US20040171471A1 - Rod shaped apatite crystals with a specific length-to-width ratio - Google Patents
Rod shaped apatite crystals with a specific length-to-width ratio Download PDFInfo
- Publication number
- US20040171471A1 US20040171471A1 US10/480,809 US48080903A US2004171471A1 US 20040171471 A1 US20040171471 A1 US 20040171471A1 US 48080903 A US48080903 A US 48080903A US 2004171471 A1 US2004171471 A1 US 2004171471A1
- Authority
- US
- United States
- Prior art keywords
- crystals
- rod
- fluoride
- shaped
- shaped apatite
- 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.)
- Abandoned
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 141
- 229910052586 apatite Inorganic materials 0.000 title claims abstract description 51
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[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 VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 55
- 230000008569 process Effects 0.000 claims abstract description 41
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 40
- 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 40
- 239000006185 dispersion Substances 0.000 claims abstract description 34
- -1 hydroxide ions Chemical class 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 229910052587 fluorapatite Inorganic materials 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 239000011575 calcium Substances 0.000 claims description 12
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 210000000988 bone and bone Anatomy 0.000 claims description 9
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- 239000000920 calcium hydroxide Substances 0.000 claims description 6
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 6
- 229910001424 calcium ion Inorganic materials 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 239000011775 sodium fluoride Substances 0.000 claims description 5
- 235000013024 sodium fluoride Nutrition 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 239000000606 toothpaste Substances 0.000 claims description 5
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
- 229910001634 calcium fluoride Inorganic materials 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000002324 mouth wash Substances 0.000 claims description 3
- 229940112822 chewing gum Drugs 0.000 claims description 2
- 235000015218 chewing gum Nutrition 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 230000007547 defect Effects 0.000 claims description 2
- 239000007943 implant Substances 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims description 2
- 229940051866 mouthwash Drugs 0.000 claims description 2
- 239000011698 potassium fluoride Substances 0.000 claims description 2
- 235000003270 potassium fluoride Nutrition 0.000 claims description 2
- 230000000395 remineralizing effect Effects 0.000 claims description 2
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 229940034610 toothpaste Drugs 0.000 claims 1
- 239000000725 suspension Substances 0.000 description 15
- 159000000007 calcium salts Chemical class 0.000 description 9
- 239000011148 porous material Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- 210000003298 dental enamel Anatomy 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 235000004252 protein component Nutrition 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000033558 biomineral tissue development Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 230000001788 irregular Effects 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 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 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 2
- GFIKIVSYJDVOOZ-UHFFFAOYSA-L calcium;fluoro-dioxido-oxo-$l^{5}-phosphane Chemical class [Ca+2].[O-]P([O-])(F)=O GFIKIVSYJDVOOZ-UHFFFAOYSA-L 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 208000002925 dental caries Diseases 0.000 description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 208000018035 Dental disease Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000014151 Stomatognathic disease Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000004334 fluoridation Methods 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000007970 homogeneous dispersion Substances 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000011164 primary particle Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/064—Chewing gum characterised by the composition containing organic or inorganic compounds containing inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/15—Compositions characterised by their physical properties
- A61K6/17—Particle size
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/60—Preparations for dentistry comprising organic or organo-metallic additives
- A61K6/69—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
- A61K6/838—Phosphorus compounds, e.g. apatite
-
- 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
- A61K8/20—Halogens; Compounds thereof
- A61K8/21—Fluorides; Derivatives thereof
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/32—Phosphorus-containing materials, e.g. apatite
-
- 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
- C01B25/322—Preparation by neutralisation of orthophosphoric acid
-
- 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
- C01B25/455—Phosphates containing halogen
Definitions
- the invention relates to rod-shaped apatite crystals which have a length-to-breadth ratio of >5 and in which the ratio of hydroxide ions to fluoride ions based on the total amount of the crystals can be simply varied. Furthermore, the invention relates to dispersions which contain such rod-shaped apatite crystals, and to a process for the preparation of the dispersions or of the apatite crystals.
- the dental enamel just like human bone, consists mainly of hydroxyapatite. Owing to mechanical stress on the teeth (e.g. when eating or else alternatively when brushing the teeth), fissures and channels result in the dental enamel, which expose pores in the interior of the tooth. Substances can rapidly penetrate into the interior of the tooth through these pores and irritate the dental nerve, as a result of which the teeth become sensitive to sweetness, heat or cold. Moreover, in the case of bacterial attack caries forms in the fissures or in the pores, which is known extensively as a very dangerous dental disease.
- a problem is the provision of rod-shaped (hydroxy)apatite crystals which make possible an effective adsorption on the tooth surface on account of an improved length-to-breadth ratio.
- the processes known hitherto for the preparation of apatite crystals usually yield crystals of spherical and irregular shape having particle sizes of >5 ⁇ m.
- processes have been published with which, in addition to the irregular and spherical shapes, rod-shaped apatite crystals having particle sizes in the submicrometer range can also be produced.
- WO 00/37033 describes suspensions of only slightly water-soluble calcium phosphates, calcium fluorides and calcium fluorophosphates, and their use in dental care compositions.
- the calcium salts contained in the suspensions are prepared by precipitation in an alkaline medium, the calcium salts being obtained in the form of crystals (primary particles) having thicknesses (diameters) of 0.005 to 0.05 ⁇ m and lengths of 0.01 to 0.15 ⁇ m.
- the precipitation of the calcium salts is carried out in the presence of agglomeration inhibitors, such as water-soluble surfactants or water-soluble polymeric protective colloids.
- suspensions of hydroxyapatite crystals and fluorine-doped hydroxyapatite crystals can also be prepared.
- the calcium salt crystals prepared in this way in some cases have rod-shaped structures.
- Inherent in the method is the disadvantage that on account of the overlapping length and breadth values of the crystals a numerically large amount of crystals is also produced whose length-to-breadth ratio is in the range from 1 to 2, i.e. these crystals have no pronounced rod form or only a slightly pronounced rod form.
- composite materials which comprise calcium salts which are poorly soluble in water, such as calcium phosphates and calcium fluorophosphates, and a protein component.
- the calcium salts which also include hydroxyapatite, fluoroapatite and fluorine-doped hydroxyapatite, are prepared by precipitating them in the alkaline medium in the presence of the protein component.
- the calcium salts (at least partially) also have rod-shaped structures, a numerically large amount of crystals having a length-to-breadth ratio of 1 to 2 resulting on account of the likewise overlapping length and breadth values of the calcium salt crystals prepared using this method.
- the crystals are deposited on the surface of the high molecular weight protein component employed, as a result of which they represent the spatial structure of the protein component to a certain extent.
- These composite materials can be used for “biomineralization” (mineral crystallization in a protein matrix), i.e. protein and calcium salt crystals are incorporated into the protein matrix of the teeth or bone. Consequently, the 3-dimensional structure of the composite materials is applied to the previous (tooth) surface, while, as mentioned above, hydroxyapatite crystals form laminar, 2-dimensional layers on the (tooth) surface.
