EP3953298A1 - Hydroxyapatite powder and method for producing same - Google Patents
Hydroxyapatite powder and method for producing sameInfo
- Publication number
- EP3953298A1 EP3953298A1 EP20716742.0A EP20716742A EP3953298A1 EP 3953298 A1 EP3953298 A1 EP 3953298A1 EP 20716742 A EP20716742 A EP 20716742A EP 3953298 A1 EP3953298 A1 EP 3953298A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- hydroxyapatite
- particles
- phosphoric acid
- powder
- primary particles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 74
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims abstract description 71
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 67
- 239000011164 primary particle Substances 0.000 claims abstract description 33
- 239000000843 powder Substances 0.000 claims abstract description 28
- 235000013305 food Nutrition 0.000 claims abstract description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 67
- 239000002245 particle Substances 0.000 claims description 45
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 33
- 230000008569 process Effects 0.000 claims description 30
- 239000000920 calcium hydroxide Substances 0.000 claims description 25
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 25
- 239000000463 material Substances 0.000 claims description 21
- 239000000725 suspension Substances 0.000 claims description 16
- 239000011575 calcium Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 10
- 239000011163 secondary particle Substances 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 8
- 239000012628 flowing agent Substances 0.000 claims description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 6
- 239000000919 ceramic Substances 0.000 claims description 3
- 230000002950 deficient Effects 0.000 claims description 3
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000004033 plastic Substances 0.000 claims description 2
- 229920003023 plastic Polymers 0.000 claims description 2
- 229940034610 toothpaste Drugs 0.000 claims description 2
- 239000000606 toothpaste Substances 0.000 claims description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 27
- 238000001556 precipitation Methods 0.000 description 10
- 239000002086 nanomaterial Substances 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 235000019700 dicalcium phosphate Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 235000014156 coffee whiteners Nutrition 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000005245 sintering Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000004438 BET method Methods 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000010459 dolomite Substances 0.000 description 1
- 229910000514 dolomite Inorganic materials 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 238000000177 wavelength dispersive X-ray spectroscopy Methods 0.000 description 1
- 238000004876 x-ray fluorescence Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/322—Preparation by neutralisation of orthophosphoric acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/015—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B14/00—Use of inorganic materials as fillers, e.g. pigments, for mortars, concrete or artificial stone; Treatment of inorganic materials specially adapted to enhance their filling properties in mortars, concrete or artificial stone
- C04B14/02—Granular materials, e.g. microballoons
- C04B14/36—Inorganic materials not provided for in groups C04B14/022 and C04B14/04 - C04B14/34
- C04B14/366—Phosphates, e.g. apatite
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/32—Phosphorus-containing compounds
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16D—COUPLINGS FOR TRANSMITTING ROTATION; CLUTCHES; BRAKES
- F16D69/00—Friction linings; Attachment thereof; Selection of coacting friction substances or surfaces
- F16D69/02—Composition of linings ; Methods of manufacturing
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/50—Agglomerated particles
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/54—Particles characterised by their aspect ratio, i.e. the ratio of sizes in the longest to the shortest dimension
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/61—Micrometer sized, i.e. from 1-100 micrometer
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/62—Submicrometer sized, i.e. from 0.1-1 micrometer
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2006/00—Physical properties of inorganic compounds
- C01P2006/11—Powder tap density
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2006/00—Physical properties of inorganic compounds
- C01P2006/12—Surface area
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/32—Phosphorus-containing compounds
- C08K2003/321—Phosphates
- C08K2003/325—Calcium, strontium or barium phosphate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K2201/00—Specific properties of additives
- C08K2201/002—Physical properties
- C08K2201/005—Additives being defined by their particle size in general
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K2201/00—Specific properties of additives
- C08K2201/002—Physical properties
- C08K2201/006—Additives being defined by their surface area
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16D—COUPLINGS FOR TRANSMITTING ROTATION; CLUTCHES; BRAKES
- F16D2200/00—Materials; Production methods therefor
- F16D2200/0034—Materials; Production methods therefor non-metallic
Definitions
- the present invention relates to a hydroxyapatite powder which consists of particles with special properties, in particular relating to the particle size.
- the present invention also relates to a method for producing such a hydroxyapatite powder, in which milk of lime is reacted with phosphoric acid to form hydroxyapatite.
- the present invention relates to the use of the hydroxyapatite powder according to the invention in various fields of application.
- Hydroxyapatite forms in aqueous systems at temperatures of up to 100 ° C in the form of primary particles in which at least one spatial axis is ⁇ 0.10 ⁇ m in dimension.
- primary particles can be obtained that have edge lengths in all spatial directions that are> 0.1 ⁇ m.
- these primary crystals have a columnar shape and result in a powder with a relatively large specific surface area in the region of around 70 m 2 / g.
- the bulk densities of these materials are typically in the range of 200-350 g / l.
- hydroxyapatite is mostly produced by reacting milk of lime with phosphoric acid, and this results in very fine, needle-shaped primary particles that can agglomerate into secondary particles in the micrometer range.
- processes are also described in which the precipitation is carried out in an autoclave under elevated pressure at temperatures above 100 ° C. (e.g. EP 1 401 762).
- hydroxyapatite can also be obtained by precipitation of aqueous solutions of water-soluble calcium salts in the presence of water-soluble phosphate or fluoride salts.
- water-soluble surfactants, water-soluble polymeric protective colloids or chelating agents such as. B. EDTA (cf. EP 1 139 995 and US 7,998,219 B2).
- nanomaterial is a material that contains particles in an unbound state, as an aggregate or as an agglomerate, and in which at least 50% of the particles in the number size distribution have one or more external dimensions in the range of 1-100 nm.
- nanomaterials have recently been viewed more and more critically, especially in food technology, due to their ability to penetrate biomembrane, there is a need for materials that are not nanomaterials in the sense defined above, especially for hydroxyapatite powders that are to be used in the food sector represent. In particular, there is a need for a method with which a hydroxyapatite powder which has no nano-properties can be obtained in a targeted and reliable manner.
- the particle size in one dimension is clearly in the nanometer range.
- the smallest dimension of the needles obtained at 40 ° C is 25 nm and the particle diameter of the spherical particles obtained from 100 ° C is 50 nm.
- a hydroxylapatite powder that does not fall under the above definition of “nanomaterials” and can therefore also be used in the food sector without the concerns associated with the use of nanomaterials.
- the object of the present invention is achieved in that a hydroxyapatite powder is provided which is composed of primary particles, the median of the primary particles from which the powder is formed being> 0.10 ⁇ m and the aspect ratio of the primary particles ⁇ 5 is, the specific surface of the hydroxyapatite powder is ⁇ 10 m 2 / g and the bulk density is> 550 g / l.
- hydroxyapatite powders are typically formed from primary particles, which in turn can agglomerate to form secondary particles.
- the present invention is now characterized in that the primary particles of the hydroxyapatite powder have an aspect ratio of ⁇ 5, the aspect ratio expressing the ratio of the largest average size of the particles in a first dimension to the smallest average size of the particles in a second dimension.
- the primary particles have a significantly greater compactness than is the case with needle-shaped hydroxyapatite primary particles from the prior art.
- the primary particles of the hydroxylapatite powder according to the invention preferably have an aspect ratio of ⁇ 3 or even ⁇ 2 and are therefore particularly compact. In these areas, the primary particles have a cuboid or egg-shaped to almost spherical shape.
- the aspect ratio is determined by means of optical analysis. For a portion of the powder, the largest size of the particles in a first dimension and the smallest size of the particles in a second dimension are measured under the scanning electron microscope and the statistical mean (arithmetic mean) of the respective values is compared.
- the median of the primary particles of the hydroxylapatite powder according to the invention is above 0.10 ⁇ m and is determined using dynamic light scattering and based on the number of particles.
- the median of the primary particles is> 0.1-1 pm, more preferably> 0.12 pm, particularly preferably> 0.13 pm.
- the further the median of the primary particles is from the limit value below which, according to the above definition, a nanomaterial is present, the lower the proportion of particles in this material that are below this limit, which is particularly important under the aspect of membrane permeability mentioned at the beginning small particles is particularly advantageous for food applications.
- the upper limit of the median of the primary particles is preferably ⁇ 10 pm, ⁇ 9 pm, ⁇ 8 pm, ⁇ 7 pm, ⁇ 6 pm or even ⁇ 5 pm.
- the specific surface of the hydroxyapatite powder according to the invention is ⁇ 10 m 2 / g and is determined by BET measurement using the absorption of nitrogen in accordance with DIN ISO 9277.
- the specific surface of the hydroxyapatite powder is ⁇ 8 m 2 / g and in particularly preferred embodiments ⁇ 7 m 2 / g.
- a specific surface area that is as small as possible is desired and advantageous for certain applications for the hydroxyapatite powder according to the invention. From this point of view, depending on the specific requirements placed on the material, it is desirable to have available hydroxyapatite powders that have a particularly small specific surface area.
- the bulk density of the hydroxyapatite powder is more than 550 g / l, and the bulk density is determined according to the method defined in DIN ISO 697 without compaction in a bulk weight cylinder.
- the present invention also achieves bulk densities of> 600 g / l or even> 650 g / l in certain embodiments. This is particularly advantageous when the hydroxyapatite powder according to the invention is used as a free-flowing agent mixed with powder materials which have a correspondingly high bulk density in order to improve the free-flowing properties.
- hydroxyapatite powder includes powdery materials which consist of at least 95% by weight of CasCPO ⁇ OH.
- the term includes not only such powders, the particles of which consist of 100% by weight of pure hydroxyapatite, but also powders which, for example, contain mixed crystals of hydroxyapatite with e.g. Include dolomite as long as the total amount of CasCPO ⁇ OH is at least 95% by weight of the powder.
- the hydroxyapatite powder according to the invention can also contain small amounts of
- Calcium hydrogen phosphate (CaHP0 4 ) or calcium hydrogen phosphate dihydrate (CaHP0 4 * 2 H 2 O) have as a secondary phase, as long as the total amount of Cas (P0 4 ) 3 OH is at least 90% by weight of the powder.
- Preferred hydroxyapatite powders according to the present invention consist of at least 95% by weight, at least 97% by weight, at least 98% by weight or at least 99% by weight of Ca 5 (P0 4 ) 3 OH.
- the present invention also includes hydroxyapatite powders in which a proportion of up to 10 atom% of the calcium ions in the hydroxyapatite is exchanged for foreign ions, such as magnesium, iron and zinc ions.
