MICROSTRUCTURED COMPOUND PARTICLES

Description

[0001] The present invention relates to microstructured composite particles and their use.

[0002] Composite materials are already well-known and refer to a material made of two or more bonded materials that possess different material properties than its individual components. The material properties and the geometry of the components are important for the properties of composite materials. In particular, size effects often play a significant role. The bond is generally achieved through material interlocking, form-fit, or a combination of both.

[0003] Microstructured composite particles are also already known in themselves.

[0004] For example, European patent application EP 0 523 372 A1, referring to Japanese patent application JP62083029 A, discloses a method in which a first material (so-called mother particles) is coated on its surface with a second material consisting of smaller particles (so-called baby particles). For this purpose, a surface modification device (“ Hybridizer ") used, comprising a high-speed rotor, a stator and a spherical vessel, preferably having internal blades.

[0005] The parent particles and the baby particles are mixed, preferably finely dispersed, and introduced into the hybridizer. There, the mixture is preferably further finely dispersed and preferably repeatedly subjected to mechanical forces, in particular impact forces, compression forces, frictional forces, and shear forces, as well as the mutual interactions of the particles, in order to uniformly embed the baby particles in the parent particles. Preferred rotor speeds are in the range of 50 m / s to 100 m / s, based on the circumferential speed.

[0006] Furthermore, European patent application EP 0 523 372 A1 describes a fixation of the composite particles by thermal plasma spraying, preferably using a vacuum plasma spraying device (“ reduced pressure plasma spraying device ") is used, which preferably has a power output of at least 30 kW.

[0007] This method yields a medical-grade material comprising a substrate of high strength and biostability, and a layer formed on top of it, obtainable by plasma spraying of a substance with high bioaffinity. Preferred substances with high bioaffinity include hydroxyapatite, tricalcium phosphate, bioglasses, and other substances with similar properties.

[0008] German patent application DE 42 44 254 A1 relates to a method for producing composite particles by attaching a substance to the surface of a thermoplastic material having an average particle diameter of 100 µm to 10 mm, wherein the substance has a smaller particle diameter and better heat resistance than the thermoplastic material, and wherein the method comprises the steps: • First, heat the substance with the smaller particle diameter and better heat resistance than the thermoplastic material to a temperature not lower than the softening point of the thermoplastic material, while stirring in a device that has a stirrer and a heating device; • Add the thermoplastic material to the device; and • Attach the substance with the better heat resistance to the surface of the thermoplastic material.

[0009] The thermoplastic material (mother particles) of the composite particles can be, for example, pellets or beads made of various commercially available thermoplastic resins or plastics, such as ABS, AS, MBS, polyvinyl chloride, polyacetal, polyamide, polyethylene, polypropylene, polyethylene terephthalate, polystyrene, polycarbonate, or polyacrylates. The average particle diameter of the mother particles should preferably be in the range of 100 µm to 10 mm.

[0010] The term "baby particles" refers in particular to particles made of inorganic material, such as silicate-containing particles (e.g., glass beads, etc.), aluminum oxide particles, and zirconium oxide particles, as well as particles made of various metals, which are exceptionally heat-resistant and abrasion-resistant. The average particle diameter of the baby particles should be smaller than that of the parent particles and preferably 1 / 10 or less of the average particle diameter of the parent particles, i.e., typically in the range of 1 µm to 1 mm.

[0011] European patent application EP 0 922 488 A2 relates to solid composite particles obtained by modifying the surface of a solid particle by attaching fine particles to the surface of the particle acting as a core, and by growing a crystal or crystals of the fine particles on a combination of the core and the fine particles in order to fix the fine particles to the core particle in a peel-resistant manner.

[0012] Suitable cores include, among others, cellulose derivatives, starch derivatives, and synthetic polymers such as nylon, polyethylene, and polystyrene.

[0013] Suitable fine particles include, among others, carbonates, phosphates and hydrogen phosphates, such as calcium monohydrogen phosphate.

[0014] American patent US 6,403,219 B1 discloses solid composite particles obtained by modifying the surface of a solid core particle by attaching particles to the surface of the core particle in a non-peelable manner, wherein a crystal of a defined particle component is grown in a columnar or needle-like form on the core particle, the defined particles being glued to the surface of the core particle.

[0015] Suitable cores include, among others, cellulose derivatives, starch derivatives, and synthetic polymers such as nylon, polyethylene, and polystyrene.

[0016] Suitable fine particles include, among others, carbonates, phosphates and hydrogen phosphates, such as calcium monohydrogen phosphate.

[0017] The working example in this publication describes the production of composite particles made of nylon 12 with a mean particle diameter of 50 µm and tabular calcium monohydrogen phosphate with a mean side length of approximately 50 µm, in a ratio of 10:1. The composite particles are obtained using a surface modification device (Nara Machinery Co. NHS-0). In this process, a powder of nylon 12 and calcium monohydrogen phosphate is first treated with the surface modification device, and the resulting product is then suspended in a suspension of calcium monohydrogen phosphate to allow the crystals to grow on the surface. The procedure described in patent US 6,403,219 B1 is therefore quite labor-intensive.

[0018] Japanese patent application JP 9239020 A describes a hard tissue implant material comprising composite particles in which particles made of a bioaffinity material, such as hydroxyapatite or tricalcium phosphate, are coated with a high-hardness material, such as zirconium dioxide or aluminum oxide.

[0019] Patent application US 2003 / 0124242 A1 relates to capsules with a mineral coating and a core comprising a polyhydroxylated compound.

[0020] The mineral coating contains alkaline earth carbonates or basic carbonates, basic transition metal carbonates, alkaline earth and transition metal sulfates, alkaline earth borates, alkaline earth halides, and precipitated silica. Preferred alkaline earth metals include magnesium and calcium.

[0021] Polyhydroxylated compounds include polysaccharides such as threose, erythrose, arabinose, xylose, ribose, deoxyribose, rhamnose, fucose, glucosamine, galactosamine, N-acetylglucosamine, N-acetylgalactosamine, starch, amylopectin, amylose, araban, alginates, carrageenan, cellulose, chitosan, chondroitin sulfate, dextran, dextrin, fructosan, galactan, mannan, gum arabic, pectin, ghatti gum, galactoside, glycan, glycogen, hemicellulose, hyaluronic acid, inulin, lamarinarin, levan, mucoitin sulfate, nigeran, pentosan, polydextrose, and xylan.

[0022] The examples in this publication describe the fabrication of composite particles from guar with an average particle size of 32 µm and hydroxyapatite with an average particle size of 1.5 µm, or from starch with an average particle size of 10 µm and calcium phosphate with an average particle size of 1 µm. The composite particles are obtained using a surface modification device (Nara Machinery Co. NHS-0).

[0023] Patent US 5,011,862 describes thermoplastic hollow spheres, for example made of PVC, PAN, polyalkylmethacrylate, PS, which include opacifying agents attached to or incorporated into their surface, such as TiO2, ZnO, CaCO3, talc, clay materials, etc.

[0024] Patent US 4,915,884 discloses a granulate which is obtained by homogeneously mixing a thermoplastic resin, such as PE, and an additive, such as calcium carbonate, subsequently extruding this mixture and comminuting the resulting extruded strand.

[0025] European patent application EP 2163 569 A1 relates to a process for producing resin particles from an acid-containing thermoplastic resin or elastomer and a filler, such as calcium carbonate. The process generates resin particles by melting and mixing an acid-containing thermoplastic resin or elastomer with filler particles and a water-soluble material to provide a resin composition with fine resin particles formed by the thermoplastic resin and the filler particles. The resin composition is dispersed in a matrix comprising the water-soluble material. Subsequently, the matrix component is removed from the resin composition to yield the resin particles.The resulting resin particles each comprise a core particle containing the acidic group-containing thermoplastic resin or elastomer, and filler particles immobilized on the outside of the core particle. The specific, highly complex procedure described in this publication leads to a porous structure of the resin particles.

[0026] The publications by Y. Shi, Y. Sun, "Fabrication and Characterization of a Novel Biporous Spherical Adsorbent for Protein Chromatography" (Chromatographia 2003, 57, pp. 29-35) and L. Wu, S. Bai, and Y. Sun, "Development of Rigid Bidisperse Porous Microspheres for High-Speed ​​Protein Chromatography" (Biotechnol. Prog. 2003, 19, pp. 1300-1306), describe the production of polymer beads by suspension polymerization of polyglycidyl methacrylate copolymers in the presence of superfine calcium carbonate. After polymerization, the calcium carbonate is washed out to obtain polymer beads with porous structures.

[0027] However, none of the aforementioned publications considers the use of precipitated calcium carbonate particles (PCC) or resorbable polyesters as components of the described composite particles.

[0028] Furthermore, the use of precipitated calcium carbonate in connection with compounds is already known in the literature, but again not as a component of composite particles.

[0029] The publication by TD Lam, TV Hoang, DT Quang, JS Kim, "Effect of nanosized and surface-modified precipitated calcium carbonate on properties of CaCO3 / polypropylene nanocomposites," Materials Science and Engineering A 501 (2009) 87-93, describes the effect of surface-modified calcium carbonate nanoparticles on the properties of CaCO3 / polypropylene nanocomposites. In this study, the calcium carbonate particles are homogeneously dispersed as a filler within the polymer.