- the biomineralization process is comparatively slow and leads to composite materials applied to the (tooth) surface whose mechanical properties can differ considerably from those of the pure crystals.
- WO 98/18719 describes a process for the lengthening of rod-shaped hydroxyapatite crystals in suspensions and the adjustment or concentration of the solids content of hydroxyapatite crystals in these suspensions.
- the original crystal length of 0.05 to 0.1 ⁇ m can be increased to 0.1 to 0.5 ⁇ m with constant breadth of 0.01 to 0.02 ⁇ m
- a solids content of 7 to 96% of hydroxyapatite crystals can be established in the suspension.
- the process is complicated; moreover, it is exclusively restricted to suspensions of hydroxyapatite crystals.
- the crystal length moreover also appears to be dependent on the solids content in the suspension.
- the object underlying the invention consists in the provision of rod-shaped apatite crystals which have an improved length-to-breadth ratio compared with the prior art, and in which the ratio of hydroxide ions to fluoride ions based on the total amount of the crystals can be simply varied. At the same time, suspensions of the rod-shaped apatite crystals having a variable solids content should also be provided.
- the object is achieved by a process for the preparation of dispersions which contain the rod-shaped apatite crystals described beforehand.
- the process according to the invention contains the following steps:
- step b) at least one fluoride-containing compound is added to the mixture present as a dispersion situated in the autoclave and mixed with this dispersion over a period of time of at least 1 hour.
- the pure apatite crystals can be isolated from the dispersions thus obtained by subjecting the dispersions to drying, in particular spray drying, in an additional process step.
- the advantage of the solution according to the invention lies in the fact that a novel process is provided with which apatite crystals can be prepared which are exclusively rod-shaped. Moreover, the process is restricted not only to the preparation of hydroxyapatite crystals, but mixtures of rod-shaped hydroxyapatite crystals and rod-shaped fluoroapatite crystals or rod-shaped mixed crystals of hydroxyapatite and fluoroapatite can also be prepared.
- the rod-shaped apatite crystals prepared using the process according to the invention have a length-to-breadth ratio of >5. This means that the crystals have a length-to-breadth ratio of 5 in the “most unfavorable” case, whereas, however, there are also a significant number of crystals which have a length-to-breadth ratio of markedly greater than 5, for example 8 to 15. In most processes according to the prior art, however, as already mentioned beforehand, a numerically large amount of crystals having a length-to-breadth ratio of 1 to 2 is produced.
- a further advantage of the process according to the invention can be seen in the simple handling of the adjustment of the fluoride ion concentration.
- the hydroxyapatite crystals have already been produced in rod form
- a defined number of hydroxide ions can be replaced by fluoride ions in an ion-exchange process without the rod form of the crystals being modified in this process.
- the process according to the invention is suitably carried out in an autoclave, in particular a stirred autoclave.
- an autoclave in particular a stirred autoclave.
- other vessels or devices known to the person skilled in the art can also be used, which withstand the reaction conditions under elevated pressure.
- a mixture for example in the form of a suspension, is produced in the autoclave from the starting materials and water.
- Suitable starting materials are, as the calcium-containing component, calcium hydroxide and, as the phosphorus-containing component, phosphoric acid.
- additives such as calcium chloride, calcium nitrate (tetrahydrate), ammonium hydrogenphosphate or diammonium hydrogenphosphate can also be admixed to the reaction.
- Calcium hydroxide and phosphoric acid are particularly suitable, the latter is preferably employed in 85% strength by weight form.
- Water is understood in the process according to the invention as in particular meaning completely deionized water, optionally the water, however, can also have a high residual ion content, for example of hydroxide ions and/or protons.
- completely deionized water is introduced into the autoclave and calcium hydroxide is added to the autoclave with stirring at room temperature.
- the suspension thus obtained is warmed to 40 to 50° C. and the phosphoric acid, which is optionally diluted with completely deionized water, is allowed to run into the autoclave with stirring over a suitable period of time.
- a temperature of at least 100° C. and a pressure of >1 bar is generated in the interior of the autoclave, and these conditions are maintained for at least 1 hour, preferably 5 to 16 hours.
- the second process step is carried out at pressures between 1.5 and 6 bar, particularly preferably between 2 and 5 bar.
- Preferred temperature ranges are 105° C. to 150° C., and 110° C. to 130° C. are particularly preferred. If appropriate, temperature gradients can also be used, temperature changes also causing pressure changes.
- the conditions of the second process step are maintained for 10 to 14 hours with stirring. If appropriate, the second process step can also be carried out in less than 1 hour.
- dispersions which contain rod-shaped hydroxyapatite crystals and which are preferably homogeneous.
- the solids content of these dispersions is 5 to 70% by weight, preferably 10 to 40% by weight, particularly preferably 15 to 30% by weight, of hydroxyapatite crystals; if appropriate, the solids content can also be ⁇ 5% by weight.
- the hydroxyapatite crystals prepared in this way (nearly always) have a rod-shaped form, the length-to-breadth ratio of the (individual) crystals being ⁇ 5, but being >20 only in exceptional cases.
- a length-to-breadth ratio of 8 to 15 is preferred, particularly preferably of 9 to 12.
- rod-shaped hydroxyapatite crystals can be prepared which have a length of 0.1 to 0.2 ⁇ m and a breadth of 0.01 to 0.02 ⁇ m, in each case based on the individual crystals.
- the thickness (i.e. the 3rd dimension) of the crystals corresponds to their breadth. It is thus evident that the crystals prepared by the process according to the invention only have a length-to-breadth (or thickness) ratio of 5 in the “most unfavourable” case. This case occurs with a crystal length of 0.1 ⁇ m and a crystal breadth or thickness of 0.02 ⁇ m.
- the length-to-breadth ratio can, however, also be at most 20 (length: 0.2 ⁇ m; breadth: 0.01 ⁇ m).
- the length-to-breadth ratio of the individual crystals can be controlled by the parameters pressure, temperature and reaction time in the second process step.
- the rod-shaped hydroxyapatite crystals can also be isolated from the dispersion.
- the dispersant can be removed by simple evaporation, if appropriate with the aid of vacuum.
- the dispersion can also be subjected to freeze drying for the isolation of the apatite crystals.
- the rod-shaped hydroxyapatite crystals prepared using the process according to the invention are isolated from the dispersion by spray drying, and the device necessary for this and the carrying out of the spray drying are known to the person skilled in the art.
- the isolated hydroxyapatite crystals can be redispersed again in water without problems to give homogeneous dispersions.
- organic compounds such as water-soluble, lower alcohols and glycols, polyethylene glycols, glycerol and mixtures of the organic compounds mentioned beforehand with one another and/or with water as dispersant can also be used for the redispersion.
- a third process step (c) the hydroxide ions in the hydroxyapatite crystals prepared according to the invention can be (partially) replaced by fluoride ions.
- at least one fluoride-containing compound is added to the dispersion prepared in the second process step.
- Suitable fluoride-containing compounds are sodium fluoride, calcium fluoride, potassium fluoride and arnmonium fluoride, and sodium fluoride is preferably suitable.