- the proportion of calcium ions exchanged for foreign ions is at most 5 atom%, at most 3 atom%, or only at most 1 atom%.
- the hydroxyapatite from which the powder is formed is calcium-saturated hydroxyapatite with the stoichiometric formula Ca 5 (P0 4 ) 3 OH.
- the hydroxyapatite is calcium-deficient hydroxyapatite with the formula Caio- x (P0 4 ) 6-x (HP0 4 ) x (OH) 2-x , where 0 ⁇ x ⁇ 2.
- the saturation of the hydroxyapatite is determined by means of X-ray fluorescence analysis (e.g. Malvern Panalytical, Axios, WDXRF). If the measured saturation is ⁇ 3.33, it is a calcium-deficient hydroxyapatite. From 3.33 or above it is a calcium-saturated hydroxyapatite.
- At least 90% by weight of the primary particles of the hydroxyapatite powder according to the invention are agglomerated to form secondary particles, preferably at least 95% by weight, more preferably at least 98% by weight.
- the median of the size of the secondary particles is> 1.0 pm. In certain embodiments, the median of the secondary particles is> 10.0 pm or even> 100 pm.
- the upper limit of the median of the secondary particles is ⁇ 50 mhi, ⁇ 40 mhi, ⁇ 30 min, ⁇ 20 min, ⁇ 15 min, ⁇ 10 min, ⁇ 9 miti, ⁇ 8 mhi, ⁇ 1 mhi, ⁇ 6 miti or even ⁇ 5 mhi.
- the hydroxylapatite powder according to the invention can be obtained by a process in which a reaction mixture is produced in which milk of lime is reacted with phosphoric acid to form hydroxylapatite, this process being particularly characterized in that a process cycle with the following process steps is carried out: a) providing a suspension of hydroxyapatite starting particles in water,
- the process is carried out in semi-continuous operation, the proportion of the hydroxylapatite particles separated in process step d) always being removed from the process which, in the dried state, has a median of the primary particles of> 0.10 pm, while the remaining portion is resuspended in water in process step a) in order to provide a suspension of hydroxyapatite starter particles in water.
- the process is carried out in fully continuous operation, with the proportion of hydroxylapatite particles being continuously separated off in process step d) and removed from the process cycle, which in the dried state has a median of the primary particles of> 0, 10 pm, while the remaining portion remains in the process cycle.
- the continuous separation and removal is preferably carried out with an inclined clarifier or a centrifuge (e.g. inverted centrifuge or pusher centrifuge).
- hydroxyapatite starting particles with a median of ⁇ 0.1 ⁇ m are used in method step a) and method steps a) to e) are repeated at least once in order to obtain a hydroxyapatite powder whose primary particles have a median of> 0, 10 ⁇ m and an aspect ratio of ⁇ 5, the specific surface of the hydroxyapatite powder being ⁇ 10 m 2 / g and the bulk density being> 550 g / l.
- the process is carried out in continuous operation, with a proportion of the hydroxylapatite particles separated in process step d) whose primary particles have a median of> 0.10 ⁇ m and an aspect ratio of ⁇ 5 and their specific surface area ⁇ 10 m 2 / g and whose bulk density is> 550 g / l, is removed from the process, while the remaining portion in process step a) is resuspended in water in order to then go through the repeated process steps b) to e).
- the conversion of the milk of lime with the phosphoric acid should be as uniform and controlled as possible. It is therefore crucial for the success of the present invention that the temperature in the reaction mixture is above 20 ° C and below 105 ° C.
- the milk of lime is reacted with the phosphoric acid in the reaction mixture to form hydroxyapatite at a temperature in the range from> 60 ° C and ⁇ 100 ° C or at a temperature in the range from> 80 ° C and ⁇ 100 ° C.
- the pH be in the range of 6.0-13.0.
- Calcium hydrogen phosphate (CaHPC) or calcium hydrogen phosphate dihydrate (CaHPC> 4 * 2 H2O) precipitate at a pH value of ⁇ 6.0.
- the milk of lime is reacted with the phosphoric acid in the reaction mixture to form hydroxyapatite at a pH in the range from 7.0 to 11.0, since under certain conditions above pH 11.0, more Ca (OH ) 2 can occur as a minor phase.
- the conversion to hydroxyapatite takes place at a pH in the range from 7.0 to 9.0, since, under certain conditions above pH 9.0, inclusions of Ca (OH) 2 can occur at least partially .
- the conversion of phosphoric acid and milk of lime in the reaction mixture is carried out at atmospheric pressure. If desired, however, it is also possible to work at slightly increased pressure, preferably up to an excess pressure of 1 bar.
- the particles obtained by the process according to the invention are washed with water, separated off by filtration or centrifugation and dried. How this has to be done in detail is known to the person skilled in the art and therefore does not require any further explanations.
- One of the starting materials of the process according to the invention is phosphoric acid (H 3 PO4).
- the phosphoric acid used is dilute phosphoric acid with a concentration of 5 to 25% by volume of phosphoric acid in water. Low phosphoric acid concentrations promote the growth of germs, but at the same time lead to larger volumes of the reaction mixture.
- the concentration of the phosphoric acid used is therefore in the range from 10 to 25% by volume of phosphoric acid in water or in the range from 15 to 25% by volume of phosphoric acid in water.
- the second starting material of the process according to the invention is milk of lime (suspension of Ca (OH) 2 in water).
- the oxide-based milk of lime has a concentration of 2 to 20% by weight, preferably 8 to 12% by weight.
- the milk of lime and the phosphoric acid can be added one after the other in process step b), the time interval between the addition of these two starting materials being as short as possible.
- milk of lime and phosphoric acid are preferably added to the initial charge at the same time.
- hydroxyapatite starter particles the particle size of which is characterized by a median of ⁇ 0.1 ⁇ m.
- these particles have a bulk density in the range from 200 to 350 g / l and a specific surface area in the range from 15 to 50 m 2 / g.
- primary particles of the desired size and shape are obtained through the repeated stacking of hydroxyapatite layers during process step c). This takes place in that the milk of lime added to the reaction mixture is reacted in situ with the phosphoric acid added to the reaction mixture to form hydroxyapatite.
- the repeated conversion of freshly added milk of lime and freshly added phosphoric acid takes place in process step c) both for the first time and for each repeated execution with stirring.
- the mechanical stress during stirring should be kept as low as possible. Accordingly, in certain embodiments of the method according to the invention, the maximum speed of the section of the stirrer outermost in the plane of rotation is ⁇ 2 m / s, more preferably ⁇ 1 m / s and particularly preferably ⁇ 0.5 m / s. If the mechanical stress on the reaction mixture is too high, new crystallization nuclei would arise, which would hinder the process according to the invention of layering further hydroxylapatite layers on existing particles.
- the repeated conversion of freshly added milk of lime and freshly added phosphoric acid takes place in process step c) both for the first time and for each repeated execution, preferably over a certain period of time.
- the hydroxyapatite powder provided by the present invention can be put to various uses.
- the hydroxylapatite powder according to the invention is used for fortifying foods, such as. B. milk or cheese, used with calcium.
- the hydroxyapatite powder according to the invention is used as a free-flowing agent in foodstuffs to improve their flow properties. Combined use is also contemplated, i.e. both as a free-flowing agent and for calcium enrichment.
- the hydroxyapatite powder according to the invention is used as a filler for plastics and ceramics or as an abrasive in toothpaste or as a hard material in brake linings.
- Examples 1.1-1.4 describe different manufacturing processes for hydroxylapatite powder (HAP).
- aqueous suspension of HAP material from 1.1
- a solids content of 13% is heated to 90 ° C. in a kettle; the amount of HAP initially charged is 10% of the desired target amount.
- milk of lime with a calculated content of 10% CaO and 20% phosphoric acid added while maintaining a specific pH value in the range from 7.0 to 9.0.
- the suspension is for a further 15 min. touched. 90% of the suspension is then filtered off, washed and dried.
- the attempts at simultaneous precipitation were repeated seven times (V2-V8) after the first precipitation (V1), the remaining 10% serving as a template for the next precipitation by this method.
- Material from 1.1 is sintered together by thermal treatment.
- the material was heated in Alusint crucibles to 300, 500 and 900 ° C for 12 h each (V1 - V3).
- X-ray diffraction Bruker D8 Advance, CuKa, 40kV; 40.0 mA; l 1, 5406 ⁇ ; LynxEye detector
- Particle size distributions through dynamic light scattering (“Horiba”) based on both volume and particle size, specific surface area according to the BET method through N2 absorption (DIN ISO 9277).
- Table 1 Overview of the analysis values from experiments 1.1-1.2.
- Table 2 Overview of the analysis values from experiments 1.3-1.4.
- test results show that the addition of hydroxyapatite powder according to the invention gives the various coffee whiteners good flow properties.
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Abstract
The aim of the invention is to produce a hydroxyapatite which can be used in the food sector without reservation. The invention provides a hydroxyapatite powder which is composed of primary particles, wherein the median of the primary particles from which the powder is made is > 0.10 |jm, the specific surface area of the hydroxyapatite powder is :g10 m2/g, and the bulk density is > 550 g/l. The invention additionally relates to a method with which such a hydroxyapatite can be obtained.
Description
Hydroxylapatit-Pulver und Verfahren zu dessen Herstellung Hydroxyapatite powder and process for its manufacture
Die vorliegende Erfindung betrifft ein Hydroxylapatit-Pulver, das aus Partikeln mit besonderen Eigenschaften besteht, die insbesondere die Partikelgröße betreffen. Des Weiteren betrifft die vorliegende Erfindung ein Verfahren zur Herstellung eines solchen Hydroxylapatit-Pulvers, bei dem Kalkmilch mit Phosphorsäure zu Hydroxylapatit umgesetzt wird. Darüber hinaus betrifft die vorliegende Erfindung die Verwendung des erfindungsgemäßen Hydroxylapatit-Pulvers auf verschiedenen Anwendungsgebieten. The present invention relates to a hydroxyapatite powder which consists of particles with special properties, in particular relating to the particle size. The present invention also relates to a method for producing such a hydroxyapatite powder, in which milk of lime is reacted with phosphoric acid to form hydroxyapatite. In addition, the present invention relates to the use of the hydroxyapatite powder according to the invention in various fields of application.
