferromagnetic phase of each particle present. The Composition and structure of other phases in the respective particles any and i.a. adjusted so that the entirety of the dispersible particle is optimal Functionality guaranteed in the sense of the respective application.

The superparamagnetic and / or ferromagnetic particles of the present invention are by special embodiments of methods known per se for production dispersible particles produced. These are the mechanical processes for shredding Larger ferromagnetic particles and various nucleation processes in which the superparamagnetic and / or ferromagnetic particles made of atomic or molecular Species are generated. The quality of the crystal orders becomes different Times. In the case of mechanical crushing processes, the crystalline one Structure already defined in the material to be shredded before the grinding process, in the course of the Shredding is only slightly changed, since the materials treated in this way generally very are brittle, therefore more likely to break than plastic (via the generation of lattice defects) To experience deformations. The situation is different with the nucleation processes. Here will the crystal structure essentially during the synthesis of the particles by atomic and / or molecular growth processes set. Often it is the resultant Crystal orders but not yet those of superparamagnetic or ferromagnetic Substance, rather that of its precursors. In such cases, the quality of the Crystal order of the superparamagnetic and / or ferromagnetic particles then also  through the conversion process "precursor → superparamagnetic / ferromagnetic Material "influenced.

The emergence and growth of the crystals of superparamagnetic and / or ferro magnetic substances, or the production of the dispersible particles of the same material in the For the purposes of the present invention, it is principally done according to the well-known thermodynamics Amish laws (see e.g. R. Zimmermann, K. Günther, Metallurgy and Plant stofftechnik, VEB German publishing house for basic material industry, 1975, p. 161). From these zu coherence shows that the crystal quality, i. H. especially the amount of grid construction errors, very much depends on the respective experimental conditions. A general regulation for the generation of defined crystal structures with different Boundary conditions cannot be given or only to the extent that these can be met with the abstract physical-chemical quantities of the thermodynamics of crystallization, which are difficult to transfer to specific, empirical crystal growths. Optimal empirical crystallization conditions for the production of defined structures superparamagnetic and / or ferromagnetic materials are consequently generally With Process parameters described, under which the desired material qualities reproducibly manufactured.

The growth / crystallization of the superparamagnetic and / or ferromagnetic mate rialien, d. H. the formation of dispersible particles in the sense of the present invention, ge looks under system-specific optimized process parameters that vary from material to material Differentiate material and take place under conditions in which - system-specific - fixed and / or liquid and / or gaseous material flows, the neutral-atomic, neutral-molecular, ionic-atomic, ionic-molecular, radical-atomic, radical-molecular, radicalionic atomic, radicalionic-molecular, radioactive-atomic, radioactive-molecular character and can have combined character of the aforementioned types, brought together in this way be that the desired, defined levels of superparamagnetic and / or ferro magnetic material between 0.001-99.999 vol .-%, preferably 30-98 vol .-%, and the Desired defined crystal structures with proportions of crystal defects in the area between 0.001-99.999 vol .-%, preferably 0.001-10 vol .-%, reproducibly generated will.  

A particular embodiment of the growth / crystallization of superparamagnetic and / or ferromagnetic materials, ie the formation of dispersible particles in the sense of the present invention, in the sense of the present invention is a nucleation process with which superparamagnetic and / or ferromagnetic metal, metal oxide and mixed metal oxide -Particles with a defined content of metal, metal oxide or mixed metal oxide between 0.001-99.999 vol .-%, preferably 30-98 vol .-%, and defined crystal structure, which has a proportion of crystal defects between 0.001 and 99.999 vol .-%, preferably 0.001- 10 vol .-%, can be produced. The process includes

• a) polar and / or non-polar liquids,
• b) suitable salts and / or compounds of ferromagnetic elements and
• c) (optional) suitable precipitation and / or reducing agents.

In addition, other auxiliary substances can be used to improve the property spectrum serve the particles, find application.

A very special variant of the growth / crystallization of superparamagnetic and / or ferromagnetic materials, ie the formation of dispersible particles in the sense of the present invention, in the sense of the present invention is a nucleation process with which superparamagnetic and / or ferromagnetic metal oxide and metal mixed oxide particles with a defined content of metal oxide or mixed metal oxide between 0.001-99.999% by volume, preferably 30-98% by volume, and a defined crystal structure which contains a proportion of crystal defects between 0.001 and 99.999% by volume, preferably 0.001-10% by volume %, has, manufactured. The process includes

• a) polar and / or non-polar liquids,
• b) suitable salts of ferromagnetic elements and
• c) suitable means of precipitation.

In addition, other auxiliaries that are used to improve the Property spectrum of the particles serve, find application.