- the mixture thus obtained is mixed over a period of time of at least one hour, preferably 10 to 14 hours. Preferably, it is stirred at room temperature, if appropriate higher temperature values and/or lower mixing times than 1 hour can also be used.
- the third process step is presumably based on an ion-exchange mechanism.
- fluoride-containing compounds or mixtures of fluoride-containing compounds which contain no calcium ions as cations or do not exclusively contain calcium ions
- the calcium ions of the rod-shaped apatite crystals can be partially substituted by the cations deriving from the fluoride-containing compound.
- those rod-shaped apatite crystals in which the calcium ions are partially replaced by the cations deriving from the fluoride-containing compounds should also be included by the formula Ca 5 (PO 4 ) 3 (OH) x F y .
- rod-shaped apatite crystals of the formula Ca 5 (PO 4 ) 3 (OH) x F y can be prepared in which the length-to-breadth ratio of the crystals is ⁇ 5, preferably 8 to 15, particularly preferably 9 to 12. It is furthermore preferred that the thickness of the crystals corresponds to their breadth.
- any desired values for y from 0 to 1 can be set; this is controlled by the amount of the fluoride-containing compounds added, the temperature values and the duration of the mixing process in the third process step.
- the rod-shaped apatite crystals of the formula Ca 5 (PO 4 ) 3 (OH) x F y contained in the dispersion can be surrounded by one or more surface-modifying agents.
- Surface-modifying agents are understood as meaning substances which adhere physically to the surface of the crystals, but do not react chemically with these.
- Surface-modifying agents are particularly to be understood as meaning dispersants; the latter are known to the person skilled in the art, for example, also under the terms emulsifiers, protective colloids, wetting agents or detergents. Suitable surface-modifying agents are described, for example, in WO 01/01930.
- antiallergics and/or antiinflammatory active compounds can be used as surface-modifying agents.
- the surface-modifying agents are applied to the surface of the rod-shaped apatite crystals following the process for the preparation of rod-shaped apatite crystals according to the invention by processes known to the person skilled in the art.
- the apatite crystals of the formula Ca 5 (PO 4 ) 3 (OH) x F y prepared using the process according to the invention are suitable in isolated form and/or in the form of dispersions for use as a remineralizing component for teeth and/or bone.
- the apatite crystals can be present both in cleansing and care formulations and in formulations for the treatment of tooth and bone defects. Tooth gels, toothpastes (or tooth creams), mouthwash (or mouth rinses) and chewing gum may be mentioned in particular.
- the apatite crystals according to the present invention are used as a constituent of formulations for the induction or promotion of the new growth of bone tissue and for the coating of implants.
- the hydroxyapatite obtained consisted of stalk-shaped crystals of prismatic cross-section with breadths and thicknesses of 0.01 to 0.02 ⁇ m and lengths of 0.1 to 0.2 ⁇ m.
- the specific surface area was 49.4 m 2 /g.
- Example 2 was carried out analogously to example 1. After the dispersion containing the hydroxyapatite had been cooled to room temperature, 0.168 kg of sodium fluoride was added to the autoclave and the dispersion was stirred at room temperature for a further 12 h.
- the suspension was then drawn off from the autoclave.
- the X-ray diffractogram of a dried sample showed that about 20 mol % of the hydroxide ions, based on the total amount of the crystals, had been replaced by fluoride ions.
- the form and the dimensions of the crystals have not changed compared with those of the crystals from example 1.
- the specific surface area was 49.4 m 2 /g.
- Example 2 was repeated with the difference that after 20 min the reaction contents were heated at 100° C. to 150° C. and the reaction time at this temperature was reduced to 4 h. The pressure under these conditions was 4.5 bar. After the dispersion containing the hydroxyapatite had been cooled to room temperature, 0.067 kg of sodium fluoride was added.
- the X-ray diffractogram of the dried sample showed that about 8 mol % of the hydroxide ions, based on the total amount of the crystals, had been replaced by fluoride ions.
- the specific surface area was 46.8 m 2 /g
- the Ca/P ratio was 1.65
- the shape and the dimensions of the crystals corresponded to those from example 1.
- a solids content of 21.3% was determined for the dispersion thus obtained after cooling.
- the X-ray diffractograms of the crystals which were isolated from the dispersion showed the diffraction reflections of hydroxyapatite.
- the hydroxyapatite had the form of irregular spheres having diameters of 0.4 to 5 ⁇ m.
Abstract
The rod-shaped apatite crystals of the formula Ca5(PO4)3(OH)xFy have the following features
a) the length-to-breadth ratio of the crystals is at least ≧5 and
b) x+y=1, where if x or y≠0 the total amount of the crystals is present as a mixture of individual hydroxyapatite crystals and fluoroapatite crystals and/or as mixed crystals, such that, based on the total amount of the crystals, (1−x)·100% of the hydroxide ions present if y=0 are replaced by fluoride ions.
The invention furthermore describes dispersions which contain such rod-shaped apatite crystals, and a process for the preparation of the dispersions or of the apatite crystals.
Description
- The invention relates to rod-shaped apatite crystals which have a length-to-breadth ratio of >5 and in which the ratio of hydroxide ions to fluoride ions based on the total amount of the crystals can be simply varied. Furthermore, the invention relates to dispersions which contain such rod-shaped apatite crystals, and to a process for the preparation of the dispersions or of the apatite crystals.
- The dental enamel, just like human bone, consists mainly of hydroxyapatite. Owing to mechanical stress on the teeth (e.g. when eating or else alternatively when brushing the teeth), fissures and channels result in the dental enamel, which expose pores in the interior of the tooth. Substances can rapidly penetrate into the interior of the tooth through these pores and irritate the dental nerve, as a result of which the teeth become sensitive to sweetness, heat or cold. Moreover, in the case of bacterial attack caries forms in the fissures or in the pores, which is known extensively as a very dangerous dental disease.
- This problem has been known for a relatively long time and accordingly there are innumerable toothpastes or tooth gels which treat the pore formation in different ways. Particulate dispersed calcium phosphate crystals (having diameters of >5 μm) are frequently employed as calcium and phosphate ion suppliers for the construction of hydroxyapatite, as a result of which the fissures and unevenness of the tooth surface should be made good again. Most frequently, however, fluoride-containing compounds such as calcium fluoride are employed, as the conversion of the hydroxyapatite of the dental enamel into the significantly harder fluoroapatite is promoted by fluoridation. Fluoroapatite is less susceptible to bacterial attack and attacks by proteins than pure hydroxyapatite. Consequently, the dental enamel is strengthened and smoothed by fluoroapatite and the pores in the interior of the tooth are better sealed. Furthermore, there are also toothpastes which already contain hydroxyapatite (crystals) and/or fluoroapatite (crystals). Generally, however, fluorides cannot be added in any desired great amount, since in free form they discolor the teeth from a certain concentration.