Hydroxylapatit bildet sich in wässrigen Systemen bei Temperaturen bis 100 °C in Form von Primärpartikeln, bei denen wenigstens eine räumliche Achse in ihrer Dimension < 0,10 pm ist. Bei höheren Temperaturen (> 100 °C), z. B. durch Hydrothermalsynthese (150-250 °C) oder Fluxsynthese (400-700 °C) können zwar auch Primärpartikel erhalten werden, die in allen Raumrichtungen Kantenlängen aufweisen, die > 0, 10 pm sind. Allerdings weisen diese Primärkristalle eine säulenartige Gestalt auf und resultieren in einem Pulver relativ großer spezifischer Oberfläche im Bereich um etwa 70 m2/g. Die Schüttdichten dieser Materialein liegen typischerweise im Bereich von 200-350 g/l. Hydroxyapatite forms in aqueous systems at temperatures of up to 100 ° C in the form of primary particles in which at least one spatial axis is <0.10 μm in dimension. At higher temperatures (> 100 ° C), e.g. B. by hydrothermal synthesis (150-250 ° C) or flux synthesis (400-700 ° C), primary particles can be obtained that have edge lengths in all spatial directions that are> 0.1 μm. However, these primary crystals have a columnar shape and result in a powder with a relatively large specific surface area in the region of around 70 m 2 / g. The bulk densities of these materials are typically in the range of 200-350 g / l.
Großtechnisch erfolgt die Herstellung von Hydroxylapatit zumeist durch Umsetzung von Kalkmilch mit Phosphorsäure, und hierbei entstehen sehr feine, nadelförmige Primärpartikel, die zu Sekundärpartikeln im Mikrometer-Bereich agglomerieren können. Teilweise werden auch Verfahren beschrieben, bei denen die Fällung in einem Autoklaven unter erhöhtem Druck bei Temperaturen von oberhalb 100 °C durchgeführt wird (z. B. EP 1 401 762). Alternativ kann Hydroxylapatit auch durch Fällung von wässrigen Lösungen wasserlöslicher Calciumsalze in Gegenwart wasserlöslicher Phosphat- oder Fluoridsalze erhalten werden. Teilweise erfolgt hierbei der Zusatz von wasserlöslichen Tensiden, wasserlöslichen polymeren Schutzkolloiden oder von Chelatbildnern, wie z. B. EDTA (vgl. EP 1 139 995 und US 7,998,219 B2). On a large scale, hydroxyapatite is mostly produced by reacting milk of lime with phosphoric acid, and this results in very fine, needle-shaped primary particles that can agglomerate into secondary particles in the micrometer range. In some cases, processes are also described in which the precipitation is carried out in an autoclave under elevated pressure at temperatures above 100 ° C. (e.g. EP 1 401 762). Alternatively, hydroxyapatite can also be obtained by precipitation of aqueous solutions of water-soluble calcium salts in the presence of water-soluble phosphate or fluoride salts. In some cases, water-soluble surfactants, water-soluble polymeric protective colloids or chelating agents, such as. B. EDTA (cf. EP 1 139 995 and US 7,998,219 B2).
Aufgrund der Struktur und Größe der Primärpartikel der nach dem genannten Verfahren erhaltenen Hydroxylapatit-Materialien fallen solche Produkte unter die Definition des Begriffes "Nanomaterial", wie es von der Kommission der Europäischen Union am 18. Oktober 201 1 (2011/696/EU) definiert wurde. Demnach ist ein "Nanomaterial" ein Material, das Partikel in ungebundenem Zustand, als Aggregat oder als Agglomerat enthält, und bei dem mindestens
50 % der Partikel in der Anzahlgrößenverteilung ein oder mehrere Außenmaße im Bereich von 1-100 nm haben. Due to the structure and size of the primary particles of the hydroxyapatite materials obtained by the process mentioned, such products fall under the definition of the term "nanomaterial" as defined by the Commission of the European Union on October 18, 2011 (2011/696 / EU) has been. Accordingly, a “nanomaterial” is a material that contains particles in an unbound state, as an aggregate or as an agglomerate, and in which at least 50% of the particles in the number size distribution have one or more external dimensions in the range of 1-100 nm.
Da "Nanomaterialien" aufgrund ihrer Fähigkeit Biomembranen zu penetrieren vor allem in der Lebensmitteltechnologie in letzter Zeit zunehmend kritisch gesehen werden, besteht insbesondere für Hydroxylapatit-Pulver, die im Lebensmittelbereich zur Anwendung kommen sollen, ein Bedarf nach Materialien, die keine Nanomaterialien im oben definierten Sinne darstellen. Insbesondere besteht Bedarf nach einem Verfahren, mit dem man gezielt und zuverlässig ein Hydroxylapatit-Pulver erhalten kann, das keine Nanoeigenschaften aufweist. Since "nanomaterials" have recently been viewed more and more critically, especially in food technology, due to their ability to penetrate biomembrane, there is a need for materials that are not nanomaterials in the sense defined above, especially for hydroxyapatite powders that are to be used in the food sector represent. In particular, there is a need for a method with which a hydroxyapatite powder which has no nano-properties can be obtained in a targeted and reliable manner.
Eine Möglichkeit, wie solche Materialien theoretisch erhalten werden könnten, stellt das Zusammensintern von herkömmlichen Hydroxylapatit-Pulvern bei Temperaturen im Bereich von 300-900 °C dar. Die auf diese Weise erhältlichen Materialien weisen jedoch sehr große spezifische Oberflächen von teilweise deutlich mehr als 10,0 m2/g auf, was für solche Anwendungen nachteilig ist, bei denen die mit einer großen spezifischen Oberfläche verbundenen Absorptionseigenschaften unerwünscht sind. One possibility how such materials could theoretically be obtained is the sintering together of conventional hydroxyapatite powders at temperatures in the range of 300-900 ° C. The materials obtainable in this way, however, have very large specific surface areas, sometimes significantly more than 10, 0 m 2 / g, which is disadvantageous for those applications in which the absorption properties associated with a large specific surface are undesirable.
Ein weiterer Ansatz könnte sein, die Bildungskinetik von Hydroxylapatit-Pulvern durch Variationen der Temperatur bei der Ausfällung zu beeinflussen. Kumar, R., et al., beschreiben in ihrer Veröffentlichung "Temperature Driven Morphological Changes of Chemically Precipi- tated Hydroxyapatite Nanoparticles" (Langmuir 2004, 20, 5196-5200) den Einfluss der Temperatur auf die Morphologie von gefällten Hydroxylapatit-Partikeln. Insbesondere wird in dieser Veröffentlichung festgestellt, dass bei einer Temperatur von etwa 40 °C Partikel erhalten werden, die nadelförmig sind. Bei 80 °C wandelt sich die Morphologie der erhaltenen Partikel in eine eher pyramidale Form mit einem geringeren Aspektverhältnis und ab 100 °C wird die Partikelmorphologie sphärisch. In allen drei Fällen liegt die Partikelgröße jedenfalls in einer Dimension jedoch deutlich im Nanometerbereich. So beträgt beispielsweise die geringste Ausdehnung der bei 40 °C erhaltenen Nadeln 25 nm und der Partikeldurchmesser der ab 100 °C erhaltenen sphärischen Partikel beträgt 50 nm. Somit fallen all diese Hydroxylapatitprodukte unter die obige Definition von "Nanomaterialien". Another approach could be to influence the kinetics of formation of hydroxyapatite powders by varying the temperature during the precipitation. Kumar, R., et al., In their publication "Temperature Driven Morphological Changes of Chemically Precipitated Hydroxyapatite Nanoparticles" (Langmuir 2004, 20, 5196-5200) describe the influence of temperature on the morphology of precipitated hydroxyapatite particles. In particular, this publication states that at a temperature of approximately 40 ° C., particles are obtained which are needle-shaped. At 80 ° C the morphology of the particles obtained changes into a more pyramidal shape with a lower aspect ratio and from 100 ° C the particle morphology becomes spherical. In all three cases, however, the particle size in one dimension is clearly in the nanometer range. For example, the smallest dimension of the needles obtained at 40 ° C is 25 nm and the particle diameter of the spherical particles obtained from 100 ° C is 50 nm. Thus, all these hydroxyapatite products fall under the above definition of "nanomaterials".
Vor diesem Hintergrund ist es die Aufgabe der vorliegenden Erfindung ein Hydroxylapatit- Pulver bereitzustellen, das nicht unter die obige Definition von "Nanomaterialien" fällt und somit ohne die mit der Verwendung von Nanomaterialien verbundenen Bedenken auch im Lebensmittelbereich eingesetzt werden kann.
Die Aufgabe der vorliegenden Erfindung wird dadurch gelöst, dass ein Hydroxylapatit-Pulver bereitgestellt wird, das aus Primärpartikeln zusammengesetzt ist, wobei der Median der Primärpartikel, aus dem das Pulver gebildet ist, bei > 0,10 pm liegt und das Aspektverhältnis der Primärpartikel < 5 beträgt, wobei die spezifische Oberfläche des Hydroxylapatit-Pulvers < 10 m2/g ist und die Schüttdichte > 550 g/l beträgt. Against this background, it is the object of the present invention to provide a hydroxylapatite powder that does not fall under the above definition of “nanomaterials” and can therefore also be used in the food sector without the concerns associated with the use of nanomaterials. The object of the present invention is achieved in that a hydroxyapatite powder is provided which is composed of primary particles, the median of the primary particles from which the powder is formed being> 0.10 μm and the aspect ratio of the primary particles <5 is, the specific surface of the hydroxyapatite powder is <10 m 2 / g and the bulk density is> 550 g / l.
Wie eingangs bereits erwähnt wurde, werden Hydroxylapatit-Pulver typischerweise von Primärpartikeln gebildet, die wiederum zu Sekundärpartikeln agglomerieren können. Die vorliegende Erfindung zeichnet sich nun dadurch aus, dass die Primärpartikel des Hydroxylapatit- Pulvers ein Aspektverhältnis von < 5 aufweisen, wobei das Aspektverhältnis das Verhältnis der größten durchschnittlichen Ausdehnung der Partikel in einer ersten Dimension zur kleinsten durchschnittlichen Ausdehnung der Partikel in einer zweiten Dimension ausdrückt. As already mentioned at the beginning, hydroxyapatite powders are typically formed from primary particles, which in turn can agglomerate to form secondary particles. The present invention is now characterized in that the primary particles of the hydroxyapatite powder have an aspect ratio of <5, the aspect ratio expressing the ratio of the largest average size of the particles in a first dimension to the smallest average size of the particles in a second dimension.