The most preferred embodiment of the growth / crystallization of superparamagnetic and / or ferromagnetic materials, that is to say the formation of dispersible particles, in the sense of the present invention, is a nucleation process with which superparamagnetic and / or ferromagnetic iron oxide particles with a defined content of Iron oxide between 0.001-99.999 vol .-%, preferably 30-98 vol .-%, and defined crystal structure, which has a proportion of crystal defects between 0.001 and 99.999 vol .-%, preferably 0.001-10 vol .-%, can be produced . The process includes

• a) water,
• b) iron (II) and iron (III) salts and
• c) ammonia, NaOH or KOH.

The superparamagnetic and / or resulting from the aforementioned manufacturing process ferromagnetic particles have any size in the range <1 nm, preferably 1- 350 nm, with any geometry at the same time. In the case of anisotropic geometries this applies Particle size for the largest dimensional expansion. Very special particles that come from the result from the aforementioned manufacturing processes, are superparamagnetic and / or ferromagnetic and have a platelet-shaped geometry and sizes in the range <1 nm, preferably 1-350 nm. The two-dimensional geometry of the platelets is "rectangular ↔ elliptical ".

A partial aspect of the present invention provides special, tailored di, tri and more block copolymers used for the steric stabilization of dispersible particles, in particular colloidal, especially superparamagnetic and / or ferromagnetic particles, in Dispersions in polar or non-polar media can serve. Such dispersions can be stable or unstable. Those which can be coated with such steric stabilizers Particles generally include all types of dispersible particles, in particular colloidal, and especially such superparamagnetic and / or ferromagnetic Materials. Very special superparamagnetic and / or ferromagnetic particles with stabilizers of this type can be coated in a defined manner superparamagnetic and / or ferromagnetic particles with sizes <1 nm, preferably 1- 350 nm, and any geometry. Colloidal particles of this type have a defined structure a defined proportion of ferromagnetic material between 0.001 and 99.999 vol .-%, preferably 30-98 vol .-%, with a simultaneously defined crystal structure in the superparamagnetic and / or ferromagnetic phase, with a share of crystal structure errors of 0.001-99.999% by volume, preferably 0.001-10% by volume.

The specific, tailor-made di, tri and more block copolymers generally have a Graft main chain and / or side chain main chain and / or a simple main chain structure in which one or more graft and / or side chains and / or main chain blocks  for anchoring the di, tri or more block copolymers to the respective, too stabilizing particles are used. This anchoring can be achieved with a chemically covalent, physically adsorbent or other type of binding. In particular, it is done via physically adsorbent bonds.

The term "graft backbone structure" is related to the anchor block and defined in the sense of the present invention so that the arrangement of the anchoring used graft chain blocks in the di, tri or more block copolymers so pronounced is that the respective parts of the sterically stabilizing main chain middle block still can bring about steric stabilization when it comes to stable sterically stabilized To produce dispersions. In addition, the order cannot target the intended Effect by optional targeting blocks in the di, tri or more block copoly are present, is caused, impair. In contrast, are unstable in the case of coated dispersions limited the arrangement options only to the extent that the intended targeting effect is not adversely affected.

The term "side chain main chain structure" is related to the Anchoring block and defined in the sense of the present invention so that the arrangement of the side chain block used for anchoring in the di, tri or more Block copolymers is so pronounced that the respective parts of the sterically stabilizing acting main chain middle blocks can still cause steric stabilization if it this is about producing stable, sterically stabilized dispersions. In addition, the Arrangement does not have the intended targeting effect provided by optional Targeting blocks present in the di, tri or more block copolymers will affect. In contrast, in the case of unstably coated dispersions Arrangement options only limited to the extent that the intended targeting effect is not adversely affected.

Should a main chain block for anchoring the customized di, tri or more Block copolymers are responsible for the respective dispersible particles, so is his Arrangement in the di, tri or more block copolymer such that (I) - in the case of stable sterically stabilized dispersions - the sterically stabilizing effect of sterically stabilizing main chain blocks (or the blocks) and an intended targeting Effect that is provided by optional targeting blocks that are in the di, tri or more  Block copolymers are present, is caused, not impaired and (II) - im In the case of unstably coated dispersions - an intended targeting effect is not is adversely affected.

The structures of the anchoring blocks in the tailor-made di, tri or more block copolymers is so pronounced that it is either linear or (several) ver branches and / or grafted blocks may be present. restrictions With regard to possible structures, it only follows from the rule that the mode of operation is Anchoring on the respective particles must not be significantly impaired.

The structure of the (optionally) sterically stabilizing main chain block in the tailored The third di, tri or more block copolymers is so distinctive that it is either linear or there may also be (several) branches and / or grafted blocks.