[0030] The publication by L. Jiang, YC Lam, KC Tam, DT Li, J. Zhang, "The influence of fatty acid coating on the rheological and mechanical properties of thermoplastic polyurethane (TPU) / nano-sized precipitated calcium carbonate (NPCC) composites," Polymer Bulletin 57, 575-586 (2006), deals with the influence of fatty acid coatings on the rheological and mechanical properties of composites comprising thermoplastic polyurethane and precipitated calcium carbonate nanoparticles. Here, too, the calcium carbonate particles are homogeneously dispersed as a filler within the polymer.

[0031] The paper by J. Cayer-Barrioz, L. Ferry, D. Frihi, K. Cavalier, R. Séguéla, G. Vigier, "Microstructure and Mechanical Behavior of Polyamide 66-Precipitated Calcium Carbonate Composites: Influence of the Particle Surface Treatment," Journal of Applied Polymer Science, Vol. 100, 989-999 (2006), examines the microstructure and mechanical behavior of composites comprising polyamide 66 and precipitated calcium carbonate nanoparticles. The calcium carbonate particles are homogeneously dispersed as a filler within the polymer.

[0032] Japanese patent application JP 41 39020 A describes the polymerization of polybasic carboxylic acids or polyfunctional isocyanates in a calcium carbonate composition comprising colloidal or particulate calcium carbonate. Here, too, the calcium carbonate particles are homogeneously dispersed as a filler within the polymer.

[0033] The publication by M. Avella, S. Cosco, ML Di Lorenzo, E. Di Pace, ME Errico, "Influence of CaCO3 Nanoparticles Shape on Thermal and Crystallization Behavior of Isotactic Polypropylene based Nanocomposites," Journal of Thermal Analysis and Calorimetry, Vol. 80 (2005) 131-136, describes the influence of the shape of CaCO3 nanoparticles on the thermal and crystallization behavior of isotactic polypropylene-based nanocomposites. The calcium carbonate particles are homogeneously dispersed as a filler within the polymer.

[0034] The publication by S. Weihe, M. Wehmöller, C. Schiller, C. Rasche, H. Eufinger, M. Epple, "Formgebung degradierbarer Werkstoffe mit Hilfe der Verfahrenskette zur Fertigung individueller CAD / CAM-Implante Biomedizinische Technik / Biomedical Engineering, Band 46, Heft s1, Seiten 214-215" discloses an implant manufacturing process using melt pressing of polyglycolide-co-lactide (PGLA), poly-L-lactide (PLLA) and graded materials from several polymers and presses using a stainless steel mold.

[0035] Furthermore, a gassing process using poly-DL-lactide (PDLLA) and a Teflon mold is described. This process is based on gassing with CO₂ under high pressure at room temperature. The CO₂ is absorbed by the polymer, lowering its glass transition temperature. Upon pressure reduction, the amorphous PDLLA foams and flows precisely out of the mold. This process is intended to enable the incorporation of thermolabile substances, such as antibiotics and osteoinductive proteins, and is also applicable to other amorphous polymers, such as PGLA.

[0036] One disadvantage of conventional polylactic acid (PLA) implant materials is that they are not visible on X-rays. Therefore, monitoring treatment progress via X-ray is not possible.

[0037] Against this background, the present invention was based on the objective of providing the most efficient and cost-effective solution possible, particularly for the following problems: Firstly, possibilities were sought to specifically improve the properties of polymers, preferably thermoplastic polymers, especially polyamides and resorbable polymers, preferably resorbable polyesters, in particular poly-D-, poly-L- and / or poly-D,L-lactic acid, preferably with regard to their mechanical properties and / or their suitability for medical technology applications.

[0038] Furthermore, possibilities should be shown how calcium salts, in particular calcium carbonate, can be dispersed as homogeneously as possible in a polymer, preferably in a thermoplastic polymer, particularly preferably in a polyamide and / or in a resorbable polymer, preferably in a resorbable polyester, in particular in poly-D-, poly-L- and / or poly-D,L-lactic acid.

[0039] The solution according to the invention should be able to be implemented in the simplest and most cost-effective way possible.

[0040] Furthermore, the resulting polymers should be processable in the simplest possible way.

[0041] The primary focus was on achieving the best possible mechanical properties and pH stabilization, which are particularly advantageous for applications in the medical technology sector.

[0042] Furthermore, materials, especially for medical technology applications, were sought that exhibit the best possible resorbability.

[0043] A solution was particularly desired for the problem that resorbable polyesters, especially polylactic acid, are only conditionally suitable for laser sintering applications, as they are very difficult, if not impossible, to grind to particle sizes smaller than 150 µm, preferably smaller than 125 µm, particularly in the range of 50 µm to 70 µm. In this context, solutions were desirable that would minimize dust formation of the ground product and, in particular, allow its use for the production of microcomponents and its use in cleanrooms.

[0044] Furthermore, the properties of polymer foams, especially those for medical applications such as implants, should also be improved.

[0045] Finally, ways in which treatment progress can be determined and verified in the simplest possible manner when using implant materials should also be shown.

[0046] These and other unspecified problems that can be directly derived from the above context are solved by providing microstructured composite particles with all the features of the present claims. The dependent claims relating back to claim 1 describe particularly advantageous variants of the composite particles. Furthermore, particularly advantageous applications of the composite particles according to the invention are protected.

[0047] By making accessible microstructured composite particles obtainable through a process in which large particles are combined with small particles, where the large particles have a mean particle diameter in the range of 0.1 µm to 10 mm, If the mean particle diameter of the small particles is at most 1 / 10 of the mean particle diameter of the large particles, the large particles comprise at least one polymer, the small particles comprise at least one calcium salt, the small particles are arranged on the surface of the large particles and / or inhomogeneously distributed within the large particles, the small particles comprise precipitated calcium carbonate particles with a mean particle size in the range of 0.01 µm to 1.0 mm, and / or the large particles comprise at least one resorbable polyester with a number-average molecular weight in the range of 500 g / mol to 1,000,000 g / mol, it is possible, in a way that is not readily foreseeable, to solve the aforementioned problems in an extremely efficient and inexpensive manner.

[0048] Firstly, it is possible to selectively improve the properties of thermoplastically processable polymers, especially thermoplastic polymers, preferably polyamides and resorbable polymers, preferably resorbable polyesters, in particular poly-D-, poly-L- and / or poly-D,L-lactic acid, especially with regard to their mechanical properties and their suitability for medical applications, by adding the composite particles according to the invention as an additive to thermoplastically processable polymers, especially to thermoplastic polymers, preferably to polyamides and to resorbable polymers, preferably to resorbable polyesters, in particular to poly-D-, poly-L- and / or poly-D,L-lactic acid.

[0049] Furthermore, calcium salts, in particular calcium carbonate, can be dispersed extremely homogeneously in a polymer, preferably in a thermoplastic polymer, particularly preferably in a polyamide and / or in a resorbable polymer, preferably in a resorbable polyester, in particular in poly-D-, poly-L- and / or poly-D,L-lactic acid, in this way.

[0050] The resulting polymers can then be further processed in a comparatively simple manner.

[0051] When comparing the individual particles, the composite particles according to the invention are very uniform and are characterized by a very high homogeneity, both with regard to their composition and their structure.

[0052] Furthermore, the composite particles according to the invention, both as a single component and as an additive in a matrix polymer, generally exhibit improved mechanical properties and improved pH stabilization compared to the pure thermoplastic polymer or polymer mixture. These properties make them particularly interesting for applications in the medical technology sector.

[0053] Furthermore, the composite particles according to the invention exhibit very good resorbability, particularly in the human organism.

[0054] The composite particles according to the invention can be ground in a relatively simple manner. Dust generation is extremely low because the calcium salt, particularly calcium carbonate, reduces the adhesion of the polymer particles during grinding, resulting in a better grinding result. Furthermore, local overheating of the material being ground is avoided as much as possible, so that even thermally degradable polymers can be processed very easily. In addition, the separate addition of the individual components (calcium salt and polymer) is avoided, which also significantly reduces dust formation during processing.In summary, this approach enables the targeted adjustment of the particle size of the milled particles, their flow properties, their free-flowing properties, and their tendency to generate dust, and thus, above all, the use of the milled products in ultrathin surfaces and in dust-sensitive applications, particularly for the production of microcomponents and for use in cleanrooms. Furthermore, no tendency to generate dust is observed even with the unmilled composite particles. The solution according to the invention is therefore particularly suitable for the production of polylactic acid particles for rapid prototyping (additive manufacturing processes), especially for laser sintering applications, wherein the polylactic acid particles in this context preferably have an average particle size of less than 150 µm, more preferably less than 125 µm, and particularly in the range of 50 µm to 70 µm.

[0055] Furthermore, the properties of polymer foams, especially those for medical applications such as implants, are also significantly improved.

[0056] Furthermore, the use of the composite particles according to the invention in implant materials also enables a comparatively simple check and verification of the treatment progress, since the composite particles according to the invention are visible in X-rays and thus the implant in the body can be directly observed by X-ray.

[0057] The present invention relates accordingly to microstructured composite particles which are obtainable by a process in which large particles are combined with small particles.

[0058] In the present invention, the term microstructure refers to the microscopic properties of a material. These include, among other things, the resolvable fine structure and the microstructure. These properties are not present in liquids or gases, where the individual atoms or molecules exist in a disordered state. Amorphous solids typically exhibit short-range structural order in the region of neighboring atoms, but no long-range order. Crystalline solids, on the other hand, exhibit an ordered lattice structure not only in the short-range but also in the long-range.