- It is furthermore known that flat, in particular rod-shaped, hydroxyapatite crystals adsorb better on the tooth surface and form a sheet structure by self-organization which can seal the fissures and pores over a wide area. Rod-shaped crystals therefore have a better adsorbability, since the underlying van-der-Waal's interactions are proportional to the (surface) area. After the application, a mineral protective film thereby forms rapidly on the teeth, which in the course of time becomes identical to dental enamel by means of slow dissolution in the oral cavity and adsorption of the fluoride-containing compounds likewise contained in the toothpastes, smooths the dental enamel and effectively seals the fissures and/or pores.
- A problem, however, is the provision of rod-shaped (hydroxy)apatite crystals which make possible an effective adsorption on the tooth surface on account of an improved length-to-breadth ratio. The processes known hitherto for the preparation of apatite crystals usually yield crystals of spherical and irregular shape having particle sizes of >5 μm. In the recent past, however, processes have been published with which, in addition to the irregular and spherical shapes, rod-shaped apatite crystals having particle sizes in the submicrometer range can also be produced.
- WO 00/37033 describes suspensions of only slightly water-soluble calcium phosphates, calcium fluorides and calcium fluorophosphates, and their use in dental care compositions. The calcium salts contained in the suspensions are prepared by precipitation in an alkaline medium, the calcium salts being obtained in the form of crystals (primary particles) having thicknesses (diameters) of 0.005 to 0.05 μm and lengths of 0.01 to 0.15 μm. In order to stabilize the suspensions, the precipitation of the calcium salts is carried out in the presence of agglomeration inhibitors, such as water-soluble surfactants or water-soluble polymeric protective colloids. In this manner, suspensions of hydroxyapatite crystals and fluorine-doped hydroxyapatite crystals can also be prepared. The calcium salt crystals prepared in this way in some cases have rod-shaped structures. Inherent in the method, however, is the disadvantage that on account of the overlapping length and breadth values of the crystals a numerically large amount of crystals is also produced whose length-to-breadth ratio is in the range from 1 to 2, i.e. these crystals have no pronounced rod form or only a slightly pronounced rod form.
- In WO 01/01930, composite materials are described which comprise calcium salts which are poorly soluble in water, such as calcium phosphates and calcium fluorophosphates, and a protein component. The calcium salts, which also include hydroxyapatite, fluoroapatite and fluorine-doped hydroxyapatite, are prepared by precipitating them in the alkaline medium in the presence of the protein component. Optionally, the calcium salts (at least partially) also have rod-shaped structures, a numerically large amount of crystals having a length-to-breadth ratio of 1 to 2 resulting on account of the likewise overlapping length and breadth values of the calcium salt crystals prepared using this method. The crystals are deposited on the surface of the high molecular weight protein component employed, as a result of which they represent the spatial structure of the protein component to a certain extent. These composite materials can be used for “biomineralization” (mineral crystallization in a protein matrix), i.e. protein and calcium salt crystals are incorporated into the protein matrix of the teeth or bone. Consequently, the 3-dimensional structure of the composite materials is applied to the previous (tooth) surface, while, as mentioned above, hydroxyapatite crystals form laminar, 2-dimensional layers on the (tooth) surface. The biomineralization process, however, is comparatively slow and leads to composite materials applied to the (tooth) surface whose mechanical properties can differ considerably from those of the pure crystals.
- WO 98/18719 describes a process for the lengthening of rod-shaped hydroxyapatite crystals in suspensions and the adjustment or concentration of the solids content of hydroxyapatite crystals in these suspensions. By means of alternate stirring and filtering off at defined time intervals and using defined stirrer speeds, on the one hand the original crystal length of 0.05 to 0.1 μm can be increased to 0.1 to 0.5 μm with constant breadth of 0.01 to 0.02 μm, on the other hand a solids content of 7 to 96% of hydroxyapatite crystals can be established in the suspension. As a result of the numerous stirring and filtering steps, the process is complicated; moreover, it is exclusively restricted to suspensions of hydroxyapatite crystals. The crystal length moreover also appears to be dependent on the solids content in the suspension.
- The object underlying the invention consists in the provision of rod-shaped apatite crystals which have an improved length-to-breadth ratio compared with the prior art, and in which the ratio of hydroxide ions to fluoride ions based on the total amount of the crystals can be simply varied. At the same time, suspensions of the rod-shaped apatite crystals having a variable solids content should also be provided.
- The object is achieved by a process for the preparation of dispersions which contain the rod-shaped apatite crystals described beforehand. The process according to the invention contains the following steps:
- a) in an autoclave, a mixture is produced which contains the starting materials and water,
- b) a temperature of at least 100° C. and a pressure of >1 bar is generated in the interior of the autoclave and these conditions are maintained for at least 1 hour,
- c) if appropriate, following step b), at least one fluoride-containing compound is added to the mixture present as a dispersion situated in the autoclave and mixed with this dispersion over a period of time of at least 1 hour.
- The pure apatite crystals can be isolated from the dispersions thus obtained by subjecting the dispersions to drying, in particular spray drying, in an additional process step.
- The advantage of the solution according to the invention lies in the fact that a novel process is provided with which apatite crystals can be prepared which are exclusively rod-shaped. Moreover, the process is restricted not only to the preparation of hydroxyapatite crystals, but mixtures of rod-shaped hydroxyapatite crystals and rod-shaped fluoroapatite crystals or rod-shaped mixed crystals of hydroxyapatite and fluoroapatite can also be prepared.
- The rod-shaped apatite crystals prepared using the process according to the invention have a length-to-breadth ratio of >5. This means that the crystals have a length-to-breadth ratio of 5 in the “most unfavorable” case, whereas, however, there are also a significant number of crystals which have a length-to-breadth ratio of markedly greater than 5, for example 8 to 15. In most processes according to the prior art, however, as already mentioned beforehand, a numerically large amount of crystals having a length-to-breadth ratio of 1 to 2 is produced.
- Since all apatite crystals have a length-to-breadth ratio of ≧5, the adsorption on the tooth surface and the self-organization associated therewith functions, with formation of laminar structures, significantly better than with apatite crystals which have an unfavorable length-to-breadth ratio, because the apatite crystals according to the invention can also be packed particularly tightly. This is also an advantage compared with that prior art in which the apatite crystals used there are applied to the surface of proteins and are incorporated into the tooth or bone material together with these in a biomineralization process. The crystals incorporated by this process cannot be packed so tightly on the tooth surface as those produced by the process according to the invention. Moreover, the preparation costs of these mixtures of proteins and apatite crystals are much higher than the preparation costs of the rod-shaped apatite crystals of the process according to the invention, in which no protein component is necessary.
- A further advantage of the process according to the invention can be seen in the simple handling of the adjustment of the fluoride ion concentration. In the first process section, the hydroxyapatite crystals have already been produced in rod form, in the second process section a defined number of hydroxide ions can be replaced by fluoride ions in an ion-exchange process without the rod form of the crystals being modified in this process. By means of this process, in which both pure fluoroapatite crystals and mixed crystals of fluoroapatite and hydroxyapatite are produced, a total amount of apatite crystals is prepared which contains a defined, freely adjustable amount of fluoride ions. This is particularly of importance in the use of the apatite crystals, since the apatite crystals applied to the tooth surface for the sealing of holes or fissures form a mineral protective film, which solidifies more rapidly due to the incorporation of fluoride ions and thus also becomes identical to dental enamel more rapidly. As a result, the pores and fissures on the tooth surface are particularly effectively and rapidly sealed, and the danger of the formation of caries no longer exists at these sites.