The individual blocks available in the tailored di, tri or more block copolymers can be a polymer and / or copolymer and / or oligomer and / or cooligomer Possess character and either in the polar or non-polar liquid media in which the resulting particles should be dispersed stably or unstably, be soluble or insoluble. In the case of stable dispersions, there is the restriction that at least one of them Single block, which is present in the skin chain part of the di, tri or more block copolymers, in the polar or non-polar liquid medium must be readily soluble in such a way that a stable dispersion of the particles is created.

The structural structure of the complex "(superparamagnetic and / or ferromagnetic and / or other) particles / tailor-made di, tri and / or more block copolymer " is generally so pronounced that it is anchored by an "independent" block, the che mixed covalently, physically adsorbent or otherwise with the dispersible particles interacts. Steric stabilization is possible using a (linear) medium permanent block for which the intended dispersion medium is such a solvent, that its hydrodynamic expansion is sufficient for a steric stabilization process is. The "stabilization block" is followed by a cover block, which is the linear mean permanent block and in which specific atoms, molecules and. a. are present that a Targeting the complex in terms of the specific application in technical, biological, medical or veterinary field.  

However, it is for those who are familiar with the prior art of colloid chemistry and poly merchemie, obviously, that the aforementioned structural structure of the complexes "(superparamagnetic and / or ferromagnetic and / or other) particles / tailor-made di-, tri- and / or more block copolymer "can vary in many ways only due to different structures of the di, tri or more block copolymers used.

Customized di-, tri- and more-block copolymers are therefore very general in the sense of present invention all those which have graft, side and main chain structures and such with dispersible particles of any material, especially colloidal, whole especially superparamagnetic and / or ferromagnetic material can be combined can form stable or unstable dispersions of the resulting complexes and they can be used in the sense of the respective intended (targeting) application.

The blocks of the targeting component that are optional in the di, tri, or more block copoly are present, are generally as components of the (linear) main chain of the di-, tri- or more block copolymers available (see above). But they can also be used as graft or sides chains are present, as long as (I) has a sterically stabilizing effect of the head chain blocks is not affected and / or (II) the coupling to the dispersible Particles, especially colloidal, very specifically from superparamagnetic and / or ferro magnetic particles, by means of which the anchoring blocks are not impaired and / or (III) the targeting effect, which is based essentially on the fact that the targeting blocks in the outer shell of the complexes "(superparamagnetic and / or ferromagnetic and / or different type) particle / tailor-made di-, tri- and / or more block copolymer "available are not affected.

In special cases, the (optionally) sterically stabilizing main chain block can also at the same time for targeting the dispersible particles in stable or unstable Dispersions may be responsible.

The structures of the targeting blocks in the tailored di, tri or more block co polymer is so pronounced that it is either linear or (several) branches gung and / or grafted blocks may be present. Limitations on possible structures result only from the rule that the functionality for targeting in the sense of the intended application of the resulting particles or their stable ones  or unstable dispersions in polar or non-polar media are not significantly impaired may be.

The task of targeting blocks in the tailored di, tri and more block copoly meren it is generally unstable or stable sterically stabilized (coated) complexes of the type "(superparamagnetic and / or ferromagnetic and / or other) particles / tailor-made di, tri and / or more block copolymer "with specific molecules that either deliberately inserted into the dispersion media or with which the superpara magnetic and / or ferromagnetic and / or other types of particle complexes or their Dispersions come into contact, in physically adsorbent, chemically covalent or the like. To bring interaction. Thus, the targeting blocks do not necessarily contain Active substances that are released after targeting at the respective place of use (e.g. split off). For the purposes of the present invention, therefore, can be tailored di-, tri- and more block copolymers, which probably contain one or more targeting blocks, the latter, however, do not contain any active ingredients that are released after targeting (e.g. can be split off, optionally also blocks or the like in the molecular framework. included in which such active substances are chemically covalent, physically adsorbent or otherwise are bound. The nature of the cooperation is limited only by the fact that it does not (I) the anchoring of the tailor-made di-, tri- or more-block copolymers on each only dispersible particles and / or (II) an intended steric stabilization of the produced complexes "(superparamagnetic and / or ferromagnetic and / or otherwise like) particles / tailor-made di-, tri- and / or more block copolymer "not disadvantageous is influenced and / or (III) the targeting effect of the corresponding blocks of the measure Tailored, di, tri and more block copolymers themselves are not adversely affected.

The tailor-made di, tri or more block copolymers are produced by means of of special combinations of the variety of chemical reactions of the general inorganic and organic chemistry, biochemistry, polymer chemistry u. a. more specific Areas. These reactions are well described in textbooks and monographs from respective areas (e.g. H. Becker et al. ORGAMKUM, VEB German Publishing House of Knowledge Berlin, 1969 and G. Jander and E. Blasius, introduction to inorganic-chemical Internship, S. Hirzel Verlag, Stuttgart 1980) and therefore do not have to be special at this point are described, in particular also for the reason that, depending on the specific case vary widely.  