[0059] Within the scope of the present invention, the large particles comprise at least one resorbable polyester.

[0060] The term "thermoplastic polymer"A thermoplastic polymer is a plastic that can be deformed (thermoplastically) within a specific temperature range, preferably between 25°C and 350°C. This process is reversible, meaning it can be repeated indefinitely by cooling and reheating the material to a molten state, as long as overheating does not cause thermal decomposition. This distinguishes thermoplastic polymers from thermosets and elastomers.

[0061] The term "Biopolymer"The term refers to a material made from biogenic raw materials (renewable resources) and / or is biodegradable (biogenic and / or biodegradable polymer). This includes bio-based biopolymers, which may or may not be biodegradable, as well as petroleum-based polymers that are biodegradable. This distinguishes them from conventional, petroleum-based materials or plastics, which are not biodegradable, such as polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC).

[0062] The term "Rubber" Rubber refers to a high-molecular-weight, uncrosslinked polymeric material with rubber-like elastic properties at room temperature (25°C). At higher temperatures or under the influence of deformation forces, rubber exhibits increasingly viscous flow, thus enabling it to be shaped under suitable conditions.

[0063] Rubber-elastic behavior is characterized by a relatively low shear modulus and a rather weak temperature dependence. It is caused by changes in entropy. Stretching forces the rubber-elastic material into a more ordered configuration, which leads to a decrease in entropy. After the force is removed, the polymers therefore return to their original position and the entropy increases again.

[0064] The term "Polyurethane" Polyurethane (PU, DIN abbreviation: PUR) refers to a plastic or synthetic resin that is formed by the polyaddition reaction of diols or polyols with polyisocyanates. The urethane group is characteristic of a polyurethane.

[0065] The term "resorption" (from Latin resorbere = "to absorb") refers to the uptake of substances in biological systems, especially in the human organism.

[0066] Of particular interest are materials that can be used for the production of resorbable implants.

[0067] According to the invention, particularly preferred resorbable polymers comprise repeating units of lactic acid, hydroxybutyric acid, and / or glycolic acid, preferably lactic acid and / or glycolic acid, and especially lactic acid. Polylactic acids are particularly preferred. Furthermore, the use of poly(dioxanone) is also particularly advantageous.

[0068] Here, "polylactic acid" refers to polymers composed of lactic acid units. Such polylactic acids are typically produced by the condensation of lactic acids, but can also be obtained through the ring-opening polymerization of lactides under suitable conditions.

[0069] Particularly suitable resorbable polymers according to the invention include poly(glycolide-co-L-lactide), poly(L-lactide), poly(L-lactide-co-ε-caprolactone), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide-co-glycolide) and poly(dioxanone). Such polymers are commercially available, for example, from Boehringer Ingelheim Pharma KG (Germany) under the trade names Resomer® < GL 903, Resomer® < L 206 S, Resomer® < L 207 S, Resomer® < L 209 S, Resomer® < L 210, Resomer® < L 210 S, Resomer® < LC 703 S, Resomer® < LG 824 S, Resomer® < LG 855 S, Resomer® < LG 857 S, Resomer® < LR 704 S, Resomer® < LR 706 S, Resomer® < LR 708, Resomer® < LR 927 S, Resomer® < RG 509 S and Resomer® < X 206 S.

[0070] For the purposes of the present invention, particularly advantageous resorbable polymers, preferably resorbable polyesters, preferably lactic acid polymers, in particular poly-D-, poly-L- or poly-D,L-lactic acids, have a number-average molecular weight (Mn), preferably determined by gel permeation chromatography against narrowly divided polystyrene standards or by end-group titration, greater than 500 g / mol, preferably greater than 1,000 g / mol, particularly preferably greater than 5,000 g / mol, expediently greater than 10,000 g / mol, and in particular greater than 25,000 g / mol. On the other hand, the number-average molecular weight of preferred resorbable polymers is less than 1,000,000 g / mol, expediently less than 500,000 g / mol, advantageously less than 100,000 g / mol, and in particular at most 50,000 g / mol. A numerical average of the molecular weight in the range of 500 g / mol to 50,000 g / mol has proven particularly useful within the scope of the present invention.

[0071] The weight mean molecular weight (Mw) of preferred resorbable polymers, preferably resorbable polyesters, advantageously lactic acid polymers, in particular poly-D-, poly-L- or poly-D,L-lactic acids, preferably determined by gel permeation chromatography against narrowly divided polystyrene standards, is preferably in the range of 750 g / mol to 5,000,000 g / mol, more preferably in the range of 750 g / mol to 1,000,000 g / mol, more preferably in the range of 750 g / mol to 500,000 g / mol, and more preferably in the range of 750 g / mol to 250,000 g / mol, and the polydispersity of these polymers is advantageously in the range of 1.5 to 5.

[0072] The inherent viscosity of particularly suitable, resorbable polymers, preferably resorbable polyesters, preferably lactic acid polymers, in particular poly-D-, poly-L- or poly-D,L-lactic acids, measured in chloroform at 25°C, 0.1% polymer concentration, is in the range of 0.5 dl / g to 8.0 dl / g, preferably in the range of 0.8 dl / g to 7.0 dl / g, and particularly in the range of 1.5 dl / g to 3.2 dl / g.

[0073] Furthermore, the inherent viscosity of particularly suitable, resorbable polymers, preferably resorbable polyesters, preferably lactic acid polymers, in particular poly-D-, poly-L- or poly-D,L-lactic acids, measured in hexafluoro-2-propanol at 30°C, 0.1% polymer concentration, is in the range of 1.0 dl / g to 2.6 dl / g, particularly in the range of 1.3 dl / g to 2.3 dl / g.

[0074] Furthermore, within the scope of the present invention, resorbable thermoplastic polyesters with a glass transition temperature greater than 20°C, preferably greater than 25°C, more preferably greater than 30°C, particularly preferably greater than 35°C, and especially greater than 40°C, are extremely advantageous. In a particularly preferred embodiment of the present invention, the glass transition temperature of the polymer is in the range of 35°C to 55°C, particularly in the range of 40°C to 50°C.

[0075] Furthermore, resorbable polyesters are particularly suitable which have a melting temperature greater than 50°C, preferably of at least 60°C, preferably of greater than 150°C, particularly preferably in the range of 160°C to 210°C, especially in the range of 175°C to 195°C.

[0076] The glass transition temperature and the melting temperature of the polymer are preferably determined using differential scanning calorimetry.

[0077] Calorimetry (DSC for short). The following procedure has proven particularly effective in this context: The DSC measurement is performed under nitrogen on a Mettler-Toledo DSC 30S. Calibration is preferably carried out with indium. The measurements are preferably performed under dry, oxygen-free nitrogen (flow rate: preferably 40 ml / min). The sample weight is preferably chosen to be between 15 mg and 20 mg. The samples are first heated from 0°C to preferably a temperature above the melting point of the polymer under investigation, then cooled to 0°C and heated a second time from 0°C to the aforementioned temperature at a heating rate of 10°C / min.

[0078] Within the scope of the present invention, the small particles of the composite particles comprise at least one calcium salt.

[0079] However, it preferably consists of at least one calcium carbonate, in particular at least one precipitated calcium carbonate.

[0080] The shape of the calcium salt particles, preferably the calcium carbonate particles, in particular the precipitated calcium carbonate particles, is not subject to any further restrictions and can be tailored to the specific application. However, scalenohedral, rhombohedral, needle-shaped, plate-shaped, or spherical particles are preferred. In a particularly preferred embodiment of the present invention, spherical calcium salt particles, preferably calcium carbonate particles, and in particular spherical precipitated calcium carbonate particles, are used, since these typically exhibit an isotropic property profile. Accordingly, the resulting composite particles are also advantageously characterized by a property profile that is as isotropic as possible.

[0081] The aspect ratio of the calcium salt particles, preferably of the calcium carbonate particles, in particular of the precipitated calcium carbonate particles, is preferably less than 5, more preferably less than 4, more preferably less than 3, more favorably less than 2, even more preferably less than 1.5, most preferably in the range of 1.0 to 1.25, more preferably less than 1.1, more preferably less than 1.05.

[0082] The aspect ratio of calcium salt particles, in this context, refers to the quotient of the maximum and minimum particle diameters. It is preferably determined as a mean value (number-average) using electron microscopy. For spherical calcium salt particles, only particles with a size in the range of 0.1 µm to 30.0 µm are preferably considered. For rhombohedral calcium salt particles, only particles with a size in the range of 0.1 µm to 20.0 µm are preferably considered. For other calcium salt particles, only particles with a size in the range of 0.1 µm to 2.0 µm are preferably considered.

[0083] Furthermore, preferably at least 90%, and more favorably at least 95%, of all particles have an aspect ratio of less than 5, more preferably less than 4, more preferably less than 3, more favorably less than 2, even more preferably less than 1.5, and most preferably in the range of 1.0 to 1.25, more preferably less than 1.1, and more favorably less than 1.05.

[0084] Spherical calcium salt particles, preferably predominantly single-particle, remain particularly advantageous. Minor deviations from a perfect spherical shape are acceptable as long as the particle properties are not fundamentally altered. Thus, the particle surface may exhibit occasional defects or additional deposits.