- The process according to the invention is suitably carried out in an autoclave, in particular a stirred autoclave. Furthermore, other vessels or devices known to the person skilled in the art can also be used, which withstand the reaction conditions under elevated pressure.
- In the first step (a) of the process according to the invention, a mixture, for example in the form of a suspension, is produced in the autoclave from the starting materials and water.
- Suitable starting materials are, as the calcium-containing component, calcium hydroxide and, as the phosphorus-containing component, phosphoric acid. Optionally, additives such as calcium chloride, calcium nitrate (tetrahydrate), ammonium hydrogenphosphate or diammonium hydrogenphosphate can also be admixed to the reaction. Calcium hydroxide and phosphoric acid are particularly suitable, the latter is preferably employed in 85% strength by weight form. Water is understood in the process according to the invention as in particular meaning completely deionized water, optionally the water, however, can also have a high residual ion content, for example of hydroxide ions and/or protons.
- In a preferred embodiment of the process according to the invention, completely deionized water is introduced into the autoclave and calcium hydroxide is added to the autoclave with stirring at room temperature. The suspension thus obtained is warmed to 40 to 50° C. and the phosphoric acid, which is optionally diluted with completely deionized water, is allowed to run into the autoclave with stirring over a suitable period of time.
- In the second step (b) of the process according to the invention, which can also be regarded as a hydrothermal process, a temperature of at least 100° C. and a pressure of >1 bar is generated in the interior of the autoclave, and these conditions are maintained for at least 1 hour, preferably 5 to 16 hours. Preferably, the second process step is carried out at pressures between 1.5 and 6 bar, particularly preferably between 2 and 5 bar. Preferred temperature ranges are 105° C. to 150° C., and 110° C. to 130° C. are particularly preferred. If appropriate, temperature gradients can also be used, temperature changes also causing pressure changes. In a particularly preferred embodiment of the process according to the invention, the conditions of the second process step are maintained for 10 to 14 hours with stirring. If appropriate, the second process step can also be carried out in less than 1 hour.
- By means of the second process step, dispersions are obtained which contain rod-shaped hydroxyapatite crystals and which are preferably homogeneous. The solids content of these dispersions is 5 to 70% by weight, preferably 10 to 40% by weight, particularly preferably 15 to 30% by weight, of hydroxyapatite crystals; if appropriate, the solids content can also be <5% by weight. The hydroxyapatite crystals prepared in this way (nearly always) have a rod-shaped form, the length-to-breadth ratio of the (individual) crystals being ≧5, but being >20 only in exceptional cases. A length-to-breadth ratio of 8 to 15 is preferred, particularly preferably of 9 to 12. In particular, rod-shaped hydroxyapatite crystals can be prepared which have a length of 0.1 to 0.2 μm and a breadth of 0.01 to 0.02 μm, in each case based on the individual crystals. In a furthermore preferred embodiment, the thickness (i.e. the 3rd dimension) of the crystals corresponds to their breadth. It is thus evident that the crystals prepared by the process according to the invention only have a length-to-breadth (or thickness) ratio of 5 in the “most unfavourable” case. This case occurs with a crystal length of 0.1 μm and a crystal breadth or thickness of 0.02 μm. The length-to-breadth ratio can, however, also be at most 20 (length: 0.2 μm; breadth: 0.01 μm). The length-to-breadth ratio of the individual crystals can be controlled by the parameters pressure, temperature and reaction time in the second process step.
- The rod-shaped hydroxyapatite crystals can also be isolated from the dispersion. The dispersant can be removed by simple evaporation, if appropriate with the aid of vacuum. Furthermore, the dispersion can also be subjected to freeze drying for the isolation of the apatite crystals. Preferably, the rod-shaped hydroxyapatite crystals prepared using the process according to the invention are isolated from the dispersion by spray drying, and the device necessary for this and the carrying out of the spray drying are known to the person skilled in the art. The isolated hydroxyapatite crystals can be redispersed again in water without problems to give homogeneous dispersions. If appropriate, instead of water, organic compounds such as water-soluble, lower alcohols and glycols, polyethylene glycols, glycerol and mixtures of the organic compounds mentioned beforehand with one another and/or with water as dispersant can also be used for the redispersion.
- In a third process step (c), the hydroxide ions in the hydroxyapatite crystals prepared according to the invention can be (partially) replaced by fluoride ions. For this, at least one fluoride-containing compound is added to the dispersion prepared in the second process step. Suitable fluoride-containing compounds are sodium fluoride, calcium fluoride, potassium fluoride and arnmonium fluoride, and sodium fluoride is preferably suitable. The mixture thus obtained is mixed over a period of time of at least one hour, preferably 10 to 14 hours. Preferably, it is stirred at room temperature, if appropriate higher temperature values and/or lower mixing times than 1 hour can also be used. The third process step is presumably based on an ion-exchange mechanism.
- On the basis of the additional third process step, dispersions according to the invention comprising rod-shaped apatite crystals of the formula Ca5(PO4)3(OH)xFy can be prepared, where x+y=1. If x or y≠0, the total amount of the crystals is present as a mixture of individual hydroxyapatite crystals and fluoroapatite crystals (i.e. in the crystal the hydroxide ions have been completely replaced by fluoride ions) and/or as mixed crystals of fluoroapatite and hydroxyapatite, where, based on the total amount of the crystals, (1−x)·100% of the hydroxide ions present if y=0 are replaced by fluoride ions.
- Provided in the third process step fluoride-containing compounds or mixtures of fluoride-containing compounds are employed which contain no calcium ions as cations or do not exclusively contain calcium ions, the calcium ions of the rod-shaped apatite crystals can be partially substituted by the cations deriving from the fluoride-containing compound. In the following text, those rod-shaped apatite crystals in which the calcium ions are partially replaced by the cations deriving from the fluoride-containing compounds should also be included by the formula Ca5(PO4)3(OH)xFy.
- As a result of the replacement of the hydroxide ions by fluoride ions and, if appropriate, as a result of the partial calcium ion replacement, neither the form or size of the apatite crystals nor the solids content in the dispersion have changed, i.e. the details given with respect to this for the hydroxyapatite crystals (x=1) also apply for the apatite crystals of the formula Ca5(PO4)3(OH)xFy. It may again be expressly mentioned that by means of the process according to the invention rod-shaped apatite crystals of the formula Ca5(PO4)3(OH)xFy can be prepared in which the length-to-breadth ratio of the crystals is ≧5, preferably 8 to 15, particularly preferably 9 to 12. It is furthermore preferred that the thickness of the crystals corresponds to their breadth.