In connection with the present invention, the term "manufacture" does not include only the implementation of the various polymer-forming u. a. polymer-modifying Reactions. Rather, it also includes the variety of different types of reactions that lead to Representation of monomers, oligomers and. a. Molecules that are used for polymerization themselves or are required for other reaction steps.

Examples of di, tri and more block copolymers, including their production in the sense of The present invention for the technical field are e.g. B. in the parallel German Patent application 196 31 563 described. Examples of di, tri and more block copolymers and their manufacture for use in the medical field are in the present Er described. Application examples for further di, tri and more block copolymers in medical field are e.g. B. in the patent applications WO 96/04017 A1, DE 43 09 333 A1 and DE 44 07 338 A1. There are also a variety of substances listed that are chemically covalent with each other in the sense of the present invention connect with the end result of further, new, tailor-made di-, tri- and more block copolymers for use in the medical field.

Another embodiment of the present invention provides the use of the novel dispersible particles in stable or unstable dispersions that are defined built up particles of superparamagnetic and / or ferromagnetic material in the sense of present invention and / or special, tailored di, tri and / or more Block copolymers in the sense of the present invention contain.

Stable or unstable dispersions of dispersible particles in the sense of the present invention thus contain at least either the defined superparamag particles netic and / or ferromagnetic material in the sense of the present invention or the special, tailor-made di-, tri- and / or more block copolymers in the sense of present invention.

Unstable dispersions of dispersible particles for the purposes of the present invention those that have defined superparamagnetic and / or ferromagnetic particles Contain materials in the sense of the present invention and which no coating with steric stabilizers, which are used either in the manufacture of ferrofluids for technical, biological and medical field are common or which are such  tailor-made di-, tri- and / or more block copolymers in the sense of the present Invention acts own. Optionally, such unstable dispersions can also electrostatic double layers on the individual particles of the defined structure superparamagnetic and / or ferromagnetic material. The fat Such electrostatic bilayers is, however, due to the special conditions where the instability of the dispersions is no longer sufficient by one To ensure electrostatic stabilization of the present, uncoated particles. Other unstable dispersions of dispersible particles for the purposes of the present invention are those in which particles, especially colloidal ones, and especially those superparamagnetic and / or ferromagnetic material, with tailor-made di-, tri- and / or more block copolymers coated for the purposes of the present invention are that no effective steric stabilization can occur. The causes of such ineffective steric stabilization processes are known in the art Colloid chemistry described (see prior art). Very special unstable dispersions For the purposes of the present invention, dispersible particles are those in which dispersible particles of superparamagnetic and / or ferromagnetic material a defined content of superparamagnetic and / or ferromagnetic material and contain a defined crystal structure, both in the sense of the present invention, and such as with steric stabilizers that are used in the production of ferrofluids for technical, biological and medical fields are common or with such customized di-, tri- and / or more block copolymers for the purposes of the present invention are coated, that no effective steric stabilization can occur.

In any case, the term “dispersion” means that the present ones are uncoated or coated particles into a liquid, polar or non-polar, especially aqueous, Dispersion medium are introduced and dispersed, d. H. possibly existing aggregates Several particles are destroyed or the size of the aggregates is in the tolerable range the respective application. Following this dispersion process, the instability becomes apparent of the respective dispersions then that they are completely or partially within a Period of up to 6 months after dispersion at room temperature, i.e. H. 20-25 ° C, fail under gravitational conditions.

Stable dispersions of dispersible particles for the purposes of the present invention in principle those as dispersible above in connection with unstable dispersions  Particles have been described, but in this case with the premise that either the electrostatic stabilization mechanism or the steric stabilization mechanism or a combination of both stabilization mechanisms is effective, d. H. the failure of the respective particles or their aggregates over a period of 6 months at 20-25 ° C prevented under gravitational conditions.

Non-polar liquid dispersion media in the sense of the present invention are those whose dielectric constant is less than 22. Such non-polar liquids can be made from a single liquid or a mixture of several non-polar and / or polar Be liquids. Furthermore, non-polar liquid media in the sense of the present Invention also contain dissolved or dispersed substances, but their non-polar character should not be changed. Such dissolved or dispersed substances can also in The shape of micelles is present in the respective dispersion medium. As far as dispersed substances in the nonpolar dispersion media in the sense of the present invention are present these are alien to the particles to be actually dispersed in the sense of the present Invention. Special non-polar dispersion media in the sense of the present invention are Emulsions from immiscible, non-polar and / or polar liquids, which are also optional Contain surface-active substances and / or dispersed substances and / or dissolved substances can.