Durch das erfindungsgemäß erreichte Aspektverhältnis von < 5 weisen die Primärpartikel eine deutlich höhere Kompaktheit auf, als dies bei nadelförmigen Hydroxylapatit-Primärpartikeln aus dem Stand der Technik der Fall ist. Vorzugsweise weisen die Primärpartikel des erfindungsgemäßen Hydroxylapatit-Pulvers ein Aspektverhältnis von < 3 oder gar < 2 auf und haben damit eine besonders große Kompaktheit. In diesen Bereichen sind die Primärpartikel von kuboider bzw. eiförmiger bis nahezu sphärischer Gestalt. As a result of the aspect ratio of <5 achieved according to the invention, the primary particles have a significantly greater compactness than is the case with needle-shaped hydroxyapatite primary particles from the prior art. The primary particles of the hydroxylapatite powder according to the invention preferably have an aspect ratio of <3 or even <2 and are therefore particularly compact. In these areas, the primary particles have a cuboid or egg-shaped to almost spherical shape.
Die Bestimmung des Aspektverhältnisses erfolgt mittels optischer Analyse. Hierbei werden für einen Anteil des Pulvers unter dem Rasterelektronenmikroskop die größte Ausdehnung der Partikel in einer ersten Dimension und die kleinste Ausdehnung der Partikel in einer zweiten Dimension gemessen und das statistische Mittel (arithmetischer Mittelwert) der jeweiligen Werte ins Verhältnis gesetzt. The aspect ratio is determined by means of optical analysis. For a portion of the powder, the largest size of the particles in a first dimension and the smallest size of the particles in a second dimension are measured under the scanning electron microscope and the statistical mean (arithmetic mean) of the respective values is compared.
Der Median der Primärpartikel des erfindungsgemäßen Hydroxylapatit-Pulvers liegt oberhalb von 0,10 pm und wird anhand dynamischer Lichtstreuung und basierend auf der Anzahl der Partikel bestimmt. Bei bevorzugten Ausführungsformen der Erfindung ist der Median der Primärpartikel > 0,1 1 pm, noch bevorzugter > 0,12 pm, besonders bevorzugt > 0,13 pm. Je weiter der Median der Primärpartikel von dem Grenzwert entfernt liegt, unterhalb dessen nach der obigen Definition ein Nanomaterial vorliegt, desto geringer ist der Anteil an Partikeln in diesem Material, die unterhalb dieser Grenze liegen, was vor allem unter dem eingangs erwähnten Aspekt der Membrangängigkeit solch kleiner Partikel insbesondere für Lebensmittelanwendungen von Vorteil ist. The median of the primary particles of the hydroxylapatite powder according to the invention is above 0.10 μm and is determined using dynamic light scattering and based on the number of particles. In preferred embodiments of the invention, the median of the primary particles is> 0.1-1 pm, more preferably> 0.12 pm, particularly preferably> 0.13 pm. The further the median of the primary particles is from the limit value below which, according to the above definition, a nanomaterial is present, the lower the proportion of particles in this material that are below this limit, which is particularly important under the aspect of membrane permeability mentioned at the beginning small particles is particularly advantageous for food applications.
Die Obergrenze des Medians der Primärpartikel ist vorzugsweise < 10 pm, < 9 pm, < 8 pm, < 7 pm, < 6 pm oder gar < 5 pm.
Die spezifische Oberfläche des erfindungsgemäßen Hydroxylapatit-Pulvers ist < 10 m2/g und wird durch BET-Messung anhand der Absorption von Stickstoff nach DIN ISO 9277 bestimmt. Bei bevorzugten Ausführungsformen der Erfindung ist die spezifische Oberfläche des Hydroxylapatit-Pulvers < 8 m2/g und bei besonders bevorzugten Ausführungsformen < 7 m2/g. Wie eingangs bereits erwähnt wurde, ist eine möglichst kleine spezifische Oberfläche bei bestimmten Anwendungen für das erfindungsgemäße Hydroxylapatit-Pulver gewünscht und von Vorteil. Unter diesem Gesichtspunkt ist es je nach spezifischer Anforderung an das Material erstrebenswert Hydroxylapatit-Pulver verfügbar zu haben, die eine besonders geringe spezifische Oberfläche aufweisen. The upper limit of the median of the primary particles is preferably <10 pm, <9 pm, <8 pm, <7 pm, <6 pm or even <5 pm. The specific surface of the hydroxyapatite powder according to the invention is <10 m 2 / g and is determined by BET measurement using the absorption of nitrogen in accordance with DIN ISO 9277. In preferred embodiments of the invention, the specific surface of the hydroxyapatite powder is <8 m 2 / g and in particularly preferred embodiments <7 m 2 / g. As already mentioned at the beginning, a specific surface area that is as small as possible is desired and advantageous for certain applications for the hydroxyapatite powder according to the invention. From this point of view, depending on the specific requirements placed on the material, it is desirable to have available hydroxyapatite powders that have a particularly small specific surface area.
Erfindungsgemäß beträgt die Schüttdichte des Hydroxylapatit-Pulvers mehr als 550 g/l, und die Bestimmung der Schüttdichte erfolgt nach dem in der DIN ISO 697 definierten Verfahren ohne Verdichtung in einem Schüttgewichtszylinder. Je nach Anforderung werden mit der vorliegenden Erfindung bei bestimmten Ausführungsformen auch Schüttdichten von > 600 g/l o- der gar > 650 g/l erreicht. Dies ist insbesondere dann von Vorteil, wenn das erfindungsgemäße Hydroxylapatit-Pulver als Freifließmittel im Gemisch mit Pulvermaterialien, die ein entsprechend hohes Schüttgewicht aufweisen, zum Einsatz kommt, um die Freifließfähigkeit zu verbessern. Je näher das Schüttgewicht des Freifließmittels beim Schüttgewicht des damit zu mischenden Pulvermaterials liegt, desto geringer neigt das entsprechende Produkt zur Entmischung. Beispiele hierfür sind z.B. keramische Mischungen oder Mischungen von unterschiedlichen Metallsalzen zur Mineralstoffanreicherung. According to the invention, the bulk density of the hydroxyapatite powder is more than 550 g / l, and the bulk density is determined according to the method defined in DIN ISO 697 without compaction in a bulk weight cylinder. Depending on the requirements, the present invention also achieves bulk densities of> 600 g / l or even> 650 g / l in certain embodiments. This is particularly advantageous when the hydroxyapatite powder according to the invention is used as a free-flowing agent mixed with powder materials which have a correspondingly high bulk density in order to improve the free-flowing properties. The closer the bulk density of the free-flowing agent is to the bulk density of the powder material to be mixed with it, the less the corresponding product tends to separate. Examples are e.g. ceramic mixtures or mixtures of different metal salts for mineral enrichment.
Unter den Begriff Hydroxylapatit-Pulver fallen nach der vorliegenden Erfindung pulverförmige Materialien die zu wenigstens 95 Gew.-% aus CasCPO^OH bestehen. Somit umfasst der Begriff nicht nur solche Pulver, dessen Partikel zu 100 Gew.-% aus reinem Hydroxylapatit bestehen, sondern auch Pulver, die beispielsweise einen Anteil an Mischkristallen von Hydroxylapatit mit z.B. Dolomit umfassen, solange der Gesamtanteil an CasCPO^OH wenigstens 95 Gew.-% des Pulvers ausmacht. According to the present invention, the term hydroxyapatite powder includes powdery materials which consist of at least 95% by weight of CasCPO ^ OH. Thus, the term includes not only such powders, the particles of which consist of 100% by weight of pure hydroxyapatite, but also powders which, for example, contain mixed crystals of hydroxyapatite with e.g. Include dolomite as long as the total amount of CasCPO ^ OH is at least 95% by weight of the powder.
Je nach den konkreten Bedingungen, unter denen das erfindungsgemäße Hydroxylapatit- Pulver erzeugt wurde (z.B. pH < 7), kann es auch geringe Anteile anDepending on the specific conditions under which the hydroxyapatite powder according to the invention was produced (e.g. pH <7), it can also contain small amounts of
Calciumhydrogenphosphat (CaHP04) oder Calciumhydrogenphosphatdihydrat (CaHP04 *2 H2O) als Nebenphase aufweisen, solange der Gesamtanteil an Cas(P04)30H wenigstens 90 Gew.-% des Pulvers ausmacht. Dies entspricht den etablierten FCC- (Food Chemicals Codex) und Pharma-Richtlinien, wonach eine Reinheit von mindestens 90% verlangt wird, damit ein Material als Hydroxylapatit bezeichnet werden darf.
Bevorzugte Hydroxylapatit-Pulver nach der vorliegenden Erfindung bestehen zu wenigstens 95 Gew.-%, zu wenigstens 97 Gew.-%, zu wenigstens 98 Gew.-% oder zu wenigstens 99 Gew.-% aus Ca5(P04)30H. Calcium hydrogen phosphate (CaHP0 4 ) or calcium hydrogen phosphate dihydrate (CaHP0 4 * 2 H 2 O) have as a secondary phase, as long as the total amount of Cas (P0 4 ) 3 OH is at least 90% by weight of the powder. This corresponds to the established FCC (Food Chemicals Codex) and pharmaceutical guidelines, according to which a purity of at least 90% is required so that a material can be designated as hydroxyapatite. Preferred hydroxyapatite powders according to the present invention consist of at least 95% by weight, at least 97% by weight, at least 98% by weight or at least 99% by weight of Ca 5 (P0 4 ) 3 OH.
Umfasst sind von der vorliegenden Erfindung außerdem Hydroxylapatit-Pulver, bei denen ein Anteil von bis zu 10 Atom% der Calcium-Ionen im Hydroxylapatit durch Fremdionen, wie z.B. Magnesium-, Eisen- und Zinkionen, ausgetauscht ist. Bei bevorzugten Hydroxylapatit-Pulvern nach der vorliegenden Erfindung beträgt der Anteil der Calcium-Ionen, die durch Fremdionen ausgestauscht sind, höchstens 5 Atom%, höchstens 3 Atom%, oder nur höchstens 1 Atom%. Bei bestimmten Ausführungsformen der Erfindung handelt es sich bei dem Hydroxylapatit, aus dem das Pulver gebildet wird um Calcium-gesättigtes Hydroxylapatit mit der stöchiometrischen Formel Ca5(P04)30H. The present invention also includes hydroxyapatite powders in which a proportion of up to 10 atom% of the calcium ions in the hydroxyapatite is exchanged for foreign ions, such as magnesium, iron and zinc ions. In preferred hydroxyapatite powders according to the present invention, the proportion of calcium ions exchanged for foreign ions is at most 5 atom%, at most 3 atom%, or only at most 1 atom%. In certain embodiments of the invention, the hydroxyapatite from which the powder is formed is calcium-saturated hydroxyapatite with the stoichiometric formula Ca 5 (P0 4 ) 3 OH.
Bei anderen Ausführungsformen handelt es sich bei dem Hydroxylapatit um Calcium-defizitäres Hydroxylapatit mit der Formel Caio-x(P04)6-x(HP04)x(OH)2-x, wobei 0 < x < 2 ist. Die Bestimmung der Absättigung des Hydroxylapatits erfolgt per Röntgenfluoreszenzanalyse (z.B. Malvern Panalytical, Axios, WDXRF). Wenn die gemessene Absättigung < 3,33 beträgt, handelt es sich um ein Calcium-defizitäres Hydroxylapatit. Ab 3,33 bzw. darüber handelt sich um ein Calcium-gesättigtes Hydroxylapatit. In other embodiments, the hydroxyapatite is calcium-deficient hydroxyapatite with the formula Caio- x (P0 4 ) 6-x (HP0 4 ) x (OH) 2-x , where 0 <x <2. The saturation of the hydroxyapatite is determined by means of X-ray fluorescence analysis (e.g. Malvern Panalytical, Axios, WDXRF). If the measured saturation is <3.33, it is a calcium-deficient hydroxyapatite. From 3.33 or above it is a calcium-saturated hydroxyapatite.
Wenigstens 90 Gew.-% der Primärpartikel des erfindungsgemäßen Hydroxylapatit-Pulvers liegen zu Sekundärpartikeln agglomiert vor, vorzugsweise wenigstens 95 Gew.-% noch bevorzugter wenigstens 98 Gew.-% . Der Median der Größe der Sekundärpartikel ist > 1 ,0 pm. Bei bestimmten Ausführungsformen ist der Median der Sekundärpartikel > 10,0 pm oder gar > 100 pm. At least 90% by weight of the primary particles of the hydroxyapatite powder according to the invention are agglomerated to form secondary particles, preferably at least 95% by weight, more preferably at least 98% by weight. The median of the size of the secondary particles is> 1.0 pm. In certain embodiments, the median of the secondary particles is> 10.0 pm or even> 100 pm.
Die Obergrenze des Medians der Sekundärpartikel ist bei bestimmten Ausführungsformen < 50 mhi, < 40 mhi, < 30 min, < 20 min, < 15 min, < 10 min, < 9 miti, < 8 mhi, < 1 mhi, < 6 miti oder gar < 5 mhi. In certain embodiments, the upper limit of the median of the secondary particles is <50 mhi, <40 mhi, <30 min, <20 min, <15 min, <10 min, <9 miti, <8 mhi, <1 mhi, <6 miti or even <5 mhi.
Das erfindungsgemäße Hydroxylapatit-Pulver kann nach einem Verfahren erhalten werden, bei dem ein Reaktionsgemisch erzeugt wird, in dem Kalkmilch mit Phosphorsäure zu Hydroxylapatit umgesetzt wird, wobei dieses Verfahren insbesondere dadurch gekennzeichnet ist, dass man einen Verfahrenszyklus mit den folgenden Verfahrensschritten ausführt: a) Bereitstellen einer Suspension von Hydroxylapatit-Startpartikeln in Wasser, The hydroxylapatite powder according to the invention can be obtained by a process in which a reaction mixture is produced in which milk of lime is reacted with phosphoric acid to form hydroxylapatite, this process being particularly characterized in that a process cycle with the following process steps is carried out: a) providing a suspension of hydroxyapatite starting particles in water,
b) Zugeben von Kalkmilch und Phosphorsäure zu der Suspension, b) adding milk of lime and phosphoric acid to the suspension,
c) Umsetzen der Kalkmilch mit der Phosphorsäure in der Suspension zu Hydroxylapatit
bei einer Temperatur im Bereich von > 20 °C und < 105 °C und bei einem pH-Wert im Bereich von 6,0 bis 13,0, c) Reacting the milk of lime with the phosphoric acid in the suspension to form hydroxyapatite at a temperature in the range from> 20 ° C and <105 ° C and at a pH value in the range from 6.0 to 13.0,
d) Abtrennen wenigstens eines Teils der Hydroxylapatit-Partikel aus der Suspension, e) wenigstens einmal Wiederholen der Verfahrensschritte a) bis d), wobei entweder die in Verfahrensschritt d) abgetrennten Hydroxylapatit-Partikel als Hydroxylapatit-Startpartikel in Verfahrensschrit a) verwendet werden oder die in Verfahrensschritt d) in der Suspension verbleibenden Hydroxylapatit-Partikel, und d) separating at least some of the hydroxyapatite particles from the suspension, e) repeating method steps a) to d) at least once, either the hydroxyapatite particles separated in method step d) being used as hydroxyapatite starting particles in method step a) or the hydroxyapatite particles remaining in the suspension in process step d), and
f) Entnahme der Hydroxylapatit-Partikel aus dem Verfahrenszyklus, die im getrockneten Zustand einen Median der Primärpartikel > 0,1 pm aufweisen. f) Removal of the hydroxyapatite particles from the process cycle, which in the dried state have a median of the primary particles> 0.1 μm.
Die für die vorliegende Erfindung beanspruchten Vorteile werden bereits erreicht, wenn die Verfahrensschritte a) bis d) nur einmal wiederholt werden. Noch bessere Ergebnisse können jedoch erzielt werden, wenn diese Verfahrensschritte wenigstens dreimal wiederholt werden. The advantages claimed for the present invention are already achieved if method steps a) to d) are repeated only once. However, even better results can be achieved if these process steps are repeated at least three times.
Bei einer Ausführungsform der Erfindung wird das Verfahren im semi-kontinuierlichen Betrieb ausgeführt, wobei stets der Anteil der in Verfahrensschritt d) abgetrennten Hydroxylapatit-Partikel aus dem Prozess entnommen wird, der im getrockneten Zustand einen Median der Primärpartikel von > 0,10 pm aufweist, während der übrige Anteil in Verfahrensschritt a) erneut in Wasser suspendiert wird, um eine Suspension von Hydroxylapatit-Startpartikeln in Wasser bereitzustellen. In one embodiment of the invention, the process is carried out in semi-continuous operation, the proportion of the hydroxylapatite particles separated in process step d) always being removed from the process which, in the dried state, has a median of the primary particles of> 0.10 pm, while the remaining portion is resuspended in water in process step a) in order to provide a suspension of hydroxyapatite starter particles in water.
Bei einer alternativen Ausführungsform der Erfindung wird das Verfahren im voll-kontinuierlichen Betrieb ausgeführt, wobei in Verfahrensschritt d) kontinuierlich der Anteil an Hydroxyla- patit-Partikeln abgetrennt und aus dem Verfahrenszyklus entnommen wird, der im getrockneten Zustand einen Median der Primärpartikel von > 0,10 pm aufweist, während der übrige Anteil weiter im Verfahrenszyklus verbleibt. Die kontinuierliche Abtrennung und Entnahme erfolgt vorzugsweise mit einem Schrägklärer oder eine Zentrifuge (z.B.: Stülpzentrifuge oder Schubzentrifuge). In an alternative embodiment of the invention, the process is carried out in fully continuous operation, with the proportion of hydroxylapatite particles being continuously separated off in process step d) and removed from the process cycle, which in the dried state has a median of the primary particles of> 0, 10 pm, while the remaining portion remains in the process cycle. The continuous separation and removal is preferably carried out with an inclined clarifier or a centrifuge (e.g. inverted centrifuge or pusher centrifuge).
Bei einer bestimmten Ausführungsform werden im Verfahrensschritt a) Hydroxylapatit-Startpartikel mit einem Median von < 0,1 pm eingesetzt und die Verfahrensschritte a) bis e) wenigstens einmal wiederholt, um ein Hydroxylapatit-Pulver zu erhalten, dessen Primärpartikel einen Median von > 0,10 pm aufweisen und ein Aspektverhältnis von < 5, wobei die spezifische Oberfläche des Hydroxylapatit-Pulvers < 10 m2/g ist und die Schüttdichte > 550 g/l beträgt.
Bei einer besonderen Ausführungsform der Erfindung wird das Verfahren im kontinuierlichen Betrieb ausgeführt, wobei ein Anteil der in Verfahrensschritt d) abgetrennten Hydroxylapatit- Partikel, deren Primärpartikel einen Median von > 0,10 pm aufweisen und ein Aspektverhältnis von < 5 und deren spezifische Oberfläche < 10 m2/g und deren Schüttdichte > 550 g/l beträgt, aus dem Prozess entnommen wird, während der übrige Anteil in Verfahrensschritt a) erneut in Wasser suspendiert wird, um dann die wiederholten Verfahrensschritte b) bis e) zu durchlaufen. In a certain embodiment, hydroxyapatite starting particles with a median of <0.1 μm are used in method step a) and method steps a) to e) are repeated at least once in order to obtain a hydroxyapatite powder whose primary particles have a median of> 0, 10 μm and an aspect ratio of <5, the specific surface of the hydroxyapatite powder being <10 m 2 / g and the bulk density being> 550 g / l. In a particular embodiment of the invention, the process is carried out in continuous operation, with a proportion of the hydroxylapatite particles separated in process step d) whose primary particles have a median of> 0.10 μm and an aspect ratio of <5 and their specific surface area <10 m 2 / g and whose bulk density is> 550 g / l, is removed from the process, while the remaining portion in process step a) is resuspended in water in order to then go through the repeated process steps b) to e).