[0085] In a particularly preferred embodiment of the present invention, the calcium salt particles, preferably the calcium carbonate particles, and in particular the precipitated calcium carbonate particles, are preferably spherical and essentially amorphous. The term "amorphous" here refers to those calcium salt modifications in which the atoms do not form ordered structures, at least partially, but rather an irregular pattern, and therefore only possess short-range order, but not long-range order. These are to be distinguished from crystalline modifications of the calcium salt, such as calcite, vaterite, and aragonite, in which the atoms exhibit both short-range and long-range order.

[0086] In this preferred embodiment of the present invention, the presence of crystalline components is not categorically excluded. Preferably, the proportion of crystalline calcium salts, in particular crystalline calcium carbonate, is less than 50 wt.%, more preferably less than 30 wt.%, most preferably less than 15 wt.%, and more preferably less than 10 wt.%. In a particularly preferred embodiment of the present invention, the proportion of crystalline calcium salts, in particular crystalline calcium carbonate, is less than 8.0 wt.%, more preferably less than 6.0 wt.%, expediently less than 4.0 wt.%, more preferably less than 2.0 wt.%, and most preferably less than 1.0 wt.%, and more preferably less than 0.5 wt.%, in each case based on the total weight of the calcium salt.

[0087] X-ray diffraction with an internal standard, preferably quartz, in conjunction with Rietveld refinement has proven particularly effective for determining the amorphous and crystalline components.

[0088] In this preferred embodiment of the present invention, the calcium salt particles, preferably the preferably amorphous calcium carbonate particles, are advantageously stabilized by at least one substance, in particular at least one surfactant, which is preferably arranged on the surface of the calcium salt particles, especially on the surface of the preferably spherical calcium carbonate particles. For the purposes of the present invention, "surfactants" expediently denote organic compounds that strongly accumulate at interfaces (water / calcium salt particles, preferably calcium carbonate particles) when dissolved and thereby reduce the surface tension, preferably measured at 25°C. For further details, reference is made to the technical literature, in particular to Römpp-Lexikon Chemie / Ed. Jürgen Falbe; Manfred Regitz. Rev. Von Eckard Amelingmeier; Stuttgart, New York; Thieme; Volume 2: Cm-G; 10.Edition (1997); keyword: "surface-active substances", referenced.

[0089] Preferably the substance, in particular the surfactant, has a molar mass greater than 100 g / mol, preferably greater than 125 g / mol, in particular greater than 150 g / mol, and conforms to the formula RX n .

[0090] The term R represents a residue comprising at least 1, preferably at least 2, preferably at least 4, particularly preferably at least 6, in particular at least 8, carbon atoms, preferably an aliphatic or cycloaliphatic residue which may optionally include further residues X and which may optionally have one or more ether linkages.

[0091] The remainder X represents a group comprising at least one oxygen atom and at least one carbon atom, sulfur atom, phosphorus atom and / or nitrogen atom, preferably at least one phosphorus atom and / or at least one carbon atom. The following groups are particularly preferred: Carboxylic acid groups -COOH, carboxylate groups ~COO-< , sulfonic acid groups ~SO3H, sulfonate groups ~SO3-< , hydrogen sulfate groups ~OSO3H, sulfate groups ~OSO3-< , phosphonic acid groups ~PO3H2, phosphonate groups ~PO3H-< , ~PO32-< , amino groups ~NR1< R2< and ammonium groups ~N+< R1< R2< R3< , especially carboxylic acid groups, carboxylate groups, phosphonic acid groups and phosphonate groups.

[0092] In this context, the substituents R1<, R2<, and R3< independently represent either hydrogen or an alkyl group with 1 to 5 carbon atoms. One of the substituents R1<, R2<, and R3< can also be a substituent R.

[0093] Preferred counterions for the aforementioned anions are metal cations, in particular alkali metal cations, preferably Na+ and K+, as well as ammonium ions.

[0094] Preferred counterions for the aforementioned cations are hydroxyl ions, hydrogen carbonate ions, carbonate ions, hydrogen sulfate ions, sulfate ions and halide ions, in particular chloride and bromide ions.

[0095] n represents a preferably integer in the range of 1 to 20, preferably in the range of 1 to 10, and in particular in the range of 1 to 5.

[0096] Substances particularly suitable for the purposes of the present invention include alkyl carboxylic acids, alkyl carboxylates, alkyl sulfonic acids, alkyl sulfonates, alkyl sulfates, alkyl ether sulfates with preferably 1 to 4 ethylene glycol ether units, fatty alcohol ethoxylates with preferably 2 to 20 ethylene glycol ether units, alkylphenol ethoxylates, optionally substituted alkylphosphonic acids, optionally substituted alkylphosphonates, sorbitan fatty acid esters, alkyl polyglucosides, N-methylglucamides, homo- and copolymers of acrylic acid as well as their corresponding salt forms and block copolymers.

[0097] A first group of particularly advantageous substances are, if applicable, substituted alkylphosphonic acids, especially amino-tri-(methylenephosphonic acid), 1-hydroxyethylene-(1,1-diphosphonic acid), ethylenediamine-tetra-(methylenephosphonic acid), hexamethylenediamine-tetra-(methylenephosphonic acid), diethylenetriamine-penta-(methylenephosphonic acid), and, if applicable, substituted alkylphosphonates, especially of the aforementioned acids. These compounds are known as multifunctional sequestrants for metal ions and stone inhibitors.

[0098] Furthermore, homo- and copolymers, preferably homopolymers, of acrylic acid and their corresponding salt forms have proven particularly effective, especially those with a weight average molecular weight in the range of 1,000 g / mol - 10,000 g / mol.

[0099] Furthermore, the use of block copolymers, preferably double hydrophilic block copolymers, especially polyethylene oxide or polypropylene oxide, is particularly advantageous.

[0100] The proportion of the preferably surfactant substances can, in principle, be freely chosen and specifically adjusted for the respective application. However, it is preferably in the range of 0.1 wt.% to 5.0 wt.%, in particular in the range of 0.3 wt.% to 1.0 wt.%, based on the calcium salt content, especially the CaCO3 content, of the particles.

[0101] The production of the preferably spherical, preferably amorphous calcium salt particles, in particular the calcium carbonate particles, can be carried out in a manner known per se, e.g. by hydrolysis of dialkyl carbonate or of alkylene carbonate in a solution comprising calcium cations.

[0102] The production of non-stabilized, spherical calcium carbonate particles is described in detail, for example, in patent application WO 2008 / 122358, the disclosure of which, in particular with regard to especially advantageous variants of the production of such non-stabilized, spherical calcium carbonate particles,

[0103] The hydrolysis of dialkyl carbonate or alkylene carbonate is conveniently carried out in the presence of a hydroxide.

[0104] For the purposes of the present invention, preferred substances comprising Ca²⁺ ions are calcium halides, preferably CaCl₂, CaBr₂, and especially CaCl₂, as well as calcium hydroxide. In a first particularly preferred embodiment of the present invention, CaCl₂ is used. In a further particularly preferred embodiment of the present invention, Ca(OH)₂ is used.

[0105] In a first particularly preferred embodiment of the present invention, a dialkyl carbonate is used. Particularly suitable dialkyl carbonates comprise 3 to 20, preferably 3 to 9, carbon atoms, in particular dimethyl carbonate, diethyl carbonate, di-n-propyl carbonate, di-isopropyl carbonate, di-n-butyl carbonate, di-sec-butyl carbonate and di-tert-butyl carbonate, with dimethyl carbonate being particularly preferred in this context.

[0106] In a further particularly preferred embodiment of the present invention, an alkylene carbonate is reacted. Particularly suitable alkylene carbonates comprise 3 to 20, preferably 3 to 9, particularly preferably 3 to 6, carbon atoms and especially include compounds comprising a ring of 3 to 8, preferably 4 to 6, particularly 5, atoms, with preferably 2 oxygen atoms and the rest carbon atoms. Propylene carbonate (4-methyl-1,3-dioxolane) has proven particularly suitable in this context.

[0107] Alkali metal hydroxides, especially NaOH, and calcium hydroxide have proven particularly suitable as hydroxides. In a first particularly preferred embodiment of the present invention, NaOH is used. In a further particularly preferred embodiment of the present invention, Ca(OH)₂ is used.

[0108] Furthermore, the molar ratio of Ca 2+< , preferably calcium chloride, to OH -< , preferably alkali metal hydroxide, in the reaction mixture is preferably greater than 0.5 : 1 and particularly preferably in the range of >0.5 : 1 to 1 : 1, especially in the range of 0.6 : 1 to 0.9 : 1.

[0109] The molar ratio of Ca²⁺, preferably calcium chloride, to dialkyl carbonate and / or alkylene carbonate in the reaction mixture is advantageously in the range of 0.9 : 1.5 to 1.1 : 1, particularly preferably in the range of 0.95 : 1 to 1 : 0.95. In a particularly advantageous embodiment of the present invention, the dialkyl carbonate and / or the alkylene carbonate and the Ca²⁺, in particular the calcium chloride, are used in equimolar proportions.

[0110] In a first, particularly preferred embodiment of the present invention, Ca(OH)₂ is not used as the OH⁻ source. The components for the reaction are advantageously used in the following concentrations: a) Ca 2+< : >10 mmol / l to 50 mmol / l, preferably 15 mmol / l to 45 mmol / l, in particular 17 mmol / l to 35 mmol / l; b) Dialkyl carbonate and / or alkylene carbonate: >10 mmol / l to 50 mmol / l, preferably 15 mmol / l to 45 mmol / l, in particular 17 mmol / l to 35 mmol / l; c) OH -< : 20 mmol / l to 100 mmol / l, preferably 20 mmol / l to 50 mmol / l, particularly preferably 25 mmol / l to 45 mmol / l, especially 28 mmol / l to 35 mmol / l.