Polar liquid dispersion media in the sense of the present invention are those as in Have been described in connection with the non-polar liquid dispersion media, however with a dielectric constant ≧ 22.

The definition of the term "micelles" is in the prior art of surface-active substances Colloid chemistry defined.

Aqueous dispersion media in the sense of the present invention are generally those that come from consist of pure water. Optionally, electrolytes and / or polymers can also be used in the water o.a. Substances can be dissolved and / or dispersed, also micelle-like.

An 08128 00070 552 001000280000000200012000285910801700040 0002019654965 00004 08009 other types of aqueous dispersion media are those which at least consist of 50% by volume, preferably 80-90 vol .-%, water exist. The rest consists of polar, with water miscible organic solvents, the permissibility of organic  Solvents as part of the dispersion medium of the particular one Application is dependent. On the other hand, organic solvents may also be desirable properties resulting from the resulting dispersions, e.g. B. rheological. Optionally, electrolytes and / or polymers or the like can also be used in these dispersion media. Substances can be dissolved and / or dispersed, also micelle-like.

Another type of aqueous dispersing agent form emulsion-like dispersing agents, in which the aqueous phase makes up at least 50% by volume, preferably 80-90% by volume. The Zusäs liquid of emulsion-like dispersion media as dispersion media for the respective dis pergeable particles in the sense of the present invention is of the respective application dependent. Possible compositions are suitable emulsion-like dispersion media e.g. B. All those included in the prior art of emulsions and suspensions. Optionally, electrolytes and / or polymers or the like can also be used in these dispersion media. Substances can be dissolved and / or dispersed, also micelle-like.

But it is also a partial aspect of the present invention dispersible particles that are superparamagnetic and / or structured ferromagnetic material in the sense of the present invention and / or customized contain di, - tri- or more block copolymers for the purposes of the present invention.

I.a. can the above-described particles of superparamag netic and / or ferromagnetic material and the tailor-made di, - tri or multi-block copolymers in stable or unstable dispersions containing these particles or which contain tailored di, tri or more block copolymers, or both Types of substance included, used in any technical, biological or medical application in which the existing material properties of the particles, the tailor-made di, tri- or more block copolymers and / or the stable or unstable dispersions be used to advantage.

Very special applications of defined particles made of superparamagnetic and / or ferromagnetic material in the technical field are in the (from divorced) parallel German patent application on finely divided, dispersible Material combinations containing electronically intrinsically conductive polymer are described.  

Very special applications of stable and unstable dispersions, which either The aforementioned defined colloidal particles or customized di, - tri or more block copolymers in the sense of the present invention or both components contained in the medical field can be found in NMR diagnostics and others Applications in which the significance of diagnostic examinations is important increase and / or medicinal agents by means of stable or unstable dispersions targeted to transport to the diseased body area (part). Examples of such Applications are in large numbers, for. B. in the patent applications WO 96/04017 A1, DE 43 09 333 A1 and DE 44 07 338 A1.  

6. Examples example 1 Production of ferromagnetic reacting (superparamagnetic) particles with a defined structure

2 mol of iron (III) chloride, hexahydrate and 1 mol of iron (II) chloride, tetrahydrate were in 5 l distilled water. Then the pH of the resulting solution was checked Drops of NaOH set between 10 and 11, using a Mechanical agitator was homogenized and the reaction at room temperature took place. The rate of addition of the base was varied. The total amount of base was added within 2.5 h. After completion of the particle synthesis, the Iron oxide suspension stirred for a further 2 h. Finally the pH of the suspension reduced to a neutral value by decanting and diluting with distilled Water happened. The generated iron oxide particles consist of 60 vol.% Ferromagnetic reacting material, whereby a crystal construction error content of 30% was determined.

Example 2 Preparation of a tailored tri-block copolymer containing styrene-4-sulfonate, sodium salt, 2-acrylamido-2-methyl-1-propanesulfonic acid, acrylamide and (with glucamine) amidized acrylic acid Step 1: amidization of acrylic acid with D-glucamine

2 g of D-dlucamine were dissolved in 400 ml of anhydrous DMF at 4 ° C. Then 1 g of acrylic Acid chloride dissolved in 100 ml of anhydrous DMF at 4 ° C. After combining both solutions the mixture was stirred at 4 ° C for 24 h in a dried nitrogen atmosphere. The reak tion product was precipitated with 1.5 l acetone and freeze-dried at 4 ° C.