Die Umsetzung der Kalkmilch mit der Phosphorsäure soll möglichst gleichmäßig und kontrolliert erfolgen. Für den Erfolg der vorliegenden Erfindung ist es daher entscheidend, dass die Temperatur im Reaktionsgemisch oberhalb von 20 °C liegt und unterhalb von 105 °C. Bei bestimmten Ausführungsformen der Erfindung erfolgt das Umsetzen der Kalkmilch mit der Phosphorsäure in dem Reaktionsgemisch zu Hydroxylapatit bei einer Temperatur im Bereich von > 60 °C und < 100 °C oder bei einer Temperatur im Bereich von > 80 °C und < 100 °C. The conversion of the milk of lime with the phosphoric acid should be as uniform and controlled as possible. It is therefore crucial for the success of the present invention that the temperature in the reaction mixture is above 20 ° C and below 105 ° C. In certain embodiments of the invention, the milk of lime is reacted with the phosphoric acid in the reaction mixture to form hydroxyapatite at a temperature in the range from> 60 ° C and <100 ° C or at a temperature in the range from> 80 ° C and <100 ° C.
Für den Erfolg der vorliegenden Erfindung ist es auch entscheidend, dass der pH-Wert im Bereich von 6,0-13,0 liegt. Bei einem pH-Wert von < 6,0 fällt Calciumhydrogenphosphat (CaHPC ) oder Calciumhydrogenphosphatdihydrat (CaHPC>4 *2 H2O) aus. Bei bestimmten Ausführungsformen der Erfindung erfolgt das Umsetzen der Kalkmilch mit der Phosphorsäure in dem Reaktionsgemisch zu Hydroxylapatit bei einem pH-Wert im Bereich von 7,0 bis 1 1 ,0, da unter bestimmten Bedingungen oberhalb von pH 1 1 ,0 vermehrt Ca(OH)2 als Nebenphase auftreten kann. Bei einer alternativen Ausführungsformen der Erfindung erfolgt das Umsetzen zu Hydroxylapatit bei einem pH-Wert im Bereich von 7,0 bis 9,0, da es unter bestimmten Bedingungen oberhalb von pH 9,0 zumindest teilweise zu Einschlüssen von Ca(OH)2 kommen kann. It is also critical to the success of the present invention that the pH be in the range of 6.0-13.0. Calcium hydrogen phosphate (CaHPC) or calcium hydrogen phosphate dihydrate (CaHPC> 4 * 2 H2O) precipitate at a pH value of <6.0. In certain embodiments of the invention, the milk of lime is reacted with the phosphoric acid in the reaction mixture to form hydroxyapatite at a pH in the range from 7.0 to 11.0, since under certain conditions above pH 11.0, more Ca (OH ) 2 can occur as a minor phase. In an alternative embodiment of the invention, the conversion to hydroxyapatite takes place at a pH in the range from 7.0 to 9.0, since, under certain conditions above pH 9.0, inclusions of Ca (OH) 2 can occur at least partially .
Bei einer bestimmten Ausführungsform der Erfindung wird die Umsetzung von Phosphorsäure und Kalkmilch im Reaktionsgemisch (Verfahrensschritt c)) bei Atmosphärendruck durchgeführt. Falls gewünscht, kann jedoch auch bei leicht erhöhtem Druck gearbeitet werden, vorzugsweise bis zu einem Überdruck von 1 bar. In a certain embodiment of the invention, the conversion of phosphoric acid and milk of lime in the reaction mixture (process step c)) is carried out at atmospheric pressure. If desired, however, it is also possible to work at slightly increased pressure, preferably up to an excess pressure of 1 bar.
Die nach dem erfindungsgemäßen Verfahren erhaltenen Partikel werden im letzten Verarbeitungsschritt mit Wasser gewaschen, durch Filtration oder Zentrifugation abgetrennt und getrocknet. Wie dies im Einzelnen zu geschehen hat, ist dem Fachmann bekannt und bedarf daher keiner weiteren Ausführungen.
Eines der Edukte des erfindungsgemäßen Verfahrens ist Phosphorsäure (H3PO4). Bei bestimmten Ausführungsformen handelt es sich bei der eingesetzten Phosphorsäure um verdünnte Phosphorsäure mit einer Konzentration von 5 bis 25 Vol.-% Phosphorsäure in Wasser. Niedrige Phosphorsäurekonzentrationen begünstigen das Keimwachstum, führen gleichzeitig jedoch zu größeren Volumina des Reaktionsgemisches. Bei bestimmten Ausführungsformen liegt die Konzentration der eingesetzten Phosphorsäure daher im Bereich von 10 bis 25 Vol.- % Phosphorsäure in Wasser oder im Bereich von 15 bis 25 Vol.-% Phosphorsäure in Wasser. In the last processing step, the particles obtained by the process according to the invention are washed with water, separated off by filtration or centrifugation and dried. How this has to be done in detail is known to the person skilled in the art and therefore does not require any further explanations. One of the starting materials of the process according to the invention is phosphoric acid (H 3 PO4). In certain embodiments, the phosphoric acid used is dilute phosphoric acid with a concentration of 5 to 25% by volume of phosphoric acid in water. Low phosphoric acid concentrations promote the growth of germs, but at the same time lead to larger volumes of the reaction mixture. In certain embodiments, the concentration of the phosphoric acid used is therefore in the range from 10 to 25% by volume of phosphoric acid in water or in the range from 15 to 25% by volume of phosphoric acid in water.
Das zweite Edukt des erfindungsgemäßen Verfahrens ist Kalkmilch (Suspension von Ca(OH)2 in Wasser). Bei bestimmten Ausführungsformen der Erfindung weist die Kalkmilch auf oxidischer Basis eine Konzentration von 2 bis 20 Gew.-%, vorzugsweise von 8 bis 12 Gew.-% auf. The second starting material of the process according to the invention is milk of lime (suspension of Ca (OH) 2 in water). In certain embodiments of the invention, the oxide-based milk of lime has a concentration of 2 to 20% by weight, preferably 8 to 12% by weight.
Gemäß der vorliegenden Erfindung können im Verfahrensschritt b) die Kalkmilch und die Phosphorsäure nacheinander zugegeben werden, wobei der zeitliche Abstand bei der Zugabe dieser beiden Edukte möglichst gering sein sollte. Vorzugsweise werden Kalkmilch und Phosphorsäure jedoch gleichzeitig zu der Vorlage zugegeben. According to the present invention, the milk of lime and the phosphoric acid can be added one after the other in process step b), the time interval between the addition of these two starting materials being as short as possible. However, milk of lime and phosphoric acid are preferably added to the initial charge at the same time.
Die Umsetzung von Kalkmilch mit Phosphorsäure erfolgt nach dem erfindungsgemäßen Verfahren in Gegenwart von Hydroxylapatit-Startpartikeln, deren Partikelgröße durch einen Median von < 0,1 pm gekennzeichnet ist. Diese Partikel weisen bei bestimmten Ausführungsformen eine Schüttdichte im Bereich von 200 bis 350 g/l auf und eine spezifische Oberfläche im Bereich von 15 bis 50 m2/g. The reaction of milk of lime with phosphoric acid takes place according to the process according to the invention in the presence of hydroxyapatite starter particles, the particle size of which is characterized by a median of <0.1 μm. In certain embodiments, these particles have a bulk density in the range from 200 to 350 g / l and a specific surface area in the range from 15 to 50 m 2 / g.
Bei dem erfindungsgemäßen Verfahren werden durch die wiederholte Aufschichtung von Hyd- roxylapatit-Lagen während des Verfahrensschrittes c), Primärpartikel der gewünschten Größe und Gestalt erhalten. Dies erfolgt dadurch, dass die dem Reaktionsgemisch zugegebene Kalkmilch mit der dem Reaktionsgemisch zugegebenen Phosphorsäure in situ zu Hydroxylapatit umgesetzt wird. In the process according to the invention, primary particles of the desired size and shape are obtained through the repeated stacking of hydroxyapatite layers during process step c). This takes place in that the milk of lime added to the reaction mixture is reacted in situ with the phosphoric acid added to the reaction mixture to form hydroxyapatite.
Die wiederholte Umsetzung von jeweils frisch zu gegebener Kalkmilch und frisch zugegebener Phosphorsäure erfolgt im Verfahrensschritt c) sowohl bei der erstmaligen als auch bei jeder wiederholten Ausführung unter rühren. Die mechanische Belastung beim Rühren soll möglichst gering gehalten werden. Dementsprechend beträgt bei bestimmten Ausführungsformen des erfindungegemäßen Verfahrens die maximale Geschwindigkeit des in der Rotationsebene äußersten Abschnitts des Rührers < 2 m/s, noch bevorzugter < 1 m/s und besonders bevorzugt < 0,5 m/s. Bei zu hoher mechanischer Belastung des Reaktionsgemisches würden neue Kristallisationskeime entstehen, was den erfindungsgemäßen Prozess der Aufschichtung weiterer Hydroxylapatit-Lagen auf bereits bestehende Partikel behindern würde.
Die wiederholte Umsetzung von jeweils frisch zu gegebener Kalkmilch und frisch zugegebener Phosphorsäure erfolgt im Verfahrensschritt c) sowohl bei der erstmaligen als auch bei jeder wiederholten Ausführung vorzugweise über einen gewissen Zeitraum. The repeated conversion of freshly added milk of lime and freshly added phosphoric acid takes place in process step c) both for the first time and for each repeated execution with stirring. The mechanical stress during stirring should be kept as low as possible. Accordingly, in certain embodiments of the method according to the invention, the maximum speed of the section of the stirrer outermost in the plane of rotation is <2 m / s, more preferably <1 m / s and particularly preferably <0.5 m / s. If the mechanical stress on the reaction mixture is too high, new crystallization nuclei would arise, which would hinder the process according to the invention of layering further hydroxylapatite layers on existing particles. The repeated conversion of freshly added milk of lime and freshly added phosphoric acid takes place in process step c) both for the first time and for each repeated execution, preferably over a certain period of time.
Das mit der vorliegenden Erfindung bereitgestellte Hydroxylapatit-Pulver kann den ver schiedensten Anwendungen zugeführt werden. Bei einer Ausführungsform der Erfindung wird das erfindungsgemäße Hydroxylapatit-Pulver zur Anreicherung von Nahrungsmitteln, wie z. B. Milch oder Käse, mit Calcium verwendet. Bei einer weiteren Ausführungsform wird das erfin dungsgemäße Hydroxylapatit-Pulver als Freifließmittel in Nahrungsmitteln zur Verbesserung von deren Fließeigenschaften verwendet. In Betracht kommt auch die kombinierte Verwen dung, d.h. sowohl als Freifließmittel als auch zur Calciumanreicherung. The hydroxyapatite powder provided by the present invention can be put to various uses. In one embodiment of the invention, the hydroxylapatite powder according to the invention is used for fortifying foods, such as. B. milk or cheese, used with calcium. In a further embodiment, the hydroxyapatite powder according to the invention is used as a free-flowing agent in foodstuffs to improve their flow properties. Combined use is also contemplated, i.e. both as a free-flowing agent and for calcium enrichment.
Bei einer anderen Ausführungsform wird das erfindungsgemäße Hydroxylapatit-Pulver als Füllstoff für Kunststoffe und Keramik verwendet oder als Schleifmittel in Zahnpasta oder als Hartstoff in Bremsbelägen. In another embodiment, the hydroxyapatite powder according to the invention is used as a filler for plastics and ceramics or as an abrasive in toothpaste or as a hard material in brake linings.
Ausführungsbeispiele Embodiments
Die Beispiele 1.1 - 1.4 beschreiben unterschiedliche Herstellungsverfahren für Hydroxylapa- titpulver (HAP). Examples 1.1-1.4 describe different manufacturing processes for hydroxylapatite powder (HAP).
Die Analysenergebnisse von den so hergestellten Materialien befinden sich im Anschluss in einer tabellarischen Aufstellung. The analysis results of the materials produced in this way are then shown in a table.
1.1 Herkömmliches Verfahren 1.1 Traditional method
In einem Kessel wird eine wässrige Suspension aus Ca(OH)2 (rechnerischer Gehalt von 10% CaO) auf 80°C erhitzt. Dann wird die entsprechende Menge 20%iger H3PO4 langsam hinzu gegeben bis zum Erreichen eines pH-Wertes von 7. Die Suspension wird für weitere 15 min. gerührt. Anschließend abfiltriert gewaschen und getrocknet. An aqueous suspension of Ca (OH) 2 (calculated content of 10% CaO) is heated to 80 ° C. in a kettle. Then the appropriate amount of 20% H3PO4 is slowly added until a pH of 7. The suspension is left for a further 15 min. touched. Then filtered off, washed and dried.
1.2 Erfindungsgemäßes Verfahren (Fällung auf Hydroxylapatit) 1.2 Process according to the invention (precipitation on hydroxyapatite)
In einem Kessel wird eine wässrige Suspension aus HAP (Material aus 1.1) mit einem Fest stoffgehalt von 13% auf 90°C erhitzt, die Vorlagemenge an HAP beträgt 10% der gewünschten Zielmenge. Dann werden gleichzeitig Kalkmilch mit einem rechnerischen Gehalt von 10%
CaO und 20%ige Phosphorsäure hinzugegeben unter Einhaltung eines spezifischen pH-Wer- tes im Bereich von 7,0 bis 9,0. Die Suspension wird für weitere 15 min. gerührt. Anschließend werden 90% der Suspension abfiltriert gewaschen und getrocknet. Die Versuche zur gleich zeitigen Fällung wurden nach der ersten Fällung (V1) noch siebenmal wiederholt (V2 - V8), dabei dienten jeweils die verbleibenden 10% als Vorlage für den für die nächste Fällung nach dieser Methode. An aqueous suspension of HAP (material from 1.1) with a solids content of 13% is heated to 90 ° C. in a kettle; the amount of HAP initially charged is 10% of the desired target amount. Then milk of lime with a calculated content of 10% CaO and 20% phosphoric acid added while maintaining a specific pH value in the range from 7.0 to 9.0. The suspension is for a further 15 min. touched. 90% of the suspension is then filtered off, washed and dried. The attempts at simultaneous precipitation were repeated seven times (V2-V8) after the first precipitation (V1), the remaining 10% serving as a template for the next precipitation by this method.
1.3. Vergleichsverfahren (Fällung auf Ca(OH)2) 1.3. Comparison process (precipitation on Ca (OH) 2)
100 mL Kalkmilch werden in einem 2 L Reaktor vorgelegt, und diese von einer pH-Elektrode erfasst. Anschließend wird Kalkmilch (Gehalt: 10% CaO) bei 20 rpm über eine Schlauchpumpe zugeben, gleichzeitig wird über ein Prozessleitsystem Phosphorsäure (20%) so zugegeben, dass während der Fällung ein bestimmter pH-Wert vorliegt. Nach erreichen >11 Füllmarke wurde 400 ml des Ansatzes abgenommen und der Rest (im PLS) mit Phosphorsäure auf einen pH von 7 eingestellt. Die Versuche wurden mit den Fällungs-pH-Werten 10, 9, 8, 7 (V1 - V8) durchgeführt. 100 mL milk of lime are placed in a 2 L reactor and this is recorded by a pH electrode. Then milk of lime (content: 10% CaO) is added at 20 rpm using a peristaltic pump, at the same time phosphoric acid (20%) is added via a process control system so that a certain pH value is present during the precipitation. After reaching> 11 fill mark, 400 ml of the mixture was removed and the remainder (in the PLS) was adjusted to a pH of 7 with phosphoric acid. The experiments were carried out with the precipitation pH values 10, 9, 8, 7 (V1 - V8).
1.4 Vergleichsverfahren (Sinterverfahren) 1.4 Comparison process (sintering process)
Material aus 1.1 wird durch thermische Behandlung zusammengesintert. Dafür wurde das Ma terial in Alusint-Tiegel auf 300, 500 und 900 °C für jeweils 12 h erhitzt (V1 - V3). Material from 1.1 is sintered together by thermal treatment. For this purpose, the material was heated in Alusint crucibles to 300, 500 and 900 ° C for 12 h each (V1 - V3).
Analysemethoden und Ergebnisse Analysis methods and results
Die nach den Beispielen 1 .1 - 1 .4 hergestellten Materialien wurden mit den folgenden Metho den analysiert: The materials produced according to Examples 1 .1 - 1 .4 were analyzed using the following methods:
Röntgenbeugung (XRD, Bruker D8 Advance, CuKa, 40kV; 40,0 mA; l 1 ,5406 Ä; LynxEye- Detektor) X-ray diffraction (XRD, Bruker D8 Advance, CuKa, 40kV; 40.0 mA; l 1, 5406 Ä; LynxEye detector)
Partikelgrößenverteilungen (PSD) durch dynamische Lichstreuung („Horiba“) sowohl Volumen- als auch Partikelgrößen-basiert, spezifische Oberfläche nach dem BET-Verfahren durch N2-Absorption (DIN ISO 9277). Particle size distributions (PSD) through dynamic light scattering ("Horiba") based on both volume and particle size, specific surface area according to the BET method through N2 absorption (DIN ISO 9277).
Form und Größe per Rasterelektronenmikroskopaufnahmen (REM).
1. Physikalische Spezifikationen Shape and size by scanning electron microscope images (SEM). 1. Physical specifications
Eine Zusammenstellung der experimentell bestimmten Analysenwerte für die nach den Beispielen hergestellten Materialien befindet sich in den nachfolgenden Tabellen 1 und 2. A compilation of the experimentally determined analytical values for the materials produced according to the examples is given in Tables 1 and 2 below.
Tabelle 1 : Übersicht über die Analysenwerte von den Experimenten 1.1-1.2. Table 1: Overview of the analysis values from experiments 1.1-1.2.
Tabelle 2: Übersicht über die Analysenwerte von den Experimenten 1.3-1.4. Table 2: Overview of the analysis values from experiments 1.3-1.4.
granuliertes Produkt
2. Untersuchungen zu den Freifließeigenschaften granulated product 2. Investigations into the free-flow properties
Erfindungsgemäß erzeugtes Hydroxylapatit-Pulver wurde als Freifließmittel für zwei unterschiedliche Kaffeeweißer (VB 30A und VG 80C) verwendet und mit anderen Freifließmittel (B-TCP = beta- Tricalciumphosphat; E551 = Nano-SiC>2) verglichen. Hydroxylapatite powder produced according to the invention was used as a free-flowing agent for two different coffee whiteners (VB 30A and VG 80C) and compared with other free-flowing agents (B-TCP = beta-tricalcium phosphate; E551 = nano-SiC> 2).
Ermittelt wurde der maximal erreichbare Böschungswinkel des aufgeschütteten Materials, und die Ergebnisse sind unten in der Tabelle 3 zusammengefasst. Ein Winkel von 31-40° steht für gute Fließeigenschaften, ein Winkel von 41 bis 45° für annehmbare Fließeigenschaften und ein Winkel von 46-55° für schlechte Fließeigenschaften. The maximum attainable angle of repose of the heaped material was determined and the results are summarized in Table 3 below. An angle of 31-40 ° represents good flow properties, an angle of 41 to 45 ° represents acceptable flow properties and an angle of 46-55 ° represents poor flow properties.
Tabelle 3: Übersicht über Schüttwinkel der Freifließversuche Table 3: Overview of the angle of repose of the free-flow tests
Die Versuchsergebnisse zeigen, dass durch den Zusatz von erfindungsgemäßem Hydroxylapatit- Pulver den verschiedenen Kaffeeweißern gute Fließeigenschaften verliehen werden.
The test results show that the addition of hydroxyapatite powder according to the invention gives the various coffee whiteners good flow properties.
Claims
1. Hydroxylapatit-Pulver zusammengesetzt aus Primärpartikeln, dadurch gekennzeichnet, daß der Median der Primärpartikel bei > 0,10 pm liegt und das Aspektverhältnis der Primärpartikel < 5 beträgt, wobei die spezifische Oberfläche des Hydroxylapatit-Pulvers < 10 m2/g ist und die Schüttdichte > 550 g/l beträgt. 1. Hydroxyapatite powder composed of primary particles, characterized in that the median of the primary particles is> 0.10 pm and the aspect ratio of the primary particles is <5, the specific surface area of the hydroxyapatite powder being <10 m 2 / g and the Bulk density is> 550 g / l.
2. Hydroxylapatit-Pulver nach Anspruch 1 , dadurch gekennzeichnet, daß es zu wenigstens 95 Gew.-% aus CasCPO^OH besteht. 2. Hydroxyapatite powder according to claim 1, characterized in that it consists of at least 95 wt .-% CasCPO ^ OH.
3. Hydroxylapatit-Pulver nach Anspruch 1 , dadurch gekennzeichnet, daß das Hydroxylapatit calciumgesättigtes Hydroxylapatit mit der Formel CasCPO^OH ist oder calciumdefizitäres Hydroxylapatit mit der Formel Caio-x(P04)6-x(HP04)x(OH)2-x ist, wobei 0<x<2. 3. Hydroxyapatite powder according to claim 1, characterized in that the hydroxyapatite is calcium-saturated hydroxyapatite with the formula CasCPO ^ OH or calcium-deficient hydroxyapatite with the formula Caio- x (P04) 6- x (HP04) x (OH) 2- x , where 0 <x <2.
4. Hydroxylapatit-Pulver nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß die Primärpartikel des Pulvers zu Sekundärpartikeln agglomeriert sind, wobei der Median der Größe der Sekundärpartikel > 1 ,0 pm ist. 4. Hydroxyapatite powder according to one of claims 1 to 3, characterized in that the primary particles of the powder are agglomerated to form secondary particles, the median of the size of the secondary particles being> 1.0 μm.
5. Verfahren zur Herstellung eines Hydroxylapatit-Pulvers, bei dem man ein Reaktionsgemisch erzeugt, in dem Kalkmilch mit Phosphorsäure zu Hydroxylapatit umgesetzt wird, dadurch gekennzeichnet, daß man einen Verfahrenszyklus mit den folgenden Verfahrensschritten ausführt: a) Bereitstellen einer Suspension von Hydroxylapatit-Startpartikeln in Wasser, b) Zugeben von Kalkmilch und Phosphorsäure zu der Suspension, 5. A process for producing a hydroxylapatite powder, in which a reaction mixture is produced in which milk of lime is reacted with phosphoric acid to form hydroxylapatite, characterized in that a process cycle is carried out with the following process steps: a) providing a suspension of hydroxylapatite starter particles in Water, b) adding milk of lime and phosphoric acid to the suspension,
c) Umsetzen der Kalkmilch mit der Phosphorsäure in der Suspension zu Hydroxylapatit c) Reacting the milk of lime with the phosphoric acid in the suspension to form hydroxyapatite
bei einer Temperatur im Bereich von > 20 °C und < 105 °C und bei einem pH-Wert im Bereich von 6,0 bis 13,0, at a temperature in the range from> 20 ° C and <105 ° C and at a pH value in the range from 6.0 to 13.0,
d) Abtrennen wenigstens eines Teils der Hydroxylapatit-Partikel aus der Suspension, e) wenigstens einmal Wiederholen der Verfahrensschritte a) bis d), wobei entweder die in Verfahrensschritt d) abgetrennten Hydroxylapatit-Partikel als Hydroxylapatit- Startpartikel in Verfahrensschrit a) verwendet werden oder die in Verfahrensschritt d) in der Suspension verbleibenden Hydroxylapatit-Partikel, und d) separating at least a part of the hydroxyapatite particles from the suspension, e) repeating method steps a) to d) at least once, either the hydroxyapatite particles separated in method step d) being used as hydroxyapatite starter particles in method step a) or the hydroxyapatite particles remaining in the suspension in process step d), and
f) Entnahme der Hydroxylapatit-Partikel aus dem Verfahrenszyklus, die im getrockneten Zustand einen Median der Primärpartikel > 0,1 pm aufweisen.
f) Removal of the hydroxyapatite particles from the process cycle, which in the dried state have a median of the primary particles> 0.1 μm.
6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, daß bei dem Verfahren die Verfah rensschritte a) bis d) wenigstens 3 mal wiederholt werden. 6. The method according to claim 5, characterized in that the procedural steps a) to d) are repeated at least 3 times in the method.
7. Verfahren nach einem der Ansprüche 5 und 6, dadurch gekennzeichnet, das Verfahren entweder 7. The method according to any one of claims 5 and 6, characterized in that either the method
■ im semi-kontinuierlichen Betrieb ausgeführt wird, wobei stets der Anteil der in Ver fahrensschritt d) abgetrennten Hydroxylapatit-Partikel aus dem Prozess entnom men wird, der im getrockneten Zustand einen Median der Primärpartikel von > 0,10 pm aufweist, während der übrige Anteil in Verfahrensschritt a) erneut in Wasser suspendiert wird, um eine Suspension von Hydroxylapatit-Startpartikeln in Wasser bereitzustellen, oder ■ is carried out in semi-continuous operation, the proportion of the hydroxylapatite particles separated in process step d) always being removed from the process, which in the dried state has a median of the primary particles of> 0.10 pm, while the remaining proportion is resuspended in water in process step a) in order to provide a suspension of hydroxyapatite starter particles in water, or
■ im voll-kontinuierlichen Betrieb ausgeführt, wobei in Verfahrensschritt d) kontinuier lich der Anteil an Hydroxylapatit-Partikeln abgetrennt und aus dem Verfahrenszyk lus entnommen wird, der im getrockneten Zustand einen Median der Primärpartikel von > 0,10 pm aufweist, während der übrige Anteil weiter im Verfahrenszyklus ver bleibt. ■ carried out in fully continuous operation, whereby in process step d) continuously the proportion of hydroxylapatite particles is separated off and removed from the process cycle, which in the dried state has a median of the primary particles of> 0.10 pm, while the remaining proportion remains in the process cycle.
8. Verfahren nach einem der Ansprüche 5 bis 7, dadurch gekennzeichnet, daß die Kalkmilch und die Phosphorsäure in Stufe c) gleichzeitig zugegeben werden. 8. The method according to any one of claims 5 to 7, characterized in that the milk of lime and the phosphoric acid are added simultaneously in step c).
9. Verfahren nach einem der Ansprüche 5 bis 8, dadurch gekennzeichnet, daß die Phosphor säure verdünnte Phosphorsäure mit einer Konzentration von 5-25 Vol.-% Phosphorsäure in Wasser ist. 9. The method according to any one of claims 5 to 8, characterized in that the phosphoric acid is dilute phosphoric acid with a concentration of 5-25 vol .-% phosphoric acid in water.
10. Verfahren nach einem der Ansprüche 5 bis 9, dadurch gekennzeichnet, daß die Kalkmilch auf oxidischer Basis eine Konzentration von 2-20 Gew.-% % aufweist. 10. The method according to any one of claims 5 to 9, characterized in that the oxide-based milk of lime has a concentration of 2-20 wt .-%.
1 1. Verwendung des Hydroxylapatit-Pulvers nach einem der Ansprüche 1 bis 4 oder des nach dem Verfahren nach einem der Ansprüche 5 bis 10 erhaltenen Hydroxylapatit-Pulvers zur Anreicherung von Nahrungsmitteln mit Calcium und/oder als Freifließmittel in Nahrungs mitteln zur Verbesserung von deren Fließeigenschaften. 1 1. Use of the hydroxyapatite powder according to any one of claims 1 to 4 or the hydroxyapatite powder obtained by the method according to any one of claims 5 to 10 for enriching foods with calcium and / or as free-flowing agents in foods to improve their flow properties .
12. Verwendung des Hydroxylapatit-Pulvers nach einem der Ansprüche 1 bis 4 oder des nach dem Verfahren nach einem der Ansprüche 5 bis 10 erhaltenen Hydroxylapatit-Pulvers als Füllstoff für Kunststoffe und Keramiken, als Schleifmittel in Zahnpasta oder als Hartstoff in Bremsbelägen.
12. Use of the hydroxyapatite powder according to one of claims 1 to 4 or the hydroxyapatite powder obtained by the method according to one of claims 5 to 10 as a filler for plastics and ceramics, as an abrasive in toothpaste or as a hard material in brake linings.
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DE102019109143.8A DE102019109143A1 (en) | 2019-04-08 | 2019-04-08 | Hydroxyapatite powder and process for its manufacture |
PCT/EP2020/059070 WO2020212131A1 (en) | 2019-04-08 | 2020-03-31 | Hydroxyapatite powder and method for producing same |
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JP2575170B2 (en) * | 1988-03-16 | 1997-01-22 | 株式会社トクヤマ | Method for producing spherical hydroxyapatite |
DE4037103C1 (en) * | 1990-11-22 | 1992-01-09 | Bk Ladenburg Gmbh Gesellschaft Fuer Chemische Erzeugnisse, 6802 Ladenburg, De | |
DE4232443C1 (en) * | 1992-09-28 | 1993-09-23 | Bk Ladenburg Gmbh Gesellschaft Fuer Chemische Erzeugnisse, 68526 Ladenburg, De | |
RU2122520C1 (en) * | 1996-10-31 | 1998-11-27 | Акционерное общество закрытого типа "ОСТИМ" | Method of preparing hydroxyapatite suspension |
DE19858662A1 (en) | 1998-12-18 | 2000-06-21 | Henkel Kgaa | Nanomolecular suspension of poorly-soluble calcium salts is stabilized by water-soluble surfactant or protective colloid, useful as remineralization agent in toothpaste |
DE19916155A1 (en) * | 1999-04-11 | 2000-11-16 | Orochemie Duerr & Pflug Gmbh & | Suspension for the treatment of natural hard tissue |
EP1401762A1 (en) | 2001-06-22 | 2004-03-31 | Basf Aktiengesellschaft | Rod shaped apatite crystals with a specific length-to-width ratio |
FR2857658B1 (en) * | 2003-07-16 | 2006-09-22 | Rhodia Chimie Sa | NOVEL CALCIUM PHOSPHATE GRANULES OF THE HYDROXYAPATITE TYPE, PROCESS FOR THEIR PREPARATION AND THEIR APPLICATIONS |
US7998219B2 (en) * | 2005-01-04 | 2011-08-16 | Rutgers, The State University Of New Jersey | Hydroxyapatite with controllable size and morphology |
EP2029480B1 (en) * | 2006-05-30 | 2017-05-03 | Coswell S.p.A. | Biologicallly active nanoparticles of a carbonate-substituted hydroxyapatite, process for their preparation and compositions incorporating the same |
US8974848B1 (en) * | 2008-06-26 | 2015-03-10 | Barry W. Carothers | Ingestible product and method for enhancing the appearance and quality of teeth in-vivo |
IT1400739B1 (en) * | 2009-06-02 | 2013-07-02 | Hoya Corp | METHOD FOR THE PRODUCTION OF POWDER, DUST AND APPARATUS APPARATUS |
CN103096840A (en) * | 2010-07-14 | 2013-05-08 | 密苏里大学学监 | Polymer composites and fabrications thereof |
GB201016970D0 (en) * | 2010-10-08 | 2010-11-24 | Univ Leeds | Composition |
DE102014115518A1 (en) * | 2014-10-24 | 2016-04-28 | orochemie GmbH + Co. KG | Dental polishing and cleaning paste |
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