- Any desired values for y from 0 to 1 can be set; this is controlled by the amount of the fluoride-containing compounds added, the temperature values and the duration of the mixing process in the third process step. Preferably, rod-shaped apatite crystals are prepared in which, based on the total amount of the crystals, 0.01 to 30%, particularly preferably 0.5 to 20%, of the hydroxide ions present if y=0 are replaced by fluoride ions. The rod-shaped apatite crystals of the formula Ca5(PO4)3(OH)xFy are isolated from the dispersion analogously to the details for the case where x=1 (hydroxyapatite crystals).
- In a further embodiment of the present invention, the rod-shaped apatite crystals of the formula Ca5(PO4)3(OH)xFy contained in the dispersion can be surrounded by one or more surface-modifying agents. Surface-modifying agents are understood as meaning substances which adhere physically to the surface of the crystals, but do not react chemically with these. Surface-modifying agents are particularly to be understood as meaning dispersants; the latter are known to the person skilled in the art, for example, also under the terms emulsifiers, protective colloids, wetting agents or detergents. Suitable surface-modifying agents are described, for example, in WO 01/01930. Furthermore, antiallergics and/or antiinflammatory active compounds can be used as surface-modifying agents. The surface-modifying agents are applied to the surface of the rod-shaped apatite crystals following the process for the preparation of rod-shaped apatite crystals according to the invention by processes known to the person skilled in the art.
- The apatite crystals of the formula Ca5(PO4)3(OH)xFy prepared using the process according to the invention are suitable in isolated form and/or in the form of dispersions for use as a remineralizing component for teeth and/or bone. The apatite crystals can be present both in cleansing and care formulations and in formulations for the treatment of tooth and bone defects. Tooth gels, toothpastes (or tooth creams), mouthwash (or mouth rinses) and chewing gum may be mentioned in particular. Furthermore, the apatite crystals according to the present invention are used as a constituent of formulations for the induction or promotion of the new growth of bone tissue and for the coating of implants.
- The invention is additionally illustrated with the aid of the following examples.
- 16.0 kg of completely deionized water were introduced into a (stirred) autoclave of volume 55 1. 5.925 kg of calcium hydroxide (Schäfer white lime hydrate, Precal 54) were added in while stirring with an anchor stirrer at 90 revolutions per minute (rpm) and the suspension resulting therefrom was heated to 45° C.
- 5.534 kg of 85% strength phosphoric acid, which was diluted with 10.390 kg of completely deionized water, were allowed to run in at this temperature over the course of 120 min.
- The autoclave was then sealed and the temperature was raised to 100° C. After stirring at 100° C. for 20 min, the temperature was raised to 120° C., whereupon a pressure of 2.3 bar was established.
- The mixture was stirred under these conditions for 12 h, then cooled to room temperature.
- After cooling, a solids content of 21.6% and a Ca/P ratio of 1.69 was determined for the dispersion thus obtained. A sample of the dispersion was taken, from which the dispersing agent was then removed by drying at 120° C. and about 10 mbar. The dried crystals showed the diffraction reflections of pure hydroxyapatite in the X-ray diffractogram.
- The hydroxyapatite obtained consisted of stalk-shaped crystals of prismatic cross-section with breadths and thicknesses of 0.01 to 0.02 μm and lengths of 0.1 to 0.2 μm. The specific surface area was 49.4 m2/g.
- Example 2 was carried out analogously to example 1. After the dispersion containing the hydroxyapatite had been cooled to room temperature, 0.168 kg of sodium fluoride was added to the autoclave and the dispersion was stirred at room temperature for a further 12 h.
- The suspension was then drawn off from the autoclave. The X-ray diffractogram of a dried sample showed that about 20 mol % of the hydroxide ions, based on the total amount of the crystals, had been replaced by fluoride ions. The form and the dimensions of the crystals have not changed compared with those of the crystals from example 1. The specific surface area was 49.4 m2/g.
- Example 2 was repeated with the difference that after 20 min the reaction contents were heated at 100° C. to 150° C. and the reaction time at this temperature was reduced to 4 h. The pressure under these conditions was 4.5 bar. After the dispersion containing the hydroxyapatite had been cooled to room temperature, 0.067 kg of sodium fluoride was added.
- The X-ray diffractogram of the dried sample showed that about 8 mol % of the hydroxide ions, based on the total amount of the crystals, had been replaced by fluoride ions. The specific surface area was 46.8 m2/g, the Ca/P ratio was 1.65, and the shape and the dimensions of the crystals corresponded to those from example 1.
- 16.0 kg of completely deionized water were introduced into a stirred container of volume 55 1 and 5.925 kg of calcium hydroxide (Schäfer white lime hydrate, Precal 54) were added in while stirring with an anchor stirrer at 90 rpm and the suspension resulting therefrom was heated to 70° C.
- 5.534 kg of 85% strength phosphoric acid, which was diluted with 10.39 kg of completely deionized water, were allowed to run in at this temperature over the course of 30 min while cooling and keeping the temperature constant. The reaction mixture was stirred at 70° C. for a further 2 h and then cooled to room temperature.
- A solids content of 21.3% was determined for the dispersion thus obtained after cooling. The X-ray diffractograms of the crystals which were isolated from the dispersion showed the diffraction reflections of hydroxyapatite. The hydroxyapatite had the form of irregular spheres having diameters of 0.4 to 5 μm.
Claims (13)
1. A rod-shaped apatite crystal of the formula Ca5(PO4)3(OH)xFy, wherein
a) the length-to-breadth ratio of the crystals is at least ≧5 and
b) x+y=1, where if x or y≠0 the total amount of the crystals is present as a mixture of individual hydroxyapatite crystals and fluoroapatite crystals and/or as mixed crystals, such that, based on the total amount of the crystals, (1−x) 100% of the hydroxide ions present if y=0 are replaced by fluoride ions.
2. A rod-shaped apatite crystal as claimed in claim 1 , wherein if y≠0 the calcium ions are partially substituted by other cations, in particular sodium, potassium and/or ammonium ions.
3. A rod-shaped apatite crystal as claimed in claim 1 or 2, wherein the length-to-breadth ratio of the crystals is 5 to 20, preferably 8 to 15, particularly preferably 9 to 12.
4. A rod-shaped apatite crystal as claimed in one of claims 1 to 3 , wherein, based on the total amount of the crystals, 0.01 to 30%, in particular 0.5 to 20%, of the hydroxide ions present if y=0 are replaced by fluoride ions.
5. A rod-shaped apatite crystal as claimed in one of claims 1 to 4 , wherein the thickness of the individual crystals corresponds approximately to their breadth.
6. A rod-shaped apatite crystal as claimed in one of claims 1 to 5 , wherein the thickness and the breadth are 0.01 to 0.02 μm and the length of the crystals is 0.1 to 0.2 μm.
7. A dispersion comprising rod-shaped apatite crystals as claimed in one of claims 1 to 6 , wherein the solids content of apatite crystals is 5 to 70% by weight, preferably 10 to 40% by weight, particularly preferably 15 to 30% by weight.