Step 2: Synthesis of oligomeric / short-chain polymeric styrene-4-sulfonate, sodium salt / 2-acrylamido-2-methyl-1-propanesulfonic acid molecules

8.26 g of styrene-4-sulfonate, sodium salt and 16.87 g of 2-acrylamido-2-methyl-1-propane sulfone acid were dissolved in 400 ml of distilled water at room temperature. Then were 3.1 g of ammonium peroxodisulfate dissolved in distilled water and subsequently in the styrene Poured 4-sulfonate, sodium salt-2-acrylamido-2-methyl-2-propanesulfonic acid solution. The resulting reaction solution was stirred magnetically and its temperature to 60-70 ° C elevated. The polymerization was carried out for a reasonable period of time. Subsequently the reaction product was precipitated with an excess of acetone in a funnel collects and dried at ambient temperature for 4 weeks.

Step 3: graft block copolymerization of acrylamide and amidized acrylic acid / glucamine molecules onto the molecules from step 2

5 g of the oligomeric or short chain polyelectrolyte that was synthesized in step 1 and 14.71 g of acrylamide were dissolved in 400 ml of distilled water. Subsequently, with magnetic stirring, the adequate amount of ammonium cerium (IV) nitrate, dissolved in 250 ml distilled water, in the resulting solution of the polyelectrolyte / acrylic acid amide Ge mixed poured. Then the reaction temperature was raised to 60-70 ° C and thereby the Graft copolymerization started. After an appropriate period of time, 2.86 g of acrylic acid-D-glucamine, dissolved in 100 ml of distilled water, poured into the reaction solution.

At the end of the total polymerization time, the resulting tri-block graft copolymer precipitated with an excess of methanol, collected in a funnel and finally at 70 ° C in a vacuum drying cabinet for 24 h.

Example 3 Production of a stable, physiologically compatible ferrofluid that is suitable for medical use in hyperthermia and contains defined superparamagnetic particles and a tailor-made, steric tri-block stabilizer

Superparamagnetic particles produced according to Example 1 of the present invention were made with a solution of the customized tri-block copolymer, according to Example 2 of the present invention was prepared, the stabilization in liquid, aqueous phase took place. After stabilization, the resulting col loidal material in 10 centrifugation / redispersion cycles (with distilled water) of not  adsorbed tri-block copolymer freed. Finally, the redispersion took place in distilled water.

Claims (26)

1.Dispersible particles containing the following ingredients:

• (I) defined particles made of superparamagnetic and / or ferromagnetic material, with defined contents of superparamagnetic and / or ferromagnetic material and a defined crystal structure of the superparamagnetic and / or ferromagnetic phase and either
• a) electrostatic,
• b) steric or
• c) combines electrostatic / steric stabilization layers,
  a steric stabilization layer consisting of steric stabilizers:
• d) which are commercially available and / or
• e) from tailor-made di, tri and more block copolymers
  can exist
  or
• d) particles with an imperfect electrostatic or steric or combined electrostatic / steric coating, steric coatings being those that:
• f) are commercially available, and / or
• g) these are tailored di-, tri- or more block copolymers,
  or
• (II) particles of undefined structure, in particular those superparamagnetic and / or ferromagnetic materials which are coated with tailor-made di-, tri- or more-block copolymers, characterized in that
• a) that the defined superparamagnetic and / or ferromagnetic particles are those which have a defined content of superparamagnetic or ferromagnetic material between 0.001-99.999 vol .-%, preferably 30-98 vol .-%, and their crystal structure the superparamagnetic or ferromagnetic phase is defined in such a way that the proportion of crystal construction errors lies in the range between 0.001-99.999% by volume, preferably 0.001-10% by volume,
• b) that the defined particles made of superparamagnetic and / or ferromagnetic material are metal, metal oxide and metal mixed oxide particles,
• c) that the special, tailor-made di, tri and more block copolymers are those which consist of:
• (I) a first or more poly (oligo) mer and / or copoly (oligo) mer graft, side or main chain blocks which are physically adsorptive and / or chemically covalent and / or otherwise with particles, in particular colloidal, entirely especially such superparamagnetic and / or ferromagnetic material, can interact and thereby result in a stable anchoring of the block copolymer with the aforementioned particles in the sense of the steric stabilization mechanism of colloidal dispersions,
• (II) a second or more poly (oligo) mer and / or copoly (oligo) mer linear or branched main chain blocks, which - in the case of stable dispersions, especially colloidal, especially such superparamagnetic and / or ferromagnetic particles - for steric stabilization in the respective dispersion medium are responsible and (optional)
• (III) a third or more poly (oligo) mer or copoly (oligo) mer graft, side or main chain blocks, in which physically and / or chemically and / or otherwise reactive groups are contained, which are present during the use of the Particles, in particular colloidal, very particularly of superparamagnetic and / or ferromagnetic particles, or their dispersions in nonpolar or polar dispersion media in the technical, biological, medical or veterinary field can react with substances or bodies or body parts that are either deliberately inserted into the dispersion media or with which the particles or their dispersions come into contact.