[0111] The respective concentration values ​​refer to the concentrations of the mentioned components in the reaction mixture.

[0112] In a further particularly preferred embodiment of the present invention, Ca(OH)₂, preferably lime milk, especially saturated lime milk, is used as the OH⁻ source. The components for the reaction are advantageously used in the following concentrations: a) Ca(OH)2: >5 mmol / l to 25 mmol / l, preferably 7.5 mmol / l to 22.5 mmol / l, in particular 8.5 mmol / l to 15.5 mmol / l; b) Dialkyl carbonate and / or Alkylene carbonate: >5 mmol / l to 25 mmol / l, preferably 7.5 mmol / l to 22.5 mmol / l, in particular 8.5 mmol / l to 15.5 mmol / l.

[0113] The respective concentration values ​​refer to the concentrations of the mentioned components in the reaction mixture.

[0114] The reaction of the components is preferably carried out at a temperature in the range of 15°C to 30°C.

[0115] The specific size of the calcium salt particles, especially the calcium carbonate particles, can be controlled in a known manner via supersaturation.

[0116] Under the conditions mentioned above, the calcium salt particles, especially the calcium carbonate particles, precipitate out of the reaction mixture.

[0117] The stabilization of the preferably amorphous calcium salt particles, in particular the preferably amorphous calcium carbonate particles, is expediently achieved by adding the preferably surfactant to the reaction mixture.

[0118] This addition of the substance should only take place after the reaction to form the calcium salt particles, in particular the calcium carbonate particles, has begun, i.e., only after the addition of the reactants, preferably at least 1 minute, more preferably at least 2 minutes, expediently at least 3 minutes, particularly preferably at least 4 minutes, and especially at least 5 minutes, after mixing the reactants. Furthermore, the timing of the addition should be chosen such that the preferably surfactant is added shortly before the end of the precipitation and as shortly as possible before the start of the conversion of the preferably amorphous calcium salt, in particular the amorphous calcium carbonate, into a crystalline modification, since in this way the yield and purity of the stabilized, spherical, amorphous calcium salt particles"This can be maximized. If the preferably surfactant is added earlier, a bimodal product is generally obtained that, in addition to the desired stabilized, spherical, amorphous calcium salt particles, also includes ultrafine, amorphous calcium salt particles as a byproduct. If the preferably surfactant is added later, the conversion of the desired "stabilized calcium salt particles" into crystalline modifications.

[0119] For this reason, the preferably surfactant is preferably added at a pH of less than or equal to 11.5, more preferably less than or equal to 11.3, and particularly less than or equal to 11.0. Addition at a pH in the range of 11.5 to 10.0, preferably in the range of 11.3 to 10.5, and particularly in the range of 11.0 to 10.8, is especially advantageous, in each case measured at the reaction temperature, preferably at 25°C.

[0120] The resulting stabilized, preferably spherical, amorphous calcium salt particles can be dehydrated and dried in a known manner, e.g., by centrifugation. Washing with acetone and / or drying in a vacuum drying oven is no longer strictly necessary.

[0121] Through drying, the "stabilized calcium salt particles", "calcium salt particles with low structural water content", in particular "calcium carbonate particles with low structural water content", available.

[0122] For the purposes of the present invention, the calcium salt particles obtained are preferably dried such that they have the desired residual water content. A method has proven particularly effective in which the calcium salt particles are preferably first pre-dried at a temperature up to 150°C and then dried, preferably at a temperature in the range of greater than 150°C to 250°C, more preferably in the range of 170°C to 230°C, more preferably in the range of 180°C to 220°C, and particularly in the range of 190°C to 210°C. Drying is preferably carried out in a circulating air drying oven. The calcium salt particles are expediently dried for at least 3 hours, more preferably at least 6 hours, and more preferably at least 20 hours.

[0123] In a further particularly preferred embodiment of the present invention, the preferably precipitated calcium salt particles, in particular the preferably precipitated calcium salt particles, are substantially crystalline, in particular substantially calcitic. However, in this preferred embodiment of the present invention, the presence of other, in particular amorphous, components is not categorically excluded. Preferably, the proportion of other non-crystalline calcium salt modifications, in particular other non-crystalline calcium carbonate modifications, is less than 50 wt.%, more preferably less than 30 wt.%, and most preferably less than 15 wt.%, and in particular less than 10 wt.%. Furthermore, the proportion of non-calcitic calcium carbonate modifications is preferably less than 50 wt.%, more preferably less than 30 wt.%, and in particular less than 15 wt.%, and in particular less than 10 wt.%.

[0124] The mean diameter of the preferably precipitated calcium salt particles, in particular the preferably precipitated calcium carbonate particles, can in principle be freely chosen. It is preferably in the range of 0.05 µm to 30.0 µm, and particularly in the range of 0.1 µm to 15.0 µm.

[0125] For amorphous calcium salt particles, especially for amorphous calcium carbonate particles, the mean diameter of the calcium salt particles is advantageously in the range of 0.05 µm to 2.0 µm, preferably less than 1.75 µm, particularly preferably less than 1.5 µm, and especially less than 1.2 µm. Furthermore, in this case, the mean particle diameter is advantageously greater than 0.1 µm, preferably greater than 0.2 µm, and especially greater than 0.3 µm.

[0126] For scalenohedral calcium salt particles, in particular for scalenohedral calcium carbonate particles, the mean diameter of the calcium salt particles is advantageously in the range of 0.05 µm to 2.0 µm, preferably less than 1.75 µm, particularly preferably less than 1.5 µm, and especially less than 1.2 µm. Furthermore, the mean particle diameter in this case is advantageously greater than 0.1 µm, preferably greater than 0.2 µm, and especially greater than 0.3 µm.

[0127] Furthermore, scalenohedral calcium salt particles, especially calcium carbonate particles, have proven particularly suitable, preferably having a mean diameter in the range of 1.0 µm to 5.0 µm, preferably less than 4.5 µm, particularly preferably less than 4.0 µm, and especially less than 3.5 µm. In this case, the mean particle diameter is also preferably greater than 1.5 µm, preferably greater than 2.0 µm, and especially greater than 3.0 µm.

[0128] For rhombohedral calcium salt particles, in particular for rhombohedral calcium carbonate particles, the mean diameter of the calcium salt particles is advantageously in the range of 0.05 µm to 2.0 µm, preferably less than 1.75 µm, particularly preferably less than 1.5 µm, and especially less than 1.2 µm. Furthermore, the mean particle diameter in this case is advantageously greater than 0.1 µm, preferably greater than 0.2 µm, and especially greater than 0.3 µm.

[0129] Furthermore, rhombohedral calcium salt particles, in particular calcium carbonate particles, have also proven particularly suitable, which preferably have a mean diameter in the range of 1.0 µm to 20.0 µm, preferably less than 18.0 µm, particularly preferably less than 16.0 µm, and especially less than 14.0 µm.

[0130] Furthermore, the mean particle diameter in this case is preferably greater than 2.5 µm, preferably greater than 4.0 µm, and in particular greater than 6.0 µm.

[0131] For needle-shaped calcium salt particles, in particular for needle-shaped calcium carbonate particles, the mean diameter of the calcium salt particles is advantageously in the range of 0.05 µm to 2.0 µm, preferably less than 1.5 µm, particularly preferably less than 1.0 µm, and especially less than 0.75 µm. Furthermore, in this case, the mean particle diameter is advantageously greater than 0.1 µm, preferably greater than 0.2 µm, and especially greater than 0.3 µm.

[0132] For platelet-shaped calcium salt particles, in particular for platelet-shaped calcium carbonate particles, the mean diameter of the calcium salt particles is advantageously in the range of 0.05 µm to 2.0 µm, preferably less than 1.75 µm, particularly preferably less than 1.5 µm, and especially less than 1.2 µm. Furthermore, in this case, the mean particle diameter is advantageously greater than 0.1 µm, preferably greater than 0.2 µm, and especially greater than 0.3 µm.

[0133] For spherulitic (spherical) calcium salt particles, especially for spherical calcium carbonate particles, a mean diameter in the range of 1.0 µm to 30.0 µm, preferably less than 20.0 µm, preferably less than 18.0 µm, particularly preferably less than 16.0 µm, and especially less than 14.0 µm, has proven particularly advantageous. Furthermore, in this case, the mean particle diameter is advantageously greater than 2.5 µm, preferably greater than 4.0 µm, and especially greater than 6.0 µm.

[0134] The aforementioned average particle sizes of the calcium salt particles, in particular the calcium carbonate particles, are expediently determined within the scope of the present invention by evaluating scanning electron microscope images (SEM images), preferably considering only particles with a size of at least 0.01 µm and calculating a numerical average over preferably at least 20, and particularly preferably at least 40 particles. Furthermore, sedimentation analysis methods have also proven particularly effective, especially for needle-shaped calcium salt particles, with the use of a Sedigraph 5100 (Micromeritics GmbH) being particularly advantageous in this context.

[0135] For non-spherical calcium salt particles, the particle size equivalent to a sphere is preferably used as a reference.

[0136] The size distribution of the calcium salt particles is comparatively narrow and preferably such that at least 90.0 wt.% of all calcium salt particles, preferably all calcium carbonate particles, have a particle diameter in the range of mean particle diameter -50%, preferably in the range of mean particle diameter -40%, particularly in the range of mean particle diameter -30% to mean particle diameter +70%, preferably mean particle diameter +60%, and particularly mean particle diameter +50%. The size distribution is preferably determined by scanning tunneling microscopy.

[0137] The form factor of the calcium salt particles, preferably the calcium carbonate particles, defined here as the quotient of minimum particle diameter and maximum particle diameter, is advantageously greater than 0.90 for at least 90%, preferably greater than 0.95 for at least 95% of all particles. In this context, for spherical calcium salt particles, preferably only particles with a particle size in the range of 0.1 µm to 30.0 µm are considered. For rhombohedral calcium salt particles, preferably only particles with a particle size in the range of 0.1 µm to 20.0 µm are considered. For other calcium salt particles, preferably only particles with a particle size in the range of 0.1 µm to 2.0 µm are considered.

[0138] The calcium salt particles, in particular the calcium carbonate particles, are advantageously characterized by a comparatively low water content. Based on their total weight, they have a water content (residual moisture at 200°C) of at most 5.0 wt.%, preferably at most 2.5 wt.%, more preferably at most 1.0 wt.%, particularly preferably at most 0.5 wt.%, even more preferably less than 0.4 wt.%, expediently less than 0.3 wt.%, advantageously less than 0.2 wt.%, and in particular at most 0.1 wt.%.

[0139] Within the scope of the present invention, the water content of the calcium salt particles, in particular the calcium carbonate particles, is preferably determined by thermogravimetry, wherein the measurement is preferably carried out under nitrogen (nitrogen flow rate preferably 20 ml / min) and expediently over the temperature range from 40°C or lower to 250°C or higher. Furthermore, the measurement is preferably carried out at a heating rate of 10°C / min.

[0140] When amorphous calcium carbonate particles are used as calcium salt particles within the scope of the present invention, they advantageously have a low structural water content. This content is preferably less than 5 mol, more preferably less than 3 mol, particularly preferably less than 1 mol, and especially less than 0.5 mol of structural water per mol of calcium carbonate. In a particularly preferred embodiment of the present invention, the amorphous calcium carbonate particles do not contain any structural water.

[0141] The specific surface area of ​​the calcium salt particles, in particular the calcium carbonate particles, is preferably in the range of 0.1 m² / g to 100 m² / g, particularly preferably in the range of 0.1 m² / g to 20.0 m² / g, and particularly in the range of 4.0 m² / g to 12.0 m² / g. For rhombohedral calcium salt particles, in particular for rhombohedral calcium carbonate particles, the specific surface area, in a particularly preferred embodiment of the present invention, is less than 1.0 m² / g, preferably less than 0.75 m² / g, and in particular less than 0.5 m² / g, wherein the mean diameter of the rhombohedral calcium salt particles, in particular the rhombohedral calcium carbonate particles, is advantageously greater than 2.5 µm, preferably greater than 4.0 µm, and in particular greater than 6.0 µm.

[0142] For spherical calcium salt particles, in particular for spherical calcium carbonate particles, which preferably have a mean diameter greater than 2.5 µm, more preferably greater than 4.0 µm, and more particularly greater than 6.0 µm, the specific surface area, in a particularly preferred embodiment of the present invention, is less than 3.0 m² / g, more preferably less than 2.0 m² / g, and more particularly less than 1.5 m² / g. Furthermore, in this case, the specific surface area is advantageously greater than 0.25 m² / g, more preferably greater than 0.5 m² / g, and more particularly greater than 0.75 m² / g.

[0143] In this context, calcium salt particles, especially calcium carbonate particles, are particularly preferred, as their specific surface area remains relatively constant during drying and changes preferably by a maximum of 200%, preferably by a maximum of 150%, and particularly by a maximum of 100%, respectively, relative to the initial value.

[0144] The basicity of the calcium salt particles, especially the calcium carbonate particles, is comparatively low. Their pH value, measured according to EN ISO 787-9, is preferably less than 11.5, more preferably less than 11.0, and particularly less than 10.5.

[0145] For the purposes of the present invention, particularly advantageous calcium salts include, in addition to calcium carbonate, calcium phosphates, in particular Ca 3 (PO 4 ) 2 , CaHPO 4 , Ca(H 2 PO 4 ) 2 and / or Ca 5 (PO 4 ) 3 (OH).

[0146] Furthermore, calcium salt mixtures are also particularly suitable. These preferably comprise at least one calcium carbonate, in particular a precipitated calcium carbonate, and at least one calcium phosphate, in particular Ca3(PO4)2, CaHPO4, Ca(H2PO4)2 and / or Ca5(PO4)3(OH).

[0147] The weight ratio of calcium salt, in particular calcium carbonate, to calcium phosphate is preferably in the range of 99:1 to 1:99, and particularly in the range of 50:50 to 99:1.

[0148] Within the scope of the present invention, the microstructured composite particles are obtainable by a process in which large particles are combined with small particles, wherein The large particles have a mean particle diameter in the range of 0.1 µm to 10 mm, preferably in the range of 0.5 µm to 2.0 mm, particularly in the range of 1.0 µm to 500.0 µm, the mean particle diameter of the small particles is at most 1 / 10 of the mean particle diameter of the large particles and is preferably in the range of 0.01 µm to 1.0 mm, preferably in the range of 0.02 µm to 200 µm, expediently in the range of 0.05 µm to 30.0 µm, particularly in the range of 0.1 µm to 15.0 µm.

[0149] The small particles are arranged on the surface of the large particles and / or inhomogeneously distributed within the large particles.

[0150] An "inhomogeneous" distribution of the small particles within the large particles here means a non-homogeneous (uniform) distribution of the small particles within the large particles. Preferably, there is at least one first region within the composite particles comprising at least two, preferably at least three, preferably at least four, and in particular at least five small particles, and at least one other region within the composite particles that has the same volume and shape as the first region but comprises a different number of small particles.

[0151] Furthermore, the weight ratio of polymer to calcium salt, preferably calcium carbonate, particularly precipitated calcium carbonate, in the interior of the particles is greater than the weight ratio of polymer to calcium salt, preferably calcium carbonate, particularly precipitated calcium carbonate, in the exterior of the particles. Advantageously, the weight ratio of polymer to calcium salt, preferably calcium carbonate, particularly precipitated calcium carbonate, in the interior of the particles is greater than 50:50, more preferably greater than 60:40, more favorably greater than 70:30, particularly preferably greater than 80:20, even more preferably greater than 90:10, most preferably greater than 95:5, and particularly greater than 99:1.Furthermore, the weight ratio of calcium salt, preferably calcium carbonate, in particular precipitated calcium carbonate, to polymer in the outer area of ​​the particles, preferably in the preferred outer area of ​​the particles, is greater than 50:50, preferably greater than 60:40, advantageously greater than 70:30, particularly preferably greater than 80:20, even more preferably greater than 90:10, most particularly preferably greater than 95:5, in particular greater than 99:1.

[0152] In this context, the particle interior refers to the region that has a maximum distance of r / 2 from the particle center, where the particle center preferably corresponds to the center of mass of the particle and where r corresponds to the radius of the compact spherical particle, which consists of the same components in the same proportions and with the same densities.

[0153] The outer region of the particles refers to the region that is at a distance greater than r / 2 from the particle's center. The preferred outer region of the particles refers to the region that is at a distance greater than 0.793r from the particle's center. The particle's center and r are defined as before.

[0154] For the purposes of the present invention, the composite particles are particularly preferred to be spherical. The mean diameter of the composite particles is preferably in the range of 0.1 µm to 12 mm, and particularly in the range of 0.5 µm to 2.4 mm.

[0155] In a particularly preferred embodiment of the present invention, the composite particles according to the invention comprise a core and a shell, wherein the core preferably comprises at least one polymer, in particular at least one thermoplastic polymer, and preferably has a mean diameter in the range of 0.1 µm to 10 mm, in particular in the range of 0.5 µm to 2 mm. The shell preferably comprises at least one calcium salt, more preferably at least one calcium carbonate, in particular at least one precipitated calcium carbonate, and preferably has a mean thickness of at most 20%, based on the core diameter.

[0156] The mean diameters of the composite particles, the large particles, and the small particles, as well as the aforementioned length dimensions, are advantageously determined according to the invention by means of microscopic images, optionally by means of electron microscopic images. Sedimentation analyses are also particularly advantageous for determining the mean diameters of the large and small particles, with the use of a Sedigraph 5100 (Micromeritics GmbH) being especially beneficial in this regard. For the composite particles, particle size analyses using laser diffraction have also proven particularly effective, with the use of a HELOS / BR laser diffraction sensor from Sympatec GmbH being particularly advantageous in this context. This sensor preferably comprises a RODOS dry disperser.

[0157] For non-spherical particles, the particle size equivalent to a sphere is preferably used.

[0158] Furthermore, unless otherwise stated, these specifications and all other information in this description refer to a temperature of 25°C.

[0159] The composite particles according to the invention are comparatively compact. Preferably, the proportion of interior regions of the particles having a density of less than 0.5 g / cm³, in particular less than 0.25 g / cm³, is less than 10.0%, preferably less than 5.0%, and in particular less than 1.0%, in each case based on the total volume of the composite particles.

[0160] The weight fraction of the calcium salt, preferably of the calcium carbonate, in particular of the precipitated calcium carbonate, based on the total weight of the composite particles, is preferably at least 0.1 wt.%, preferably at least 1.0 wt.%, particularly preferably at least 5.0 wt.%, and is expediently in the range of 5.0 wt.% to 50.0 wt.%, advantageously in the range of 10.0 wt.% to 30.0 wt.%, in particular in the range of 15.0 wt.% to 25.0 wt.%.

[0161] The weight fraction of the polymer, preferably the thermoplastic polymer, based on the total weight of the composite particles, is preferably at least 0.1 wt.%, preferably at least 1.0 wt.%, particularly preferably at least 5.0 wt.%, and is expediently in the range of 5.0 wt.% to 95.0 wt.%, advantageously in the range of 70.0 wt.% to 90.0 wt.%, in particular in the range of 75.0 wt.% to 85.0 wt.%.

[0162] The composite particles according to the invention are characterized, among other things, by a very good bond between the small and large particles. The strong bond between the small and large particles can preferably be verified by mechanically stressing the composite particles, in particular by shaking the composite particles with water at 25°C, preferably according to the procedure described in Organikum, 17th edition, VEB Deutscher Verlag der Wissenschaften, Berlin, 1988, section 2.5.2.1 "Shaking of solutions or suspensions", pages 56-57. The shaking time is preferably at least one minute, more preferably at least five minutes, and more preferably ten minutes, and preferably does not lead to a significant change in the shape, size, and / or composition of the composite particles. Particularly preferred after the shaking test are at least 60 wt%, more preferably at least 70 wt%, and more preferably at least 80 wt%.-%, particularly preferably at least 90 wt.%, preferably at least 95 wt.%, in particular at least 99 wt.% of the composite particles, are not altered with regard to their composition, their size and preferably their shape.

[0163] The production of the composite particles according to the invention can be carried out in a manner known per se, for example by a single-stage process, in particular by precipitation or coating, preferably by coating with ground material.

[0164] However, a particularly effective method involves bringing polymer particles and calcium salt particles into contact and bonding them together through the application of mechanical forces. This is expediently carried out in a suitable mixer or mill, especially an impact mill, pin mill, or ultrarotor mill. The rotor speed is preferably greater than 1 m / s, more preferably greater than 10 m / s, and particularly preferably greater than 25 m / s, especially in the range of 50 m / s to 100 m / s.

[0165] According to a particularly preferred embodiment of the present invention, this procedure results in the calcium salt particles penetrating the interior of the polymer particles and being covered as completely as possible by the polymer, so that they are not visible from the outside. Such particles can be processed and used like the polymer without calcium salt particles, but exhibit the improved properties of the composite particles according to the invention.

[0166] According to a further particularly preferred embodiment of the present invention, this procedure does not result in the calcium salt particles penetrating into the interior of the polymer particles, but rather the calcium salt particles are fixed to the surface of the polymer particles and are easily recognizable from the outside.

[0167] In a first particularly preferred embodiment of the present invention, the composite particles are produced in accordance with the procedure described in patent application JP62083029 A. Large particles (so-called parent particles) are coated on the surface with small particles (so-called baby particles). For this purpose, a surface modification device (“ Hybridizer The system comprises a high-speed rotor, a stator, and a spherical vessel, preferably including internal blades. The use of NARA hybridization systems, preferably with a rotor outer diameter of 118 mm, in particular a hybridization system designated NHS-0 or NHS-1 by NARA Machinery Co., Ltd., has proven particularly effective in this context.

[0168] The mother particles and the baby particles are mixed, preferably finely dispersed, and introduced into the hybridizer. There, the mixture is preferably further finely dispersed and preferably repeatedly subjected to mechanical forces, in particular impact forces, compression forces, frictional forces, and shear forces, as well as the mutual interactions of the particles, in order to uniformly embed the baby particles in the mother particles. Preferred rotor speeds are in the range of 50 m / s to 100 m / s, based on the circumferential speed.

[0169] For further details on this method, in particular regarding the most suitable embodiments, please refer to JP62083029 A .

[0170] In a further particularly preferred embodiment of the present invention, the composite particles are produced in accordance with the procedure described in patent application DE 42 44 254 A1. Accordingly, a method for producing composite particles by attaching a substance to the surface of a thermoplastic material is particularly advantageous if the thermoplastic material has an average particle diameter of 100 µm to 10 mm and the substance has a smaller particle diameter and better heat resistance than the thermoplastic material, especially if the method comprises the following steps: • First, heat the substance, which has a smaller particle diameter and better heat resistance than the thermoplastic material, to a temperature that is preferably not lower than the softening point of the thermoplastic material, while stirring in a device that preferably has a stirrer and a heating device; • Add the thermoplastic material to the device; and • Attach the substance with the better heat resistance to the surface of the thermoplastic material.

[0171] For further details on this method, in particular regarding the particularly suitable embodiments, reference is made to DE 42 44 254 A1.

[0172] In a further particularly preferred embodiment of the present invention, the composite particles are produced in accordance with the procedure described in patent application EP 0 922 488 A1 and / or in patent US 6,403,219 B1. Accordingly, a method for producing composite particles by attaching or bonding fine particles to the surface of a solid particle, which acts as a core, by applying an impact and subsequent growth of one or more crystals on the core surface is particularly advantageous.

[0173] For further details on this process, in particular regarding the particularly advantageous embodiments, reference is made to patent application EP 0 922 488 A1 and / or patent US 6,403,219 B1.

[0174] In a further particularly preferred embodiment of the present invention, the composite particles are subjected to fixation in accordance with the procedure described in patent application EP 0 523 372 A1. This is particularly advantageous for composite particles obtained in accordance with the method described in patent application JP62083029 A. The fixation of the composite particles is preferably carried out by thermal plasma spraying, preferably using a reduced pressure plasma spraying device, which preferably has a power output of at least 30 kW, in particular the device described in EP 0 523 372 A1.

[0175] For further details on this process, in particular regarding the particularly suitable embodiments, reference is made to patent application EP 0 523 372 A1.

[0176] The composite particles according to the invention are characterized by an excellent property profile. In addition to excellent mechanical properties, they exhibit very good dispersibility, outstanding grindability, extremely low dust tendency, and a comparatively high isotropy.

[0177] Furthermore, the presence of the calcium salt, preferably calcium carbonate, in the composite particles enables pH stabilization (buffering) in subsequent applications, particularly in polymers that contain acid groups or can release acids under certain conditions. Polylactic acid is one example.

[0178] Furthermore, the composite particles according to the invention may replace other, more expensive materials, thereby reducing the cost of the final product.

[0179] Further processing of the composite particles according to the invention can be carried out in a comparatively simple manner, since according to the solution of the invention only one component (the composite particles) and no longer two components (calcium salt and polymer) need to be processed. Dispersion problems are not observed due to the strong bond between the polymer and the calcium salt.

[0180] Furthermore, the microstructure, porosity, and permeability of the composite particles can be specifically controlled by selecting the proportions and sizes of the individual components. The consistently controllable permeability, porosity, and isotropy of the composite particles can, in turn, be used to specifically control the final structure of the resulting components, particularly their microstructure, porosity, and permeability.

[0181] The addition of further processing aids, in particular special solvents, is generally not required when processing the composite particles according to the invention. This expands the possible fields of application for the composite particles according to the invention, particularly in the pharmaceutical and food sectors.

[0182] The composite particles according to the invention can be used directly as such. However, due to their excellent property profile, the composite particles according to the invention are particularly suitable as an additive, especially preferably as a polymer additive, as an additive or starting material for the production of components, for applications in medical technology and / or microtechnology, and / or for the production of foamed objects. Particularly preferred medical technology applications preferably include resorbable implants. Particularly suitable areas of application include injection-molded screws, pressed plates, especially melt-pressed plates, foamed implants, and free-flowing powders for selective manufacturing processes, wherein in the latter case the overall particle size is preferably less than 3 mm and preferably greater than 0.5 µm.

[0183] As a polymer additive, the composite particles according to the invention are preferably added to at least one polymer, in particular a thermoplastic polymer, as a matrix polymer. Polymers that can also be used as components of the composite particles according to the invention are particularly preferred. To avoid repetition, reference is made to the above descriptions, especially regarding the preferred forms of the polymer. Particularly preferred matrix polymers include polyvinyl chloride (PVC), polyurethane (PU), silicone, polypropylene (PP), polyethylene (PE), and polylactic acid (PLA).

[0184] Within the scope of the present invention, the matrix polymer and the polymer of the composite particles are preferably miscible with each other at the application temperature, and particularly preferably chemically identical.

[0185] Particularly preferred compositions contain 40.0 wt.% to 99.9 wt.% of at least one matrix polymer and 0.1 wt.% to 50.0 wt.% of at least one composite particle according to the invention.

[0186] The composition can be prepared in a manner known per se by mixing the components.

[0187] The composition can then be further processed in the usual way, in particular granulated, ground, extruded, injection molded or foamed.

[0188] Furthermore, the composite particles according to the invention can be processed and / or used directly, i.e. without the addition of additional polymers.

[0189] The advantages of the composite particles according to the invention can be observed particularly during granulation, grinding, extrusion, injection molding, melt pressing and / or foaming of the composite particles.

[0190] Within the scope of the present invention, polymer foams are preferably produced by generating or introducing a gaseous phase into a composition comprising the composite particles according to the invention and optionally at least one matrix polymer. The aim is to distribute the gas as uniformly as possible within the composition in order to achieve a uniform and homogeneous foam structure. The gas can be introduced in various ways.

[0191] Preferably, the gas phase is generated by adding a blowing agent. Blowing agents are substances that release gases through chemical reactions (chemical blowing agents) or phase transitions (physical blowing agents). In foam extrusion or foam injection molding, the chemical blowing agent is added to the composition in the form of a masterbatch, or the physical blowing agent is injected directly into the melt under pressure. This injection is called direct gas injection and is used particularly in the processing of thermoplastic polymers.

[0192] Particularly for this application, it is advantageous if the composite particles according to the invention have a structure that allows a fluid substance, preferably the blowing agent, to penetrate the polymer and preferably to at least partially dissolve it. In composite particles with a core comprising at least one, preferably thermoplastic, polymer and a shell comprising at least one calcium salt, preferably at least one calcium carbonate, in particular at least one precipitated calcium carbonate, the shell is at least partially permeable to the fluid substance, in particular to the blowing agent. This is preferably achieved by leaving at least 0.1%, more preferably at least 0.5%, in particular 1.0% to 5% of the core surface uncoated with calcium salt, preferably not with calcium carbonate, in particular not with precipitated calcium carbonate.This effect is preferably enhanced by the gaps between individual calcium salt particles, preferably between the individual calcium carbonate particles, in particular between the individual precipitated calcium carbonate particles, which are preferably present and lead to the formation of corresponding microchannels for the fluid substance, in particular for the blowing agent.

[0193] In a particularly preferred embodiment of the present invention, the composite particles are foamed in accordance with the procedure described in the publication M. Avella, S. Cosco, ML Di Lorenzo, E. Di Pace, ME Errico, "Influence of CaCO3 Nanoparticles Shape on Thermal and Crystallization Behavior of Isotactic Polypropylene based Nanocomposites," Journal of Thermal Analysis and Calorimetry, Vol. 80 (2005), pp. 131-136. The composite particles according to the invention, which preferably comprise at least one resorbable polymer, preferably at least one resorbable polyester, in particular polylactic acid, are preferably gassed with CO2, preferably under high pressure, expediently at room temperature. The CO2 is absorbed by the polymer, and its glass transition temperature is preferably lowered. Upon pressure reduction, the composite particles foam up and preferably flow precisely out of the mold, preferably a Teflon mold.This method thus makes it possible in particular to introduce thermolabile substances, especially antibiotics and osteoinductive proteins.

[0194] The present invention will be further illustrated by several examples below, without this being intended to limit the inventive concept. characterization

[0195] The properties of the microstructured composite particle particles were determined as follows. electron microscope

[0196] Scanning electron microscopy images were acquired using a high-voltage electron microscope (Zeiss, DSM 962) at 15 kV. The samples were sprayed with a gold-palladium coating. Thermogravimetry (TGA)

[0197] Thermogravimetry was performed using a PerkinElmer STA 6000 under nitrogen (nitrogen flow rate: 20 ml / min) in the range of 40°C to 1000°C at a heating rate of 10°C / min. Example 1

[0198] Microstructured composite particles of amorphous calcium carbonate and an amorphous polylactic acid (PLA) were produced using the NHS-0 apparatus, based on the method described in JP 62083029 A. The apparatus was cooled with water at 12°C. A polylactic acid granule (mean particle size 3 mm) was used as the parent particle, and amorphous calcium carbonate powder (DSACC; mean particle size 1 µm) was used as the baby particles.

[0199] 16 g of polylactic acid granules were mixed with 4 g of CaCO₃ powder and fed into the machine at 5,000 rpm. The rotor speed was set to 16,000 rpm (100 m / s), and the added materials were processed for 1 minute. This procedure was repeated with the same material quantities and machine settings. A total of 38 g of structured composite particles were obtained.

[0200] SEM analysis showed that the PLA surface is largely covered with the spherical DSACC particles (see Fig. 1a, 1b, 1c ). Example 2

[0201] Microstructured composite particles consisting of calcium carbonate spheres (spherulites; SPH) and an amorphous polylactide (PLA) were fabricated using NHS-0 as described in Example 1. The same polylactide granules as described in Example 1 were used as the parent particles, and calcium carbonate spheres (spherulites) with a mean particle diameter of 7 µm were used as the baby particles.

[0202] 16 g of polylactic acid granules were mixed with 4 g of CaCO₃ powder and fed into the machine at 5,000 rpm. The rotor speed was set to 16,000 rpm (100 m / s), and the added materials were processed for 1 minute. A total of 5 repetitions were performed with the same material quantities and machine settings. A total of 85 g of structured composite particles were obtained.

[0203] The SEM analysis of the recovered structured composite particles is shown in the following SEM images. The PLA surface is only partially covered with the calcium carbonate spheres (spherulites) (see Fig. 2a, 2b ). Example 3

[0204] Microstructured composite particles consisting of a calcium carbonate with mixed particle shape (scalenohedra and needles; Schaefer Precarb® < 400) and a fine powder based on polyamide-12 (PA12) were produced using NHS-1. Cooling was achieved with water at 12°C. PA12 (mean particle size 50 µm) was used as the parent particle, and Schaefer Precarb® < 400 calcium carbonate (mean particle size 0.7 µm) was used as the baby particles.

[0205] 85 g of PA12 powder were mixed with 15 g of Schaefer Precarb® < 400 CaCO3 powder and fed into the unit at a rotor speed of 4,000 rpm (50 m / s). The added materials were processed for 1 minute. A total of 8 repetitions were carried out with the same material quantities and machine settings. Approximately 760 g of structured composite particles were obtained.

[0206] The SEM analysis of the obtained structured composite particles is in Fig. 3a, 3b depicted.

[0207] The CaCO3 content determined by thermogravimetry was 14.4% PCC.

[0208] The particle size distribution of the obtained structured composite particles was determined using laser diffraction (Sympatec, Helos) (d 50 = 48 µm). Example 4 (not according to the invention)

[0209] Microstructured composite particles consisting of a calcium carbonate with mixed particle shape (scalenohedra and needles; Schaefer Precarb® < 400) and a fine powder based on polyamide-12 (PA12) were produced using NHS-1. Cooling was achieved with water at 12°C. PA12 (mean particle size 50 µm) was used as the parent particle, and Schaefer Precarb® < 400 calcium carbonate (mean particle size 0.7 µm) was used as the baby particles.

[0210] 85 g of PA12 powder were mixed with 15 g of Schaefer Precarb® < 400 CaCO3 powder and fed into the unit at a rotor speed of 8,000 rpm (100 m / s). The added materials were processed for 3 minutes. Two repetitions were carried out with the same material quantities and machine settings. Approximately 196 g of structured composite particles were obtained in total.

[0211] The SEM analysis of the obtained structured composite particles is in Fig. 4a , 4b depicted.

[0212] The CaCO3 content determined by thermogravimetry was 14.1% PCC.

[0213] The particle size distribution of the obtained structured composite particles was determined using laser diffraction (Sympatec, Helos) (d 50 = 51 µm).

Claims

1. Microstructured composite particles obtainable by a process comprising combining large particles with small particles, wherein - the large particles have an average particle diameter in the range from 0.1 µm to 10 mm, - the average particle diameter of the small particles is not more than 1 / 10 of the average particle diameter of the large particles, - the large particles comprise at least one polymer, - the small particles comprise at least one calcium salt, - the small particles form an arrangement on the surface of the large particles and / or an inhomogeneous distribution within the large particles, wherein the large particles comprise at leat one resorbable polyester having an average mean of the molecular weight within the range of from 500 g / mol to 1,000,000 g / mol.

2. The composite particles according to claim 1, wherein the calcium salt comprises calcium carbonate.

3. The composite particles according to one or more of the preceding claims, wherein the calcium salt has an aspect ratio below 5.

4. The composite particles according to claim 2, wherein the calcium salt comprises precipitated calcium carbonate.

5. The composite particles according to one or more of the preceding claims, wherein the calcium salt comprises sphere-shaped calcium carbonate.

6. The composite particles according to one or more of the preceding claims, wherein the calcium carbonate comprises stabilized particles of calcium carbonate, wherein the particles of calcium carbonate comprise at least one substance having a molar mass above 100 g / mol and satisfying the formula R-Xn, where the radical R represents a radical comprising at least one carbon atom, the radical X represents a group comprising at least one oxygen atom and also at least one carbon atom, sulfur atom, phosphorus atom and / or nitrogen atom, and n represents a preferably whole number in the range from 1 to 20.

7. The composite particles according to one or more of the preceding claims, wherein the large particles comprise poly-D-, poly-L- and / or poly-D,L-lactic acid.

8. The composite particles according to one or more of the preceding claims, wherein the small particles comprise at least one calcium phosphate.

9. The composite particles according to claim 8, wherein the small particles comprise Ca3(PO4)2, CaHPO4, Ca(H2PO4), and / or Ca5(PO4)3(OH).

10. The composite particles according to one or more of the preceding claims, wherein the composite particles comprise a core and a sheath, wherein the core has an average diameter in the range from 0.5 µm to 2.0 mm and the sheath has an average thickness of not more than 20%, based on the core diameter.

11. The composite particles according to one or more of the preceding claims, wherein the weight fraction of calcium salt, based on the overall weight of the composite particles, is not less than 0.1 wt%.

12. Use of composite particles according to one or more of the preceding claims as an additive, especially as a polymer additive, as an adjuvant or as a starting material for the production of structural components, for applications in biomedical engineering and / or in microtechnology and / or for the production of foamed articles.