8. A process for the preparation of dispersions as claimed in claim 7 , which comprises
a) producing, in an autoclave, a mixture which contains the starting materials and water,
b) generating a temperature of at least 100° C. and a pressure of >1 bar in the interior of the autoclave and maintaining these conditions for at least 1 hour,
c) if appropriate, following step b), adding at least one fluoride-containing compound to the mixture present as a dispersion situated in the autoclave and mixing with this dispersion over a period of time of at least 1 hour.
9. A process as claimed in claim 8 , wherein the starting materials used are calcium hydroxide and phosphoric acid.
10. A process as claimed in claim 8 or 9, wherein the fluoride-containing compound is sodium fluoride, calcium fluoride, potassium fluoride and/or ammonium fluoride.
11. A process as claimed in one of claims 8 to 10 , wherein a pressure of between 1.5 and 6 bar, in particular between 2 and 5 bar, is generated in the interior of the autoclave.
12. A process for the preparation of rod-shaped apatite crystals as claimed in one of claims 1 to 6 , wherein a dispersion is prepared by the process as claimed in one of claims 8 to 11 and the rod-shaped apatite crystals are then isolated from the dispersion by spray drying.
13. The use of rod-shaped apatite crystals as claimed in one of claims 1 to 6 and/or of dispersions as claimed in claim 7 as a remineralizing component for teeth and/or bone in cleansing and care formulations, and formulations for the treatment of tooth and bone defects, in particular in tooth gel, toothpaste, mouthwash and chewing gum, in formulations for the induction or promotion of the new growth of bone tissue and for the coating of implants.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/169,681 US7153482B2 (en) | 2001-06-22 | 2005-06-30 | Rod shaped apatite crystals having a specific length-to-width ratio |
US11/557,291 US7320728B2 (en) | 2001-06-22 | 2006-11-07 | Rod-shaped apatite crystals having a specific length-to-width ratio |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10130121.9 | 2001-06-22 | ||
DE10130121A DE10130121A1 (en) | 2001-06-22 | 2001-06-22 | Rod-shaped apatite crystals for use e.g. in remineralization of teeth or bones or in toothpastes have improved length:breadth ratio and variable hydroxide:fluoride ion ratio |
DE10133449A DE10133449A1 (en) | 2001-07-10 | 2001-07-10 | Rod-shaped apatite crystals for use e.g. in remineralization of teeth or bones or in toothpastes have improved length:breadth ratio and variable hydroxide:fluoride ion ratio |
DE10133449.4 | 2001-07-10 | ||
PCT/EP2002/006867 WO2003000588A1 (en) | 2001-06-22 | 2002-06-20 | Rod shaped apatite crystals with a specific length-to-width ratio |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/169,681 Continuation US7153482B2 (en) | 2001-06-22 | 2005-06-30 | Rod shaped apatite crystals having a specific length-to-width ratio |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040171471A1 true US20040171471A1 (en) | 2004-09-02 |
Family
ID=26009565
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/480,809 Abandoned US20040171471A1 (en) | 2001-06-22 | 2002-06-20 | Rod shaped apatite crystals with a specific length-to-width ratio |
US11/169,681 Expired - Fee Related US7153482B2 (en) | 2001-06-22 | 2005-06-30 | Rod shaped apatite crystals having a specific length-to-width ratio |
US11/557,291 Expired - Fee Related US7320728B2 (en) | 2001-06-22 | 2006-11-07 | Rod-shaped apatite crystals having a specific length-to-width ratio |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/169,681 Expired - Fee Related US7153482B2 (en) | 2001-06-22 | 2005-06-30 | Rod shaped apatite crystals having a specific length-to-width ratio |
US11/557,291 Expired - Fee Related US7320728B2 (en) | 2001-06-22 | 2006-11-07 | Rod-shaped apatite crystals having a specific length-to-width ratio |
Country Status (6)
Country | Link |
---|---|
US (3) | US20040171471A1 (en) |
EP (1) | EP1401762A1 (en) |
JP (1) | JP2004538228A (en) |
CN (1) | CN1250449C (en) |
CA (1) | CA2451554A1 (en) |
WO (1) | WO2003000588A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007065856A1 (en) * | 2005-12-05 | 2007-06-14 | Glaxo Group Limited | Oral compositions comprising rod-shaped apatite nanocrystals |
WO2008037252A1 (en) * | 2006-09-29 | 2008-04-03 | Gumlink A/S | Chewing gum comprising hvdroxyapatite |
US20170172854A1 (en) * | 2014-03-20 | 2017-06-22 | The Regents Of The University Of Michigan | Bioactive "smart" dental composite materials |
US10537658B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
US10537661B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2007006103A (en) | 2004-11-22 | 2007-07-20 | Vertex Pharma | Pyrrolopyrazines and pyrazolopyrazines useful as inhibitors of protein kinases. |
WO2011053598A1 (en) | 2009-10-26 | 2011-05-05 | Rutgers, The State University Of New Jersey | Hydroxyapatite with controllable size and morphology |
EP1846325A4 (en) * | 2005-01-04 | 2010-04-21 | Univ Rutgers | Hydroxyapatite with controllable size and morphology |
EP1762215A1 (en) * | 2005-09-13 | 2007-03-14 | Unilever N.V. | Oral care composition |
HUE034085T2 (en) * | 2006-05-30 | 2018-01-29 | Coswell Spa | Biologicallly active nanoparticles of a carbonate-substituted hydroxyapatite, process for their preparation and compositions incorporating the same |
ITFI20060139A1 (en) * | 2006-06-08 | 2007-12-09 | Colorobbia Italia | NANOMETRIC HYDROXYPATITIS, ITS SUSPENSIONS PREPARATION AND USE. |
FR2906331B1 (en) * | 2006-09-26 | 2009-07-10 | Antonov Automotive Europ | "COMPACT MULTI-REPORTING TRANSMISSION DEVICE" |
JP5458230B2 (en) * | 2007-08-30 | 2014-04-02 | HOYA Technosurgical株式会社 | Method for producing fluorapatite, fluorapatite and adsorption device |
US8765168B2 (en) | 2009-11-06 | 2014-07-01 | The Regents Of The University Of Michigan | Compositions of a fluorapatite and methods of use |
US8357732B2 (en) * | 2010-03-14 | 2013-01-22 | Mehdi Sadat-Shojai | Method for production of biocompatible nanoparticles containing dental adhesive |
US8715625B1 (en) | 2010-05-10 | 2014-05-06 | The Clorox Company | Natural oral care compositions |
EP3202914B2 (en) | 2011-08-31 | 2023-06-28 | The University of Manchester | Method for treating a neurodegenerative disease |
CN102805879B (en) * | 2012-07-20 | 2014-09-24 | 陈卓凡 | Preparation method for biogenic fluorinated porcine hydroxyapatite (FPHA) bone substitution material |
ES2565637T3 (en) * | 2013-09-30 | 2016-04-06 | Universidade De Vigo | Method of obtaining faceted fluorapatite nanocrystals |
KR101643336B1 (en) * | 2014-10-14 | 2016-07-27 | 서울대학교산학협력단 | Multi-ion co-substituted calcium phosphate ceramics with charged lattice defects and method for manufacturing the same |