2. Dispersible particles according to claim 1, characterized in that the Composition and structure of the non-superparamagnetic and / or ferromagnetic Areas of the defined superparamagnetic and / or ferromagnetic Particle is arbitrary.   3. Dispersible particles according to claim 1 and 2, characterized in that the Generation of defined structured particles from superparamagnetic and / or ferromagnetic material under system-specific optimized process parameters takes place that differ from material to material, d. H. under conditions where - system specific - solid and / or liquid and / or gaseous material flows that are neutral atomic, neutral-molecular, ionic-atomic, ionic-molecular, radical-atomic, radical-molecular, radical-ionic-atomic, radical-ionic-molecular, radioactive-atomic, have radioactive-molecular character and combined character of the aforementioned types can be brought together in such a way that defined levels of superparamagnetic and / or ferromagnetic material between 0.001-99.999 vol .-%, preferably 30-98 Vol .-%, and defined crystal structures in the superparamagnetic and / or ferromagnetic phases with proportions of crystal defects in the range between 0.001- 99,999 vol .-%, preferably 0.001-10 vol .-%, reproducible. 4. Dispersible particles according to claim 3, characterized in that the particles are generated with the aid of a nucleation process which has the following ingredients:

• a) polar and / or non-polar liquids,
• b) suitable salts and / or compounds of ferromagnetic elements and
• c) (optional) suitable precipitation and / or reducing agents and
• d) (optional) auxiliaries that are commonly used in the manufacture of dispersible particles
  be used.

5. Dispersible particles according to claim 3, characterized in that the particles are generated with the aid of a nucleation process which has the following ingredients:

• a) polar and / or non-polar liquids,
• b) suitable salts of ferromagnetic elements and
• (c) appropriate means of precipitation and
• d) (optional) auxiliaries that are commonly used in the manufacture of dispersible particles
  be used.

6. Dispersible particles according to claim 3, characterized in that particles are produced with the aid of a nucleation process which has the following ingredients:

• a) water,
• b) iron (II) and iron (III) salts and
• c) ammonia, NaOH or KOH.

7. Dispersible particles according to claim 1 to 6, characterized in that the defines superparamagnetic and / or ferromagnetic particles of any size in the range <1 nm, preferably 1-350 nm, with any geometry and in the case of anisotropic geometries, the particle size for the largest dimensional expansion applies. 8. Dispersible particles according to claim 1 to 6, characterized in that defines superparamagnetic and / or ferromagnetic particles built up a platelet have shaped geometry and sizes in the range <1 nm, preferably 1-350 nm, and the two-dimensional geometry of the platelets is "rectangular ↔ elliptical". 9. Dispersible particles according to claims 1-8, characterized in that the arrangement of one or more graft chain blocks used for anchoring in the di-, tri- or more-block copolymers is so pronounced that

• (I) the respective parts of the sterically stabilizing main chain middle blocks can still bring about the steric stabilization when it comes to producing stable sterically stabilized dispersions and, in addition, the arrangement does not have the intended targeting effect, which can be achieved by optional targeting blocks in the di-, tri- or more block copolymers are present, is caused, may be impaired or
• (II) in the case of unstably coated dispersions, the arrangement possibilities are limited only to the extent that the intended targeting effect is not adversely affected.

10. Dispersible particles according to claims 1-8, characterized in that the arrangement of one or more side chain blocks used for anchoring in the di-, tri- or more-block copolymers is so pronounced that

• (I) the respective parts of the sterically stabilizing main chain middle blocks can still bring about the steric stabilization when it comes to producing stable sterically stabilized dispersions and, moreover, due to the arrangement not the intended targeting effect, which may be caused by optional targeting blocks which are present in the di -, tri- or more block copolymers are present, is caused, may be impaired or
• (II) in the case of unstably coated dispersions, the arrangement possibilities are limited only to the extent that the intended targeting effect is not adversely affected.

11. Dispersible particles according to claims 1-8, characterized in that the arrangement of one or more main chain blocks which are responsible for anchoring the tailored di, - tri or more block copolymers on the respective particles is such that

• (I) - in the case of stable sterically stabilized dispersions - the sterically stabilizing effect of the sterically stabilizing main chain block (or the blocks) and an intended targeting effect by optional targeting blocks present in the di, tri or more block copolymers are present, is caused, not impaired and
• (II) - in the case of unstably coated dispersions - an intended targeting effect is not adversely affected.

12. Dispersible particles according to claims 1-8, characterized in that the structure Doors of the anchoring blocks in the tailored di, tri or more block copolymers are so pronounced that they are either linear or (several) branches and / or grafted blocks may be present and restrictions regarding possible Structures only result from the rule that the functionality for anchoring to the respective particles must not be significantly affected. 13. Dispersible particles according to claims 1-8, characterized in that the structure doors of the (optionally) sterically stabilizing main chain blocks in the tailor-made di-, tri or more block copolymers is so pronounced that it is either linear or (several) branches and / or grafted blocks may be present. 14. Dispersible particles according to claims 1-8 ', characterized in that the blocks of the targeting component, which are optional in the di-, tri- or more-block copolymers, are arranged so that

• (a) a sterically stabilizing effect of the main chain block is not impaired and / or
• (b) the coupling to the particles, in particular colloidal, very particularly superparamagnetic and / or ferromagnetic particles, is not impaired by means of the anchoring blocks and / or
• (c) the targeting effect, which is based essentially on the fact that the targeting blocks are present in the outer shell of the complexes "(superparamagnetic and / or ferromagnetic and / or other types of particles / tailored di, tri and / or more block copolymer" , is not affected.

15. Dispersible particles according to claims 1-8, characterized in that the structure structures of the targeting blocks in the tailored di, tri or more block copolymers are so pronounced that they are either linear or (multiple) branches and / or grafted blocks may be present and restrictions regarding possible structures only result from the rule that the functionality for targeting in the sense of the intended application of the resulting particles or their stable ones or unstable dispersions in polar or non-polar media are not significantly impaired may be. 16. Dispersible particles according to claims 1-8, characterized in that steric Stabilizing main chain blocks in the tailored block copolymers too at the same time for targeting the particles in stable or unstable dispersions can be responsible. 17. Dispersible particles according to claims 1-8, characterized in that the tailor-made di, tri and more block copolymers, which probably contain one or more targeting blocks, but the latter do not contain any active ingredients which are released after the targeting has taken place ( e.g. cleaved), can optionally also contain blocks or the like in the molecular framework, in which such active substances are chemically covalently, physically adsorbent or otherwise integrated and the type of incooperation is only limited by the fact that they

• (I) neither the anchoring of the tailored di, tri or more block copolymers on the respective particles and / or
• (II) an intended steric stabilization of the complexes produced "(superparamagnetic and / or ferromagnetic and / or other types of particles / tailor-made di-, tri- and / or more block copolymers" is not adversely affected and / or
• (III) the targeting effect of the corresponding blocks of the tailored, di-, tri- and more-block copolymers themselves must not be adversely affected.

18. Dispersible particles according to claims 1-8, characterized in that the Her Provision of tailor-made di, tri or more block copolymers using special Combinations of chemical reactions of general inorganic and organic Chemistry, biochemistry, polymer chemistry u. a. more specific areas. 19. Use of dispersible particles according to claim 1, characterized in that they stable or unstable dispersions in liquid, polar and non-polar dispersion media form. 20. Use of dispersible particles according to claim 1 and 19, characterized in that that the dispersion medium is aqueous media. 21. Use of dispersible particles according to claim 1, 19 and 20, characterized in that the preparation of the dispersions in the event that

• (I) the particles have an undefined structure and
• (II) the intended stabilization is steric and tailored di-, tri- and more-block copolymers are used for this,
  according to the methods for the production of such dispersions, as are customary for the production of dispersible particles.

22. Use of dispersible particles according to claim 1, 19 and 20, characterized characterized in that the preparation of the dispersions in the event that they are superparamagnetic and / or ferromagnetic particles with a defined superparamagnetic content and / or ferromagnetic material and defined crystal structure in the contain superparamagnetic and / or ferromagnetic phase, by means of a special Two-step process for the production of stable and unstable dispersions dispersible particles takes place, the synthesis of defined, colloidal, superparamagnetic and / or ferromagnetic particles takes place and in the subsequent second manufacturing specification the dispersion - and if desired, electrostatic, steric or electrostatic / steric stabilization of the  Defined superparamagnetic and / or ferromagnetic particles - im respective dispersion medium is reached. 23. Use of dispersible particles according to claim 1, 19 and 20, characterized characterized in that the number of work steps to be carried out for the manufacture the dispersions i.a. is below four steps and then the stable or unstable ones Dispersions are available in ready-to-use form. 24. Use of dispersible particles according to claim 1, 19 and 20 thereby characterized in that the existing properties of the defined particles superparamagnetic and / or ferromagnetic material or more stable or unstable Dispersions containing these particles and / or customized di-, tri- or more- Contain block copolymers and / or contain both types of substances, on technical, biological or medical area can be exploited economically. 25. Use of dispersible particles according to claim 1, 19 and 20 in medical Sector, characterized in that it is in the field of diagnostic examinations and / or the targeted delivery of medicinal substances to the diseased body area (part) (Drug targeting). 26. Use of dispersible particles according to claim 1, 19 and 20 in medical Sector, characterized in that it is used in the cancer treatment methodology of the Magnetic fluid cancer hyperthermia includes.