RU2652193C1 (en) * | 2017-04-19 | 2018-04-25 | Федеральное государственное бюджетное учреждение науки Институт химии твердого тела Уральского отделения Российской академии наук | Method of preparing apatite suspension |
DE102019109143A1 (en) | 2019-04-08 | 2020-10-08 | Chemische Fabrik Budenheim Kg | Hydroxyapatite powder and process for its manufacture |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4794171A (en) * | 1985-09-23 | 1988-12-27 | Toa Nenryo Kogyo Kabushiki Kaisha | Calcium-phosphate type hydroxyapatite and process for producing same |
US5858318A (en) * | 1996-11-27 | 1999-01-12 | Luo; Ping | Methods of synthesizing hydroxyapatite powders and bulk materials |
US6013591A (en) * | 1997-01-16 | 2000-01-11 | Massachusetts Institute Of Technology | Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5645814A (en) * | 1979-09-25 | 1981-04-25 | Kureha Chem Ind Co Ltd | Hydroxyapatite, its ceramic material and its manufacture |
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 |
DE19930335A1 (en) | 1999-07-02 | 2001-01-18 | Henkel Kgaa | Composite materials made from calcium compounds and protein components |
DE19953771C1 (en) * | 1999-11-09 | 2001-06-13 | Coripharm Medizinprodukte Gmbh | Absorbable bone implant material and method for producing the same |
DE10027946A1 (en) * | 2000-06-08 | 2001-12-13 | Wolfgang Wiedemann | Dental ceramic used in dentistry as filling material and tooth replacement is anisotropic and contains a large amount of hydroxylapatite |
AU2000267174A1 (en) * | 2000-07-03 | 2002-01-14 | Zakrytoe Aktsionernoe Obschestvo "Ostim" | Method for producing nano-sized crystalline hydroxyapatite |
US6478825B1 (en) * | 2001-11-28 | 2002-11-12 | Osteotech, Inc. | Implant, method of making same and use of the implant for the treatment of bone defects |
-
2002
- 2002-06-20 US US10/480,809 patent/US20040171471A1/en not_active Abandoned
- 2002-06-20 JP JP2003506800A patent/JP2004538228A/en active Pending
- 2002-06-20 CA CA002451554A patent/CA2451554A1/en not_active Abandoned
- 2002-06-20 CN CNB028124537A patent/CN1250449C/en not_active Expired - Fee Related
- 2002-06-20 EP EP02745399A patent/EP1401762A1/en not_active Withdrawn
- 2002-06-20 WO PCT/EP2002/006867 patent/WO2003000588A1/en active Application Filing
-
2005
- 2005-06-30 US US11/169,681 patent/US7153482B2/en not_active Expired - Fee Related
-
2006
- 2006-11-07 US US11/557,291 patent/US7320728B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4794171A (en) * | 1985-09-23 | 1988-12-27 | Toa Nenryo Kogyo Kabushiki Kaisha | Calcium-phosphate type hydroxyapatite and process for producing same |
US5858318A (en) * | 1996-11-27 | 1999-01-12 | Luo; Ping | Methods of synthesizing hydroxyapatite powders and bulk materials |
US6013591A (en) * | 1997-01-16 | 2000-01-11 | Massachusetts Institute Of Technology | Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007065856A1 (en) * | 2005-12-05 | 2007-06-14 | Glaxo Group Limited | Oral compositions comprising rod-shaped apatite nanocrystals |
WO2008037252A1 (en) * | 2006-09-29 | 2008-04-03 | Gumlink A/S | Chewing gum comprising hvdroxyapatite |
US20090280070A1 (en) * | 2006-09-29 | 2009-11-12 | Gumlink A/S | Chewing gum comprising hydroxyapatite |
US20170172854A1 (en) * | 2014-03-20 | 2017-06-22 | The Regents Of The University Of Michigan | Bioactive "smart" dental composite materials |
US10130560B2 (en) * | 2014-03-20 | 2018-11-20 | The Regents Of The University Of Michigan | Bioactive “smart” dental composite materials |
US10537658B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
US10537661B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
US11058799B2 (en) | 2017-03-28 | 2021-07-13 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
US11141505B2 (en) | 2017-03-28 | 2021-10-12 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
US11793907B2 (en) | 2017-03-28 | 2023-10-24 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
US11793910B2 (en) | 2017-03-28 | 2023-10-24 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
Also Published As
Publication number | Publication date |
---|---|
US7153482B2 (en) | 2006-12-26 |
US7320728B2 (en) | 2008-01-22 |
JP2004538228A (en) | 2004-12-24 |
US20070065355A1 (en) | 2007-03-22 |
WO2003000588A1 (en) | 2003-01-03 |
CN1250449C (en) | 2006-04-12 |
EP1401762A1 (en) | 2004-03-31 |
CA2451554A1 (en) | 2003-01-03 |
US20050238557A1 (en) | 2005-10-27 |
CN1518522A (en) | 2004-08-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7153482B2 (en) | Rod shaped apatite crystals having a specific length-to-width ratio | |
AU2013217399B2 (en) | Multicomponent oral care composition | |
KR101258976B1 (en) | Biologically active nanoparticles of a carbonate-substituted hydroxyapatite, process for their preparation and compositions incorporating the same | |
US9320692B2 (en) | Tooth fluoridating and remineralizing compositions and methods, based on nanoaggregate formation | |
AU2006238688B2 (en) | Oral hygiene compositions | |
WO2006030782A1 (en) | Ceramic particle group and method for production thereof and use thereof | |
DE10028975B4 (en) | Compositions for the treatment of tooth and / or bone tissue | |
EP1098623A2 (en) | Odontostomatologic use of apatite-based nanostructured materials | |
KR20120022781A (en) | Tooth surface repairing material | |
US20220296477A1 (en) | Stabilized amorphous calcium magnesium phosphate particle compositions | |
EA035044B1 (en) | Device for delivering an enamel regeneration system to the surfaces of teeth | |
JP3836703B2 (en) | Dentifrice | |
DE10130121A1 (en) | Rod-shaped apatite crystals for use e.g. in remineralization of teeth or bones or in toothpastes have improved length:breadth ratio and variable hydroxide:fluoride ion ratio | |
JPH1081514A (en) | Calcium carbonate-calcium phosphate-based composite | |
WO2020212159A1 (en) | Oral care product | |
RO133124B1 (en) | Nano materials based on multi-substituted hydroxyapatite and process for preparing the same | |
JPH10175833A (en) | Dental polishing and repairing agent and dentifrice | |
DE10133449A1 (en) | Rod-shaped apatite crystals for use e.g. in remineralization of teeth or bones or in toothpastes have improved length:breadth ratio and variable hydroxide:fluoride ion ratio | |
JPH0351051A (en) | Bone defect section and bone void section filler | |
MXPA02001269A (en) | Composition for restoring defects in calcified tissues |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: BASF AKTIENGESELLSCHAFT, GERMANY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NOERENBERG, RALF;STERZEL, HANS-JOSEF;KOCH, VOLKER;REEL/FRAME:015175/0484;SIGNING DATES FROM 20030202 TO 20030902 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |