CN1785442A - Preparation method of non-sizing nano-calcium phosphate powder for medical slow release metal ion - Google Patents
Preparation method of non-sizing nano-calcium phosphate powder for medical slow release metal ion Download PDFInfo
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- CN1785442A CN1785442A CN 200510061751 CN200510061751A CN1785442A CN 1785442 A CN1785442 A CN 1785442A CN 200510061751 CN200510061751 CN 200510061751 CN 200510061751 A CN200510061751 A CN 200510061751A CN 1785442 A CN1785442 A CN 1785442A
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- solution
- calcium phosphate
- metal ion
- calcium
- preparation
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- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 31
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 31
- 239000000843 powder Substances 0.000 title claims description 22
- 229910021645 metal ion Inorganic materials 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title claims description 14
- 238000004513 sizing Methods 0.000 title claims description 12
- 239000011575 calcium Substances 0.000 claims abstract description 48
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 229920000642 polymer Polymers 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 97
- 239000002202 Polyethylene glycol Substances 0.000 claims description 27
- 229920001223 polyethylene glycol Polymers 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 20
- 239000011574 phosphorus Substances 0.000 claims description 20
- 229910052698 phosphorus Inorganic materials 0.000 claims description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- 239000011701 zinc Substances 0.000 claims description 17
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 229910052791 calcium Inorganic materials 0.000 claims description 11
- 239000011777 magnesium Substances 0.000 claims description 11
- 238000004108 freeze drying Methods 0.000 claims description 10
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 238000010276 construction Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 229920002125 Sokalan® Polymers 0.000 claims description 7
- 239000011572 manganese Substances 0.000 claims description 7
- 239000004584 polyacrylic acid Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 239000012670 alkaline solution Substances 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 229910052691 Erbium Inorganic materials 0.000 claims description 4
- 229910052693 Europium Inorganic materials 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 229910052712 strontium Inorganic materials 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 229910052726 zirconium Inorganic materials 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 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 description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 2
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- 230000000536 complexating effect Effects 0.000 claims description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 2
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 claims description 2
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 229910052746 lanthanum Inorganic materials 0.000 claims description 2
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- 229910001414 potassium ion Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 abstract description 10
- 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 abstract description 10
- 210000000988 bone and bone Anatomy 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000010261 cell growth Effects 0.000 abstract description 2
- 150000001455 metallic ions Chemical class 0.000 abstract 3
- 239000002105 nanoparticle Substances 0.000 abstract 1
- 230000004952 protein activity Effects 0.000 abstract 1
- 239000003381 stabilizer Substances 0.000 abstract 1
- 229960001714 calcium phosphate Drugs 0.000 description 22
- 239000012153 distilled water Substances 0.000 description 21
- 239000002245 particle Substances 0.000 description 10
- 229960005069 calcium Drugs 0.000 description 9
- 238000001914 filtration Methods 0.000 description 8
- 238000013019 agitation Methods 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000004321 preservation Methods 0.000 description 7
- 230000006641 stabilisation Effects 0.000 description 7
- 238000011105 stabilization Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 210000004409 osteocyte Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 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 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Inorganic materials [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
An amorphous calcium phosphate nano-particle to slowly release metallic ions for medical purpose is prepared from the compound containing metallic ions, the compound containing P, the compound containing Ca and the polymer as stabilizer through reaction at 0-20 deg.C. Its advantage is high effect to promote protein activity and the growth of cells and bone, and control the release rate of metallic ions.
Description
Technical field
The present invention relates to a kind of preparation method, particularly a kind of low particle size as biological bone reparation or substitution material, the preparation method of the non-sizing nano-calcium phosphate powder of controllable sustained-release metal ion.
Background technology
Calcium phosphate material because of its have with skeleton in inorganic mutually similar chemical composition, and be widely used as the skeleton substitution material.Amorphous calcium phosphate and is widely used in biomedical sectors such as biological coating, bone cement because it has than crystalline calcium phosphate superior bioactive and biodegradability more, more and more is subjected to the attention of researcher.Amorphous calcium phosphate is a kind of intermediate product that exists when preparing hydroxyapatite in aqueous solution, is easy to change into crystalline calcium phosphate.All the time, researcher attempts to find a kind of method more easily to obtain amorphous calcium phosphate in aqueous solution.People such as Antonucci (Polymeric amorphous calciumphosphate compositions, Antomucci, et al.US5683461).But this method is introduced plurality of impurities easily, but also is reactionlessness.The bio-medical non-sizing nano-calcium phosphate that Chinese patent CN1488574 makes is as bioactive materials, can not fine stimulatory protein(SP) activity after implanting, and promote the growth of bone or suppress the absorption of bone, thereby limited its further application.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of non-sizing nano-calcium phosphate powder of medical slow release metal ion.
The method of the non-sizing nano-calcium phosphate powder of preparation medical slow release metal ion provided by the invention, employing be coprecipitation, may further comprise the steps:
1) calcium containing compound is soluble in water, being mixed with concentration is the A solution of 0.1～5mol/L, places under 0～20 ℃; The metal ion chemical compound is soluble in water, and being mixed with concentration is the B solution of 0.01～1.0mol/L, places under 0～20 ℃; Phosphorus-containing compound is soluble in water, be mixed with the solution that concentration is 0.1～5mol/L, place under 0～20 ℃;
2) a certain proportion of A solution and B solution are mixed formation C solution, wherein the mol ratio of M/ (M+Ca) is 0.0001～0.1, and M represents one or more in Zn, Sr, Mg, La, Eu, Er, Mn, Si, Zr, Na, the K ion;
3) an amount of polymer is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the addition of polymer is, the mol ratio of polymer and calcium ion is 1: 10～10: 1, and polymer calculates with the molal quantity of construction unit;
4) be 1.00～2.00 by the Ca/P mol ratio, the phosphorus-containing compound drips of solution is added in the D solution, drip alkaline solution during reaction and regulate pH value 7～12, be reflected at constantly and carry out under the stirring, reaction temperature is 0 ℃～5 ℃, after reaction finished, separation, washing, lyophilization obtained the amorphous nano-calcium phosphate powder of containing metal.
Among the present invention, described calcium containing compound can be lime nitrate or calcium chloride or calcium hydroxide.The containing metal chemical compound is to contain soluble compounds such as the nitrate of zinc, strontium, magnesium, lanthanum, europium, erbium, manganese, silicon, zirconium, sodium, potassium ion or chloride.Phosphorus-containing compound can be ammonium hydrogen phosphate or sodium phosphate or phosphoric acid or potassium phosphate.Polymer has the functional group that can produce complexing with metal cation, is selected from Polyethylene Glycol or polyacrylic acid.The alkaline solution that is used to regulate pH value can adopt ammonia or sodium hydroxide or potassium hydroxide solution, and the speed that drips alkaline solution is generally 1～20ml/min.
In the preparation process of the present invention, adopt methods such as sucking filtration or centrifugalize to separate, drying can adopt lyophilization.
The slow release metal ion amorphous calcium phosphate particles of powder size that the present invention makes is little, is nanoscale, and its particle diameter is evenly distributed between 10nm～50nm, does not reunite, and easily disperses, and is active high.With slow release metal ion amorphous calcium phosphate powder of the present invention and Organic substance such as collagen, polylactic acid is compound, can obtain ideal microstructure and performance.Slow release metal ion is a trace element necessary in the human body in physiological environment, and effectively the stimulatory protein(SP) activity promotes cell growth and osteogenesis.Can activate multiple protein such as zinc, stimulation of bone growth, and suppress the ability of bone resorption in addition; Magnesium is promote osteogenesis, safeguards the important minerals of osteocyte structure and function; The differentiation of manganese and osteocyte, collagen protein and mucopolysaccharide synthetic etc. all have relation; Recently regulate its metal ion content by the mole of regulating M/ (M+Ca), reach controlled metal ion rate of release.The coprecipitation preparation process condition that the present invention adopts is simple, simple to operate, and cost is low, is easy to industrialization.
The specific embodiment
Embodiment 1
With Ca (NO
3)
26H
2O is dissolved in the distilled water that to form calcium concentration be the A solution of 0.1mol/L, places under 0～20 ℃; With Zn (NO
3)
24H
2O is dissolved in the distilled water that to form metal concentration be the B solution of 1.0mol/L, places under 0～20 ℃; (NH
4)
2HPO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 0.1mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by Zn/ (Zn+Ca) mol ratio of design; An amount of Polyethylene Glycol (PEG) is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of PEG and Ca is PEG: Ca (NO
3)
2=3: 1, Polyethylene Glycol calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of Zn, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 2
With Ca (OH)
2Be dissolved in the distilled water that to form calcium concentration be the A solution of 5mol/L, place under 0～20 ℃; With Sr (NO
3)
2Be dissolved in the distilled water that to form metal concentration be the B solution of 0.01mol/L, place under 0～20 ℃; Na
3PO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 0.1mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by Sr/ (Sr+Ca) mol ratio of design; An amount of polyacrylic acid is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of polyacrylic acid and Ca is 3: 1, and polyacrylic acid calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of Sr, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 3
With CaCl
2Be dissolved in the distilled water that to form calcium concentration be the A solution of 5mol/L, place under 0～20 ℃; With Mg (NO
3)
2Be dissolved in the distilled water that to form metal concentration be the B solution of 1.0mol/L, place under 0～20 ℃; K
3PO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 0.1mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by Mg/ (Mg+Ca) mol ratio of design; An amount of Polyethylene Glycol (PEG) is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of PEG and Ca is PEG: CaCl
2=3: 1, Polyethylene Glycol calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of Mg, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 4
With Ca (NO
3)
26H
2O is dissolved in the distilled water that to form calcium concentration be the A solution of 0.1mol/L, places under 0～20 ℃; With Zn (NO
3)
2Be dissolved in the distilled water that to form metal concentration be the B solution of 1.0mol/L, place under 0～20 ℃; (NH
4)
2HPO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 5mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by Zn/ (Zn+Ca) mol ratio of design; An amount of Polyethylene Glycol (PEG) is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of PEG and Ca is PEG: Ca (NO
3)
2=3: 1, Polyethylene Glycol calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of Zn, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 5
With Ca (NO
3)
26H
2O is dissolved in the distilled water that to form calcium concentration be the A solution of 5mol/L, places under 0～20 ℃; With Mn (NO
3)
2Be dissolved in the distilled water that to form metal concentration be the B solution of 1.0mol/L, place under 0～20 ℃; Na
3PO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 5mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by Mn/ (Mn+Ca) mol ratio of design; An amount of Polyethylene Glycol (PEG) is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of PEG and Ca is PEG: Ca (NO
3)
2=3: 1, Polyethylene Glycol calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of Mn, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 6
With Ca (OH)
2Be dissolved in the distilled water that to form calcium concentration be the A solution of 0.1mol/L, place under 0～20 ℃; With La (NO
3)
2Be dissolved in the distilled water that to form metal concentration be the B solution of 0.01mol/L, place under 0～20 ℃; (NH
4)
2HPO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 5mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by La/ (La+Ca) mol ratio of design; An amount of Polyethylene Glycol (PEG) is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the ionic mol ratio of PEG and Ca is PEG: Ca (NO
3)
2=3: 1, Polyethylene Glycol calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain the amorphous nano-calcium phosphate powder of La, and particle diameter is 10nm～50nm, takes out and puts into the exsiccator storage.
Embodiment 7
With Ca (NO
3)
26H
2O is dissolved in the distilled water that to form calcium concentration be the A solution of 2mol/L, places under 0～20 ℃; With Zn (NO
3)
24H
2O and Mg (NO
3)
2With mol ratio is 1/1 to be dissolved in the distilled water that to form metal concentration be the B solution of 1.0mol/L, places under 0～20 ℃; (NH
4)
2HPO
4Be dissolved in the distilled water that to form phosphorus concentration after the stirring and dissolving be the solution of 2mol/L, place under 0～20 ℃; Is 0.1 to be mixed into C solution with A solution and B solution by (Zn+Mg)/(Zn+Mg+Ca) mol ratio of design; An amount of polyacrylic acid is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein polyacrylic acid is 3: 1 in the ionic mol ratio mol ratio of Ca, and polymer calculates with the molal quantity of construction unit.With D solution 5 ℃ of following cold preservations.Treat behind the temperature stabilization under 5 ℃ the speed of phosphorus-containing compound solution with 2ml/min to be added dropwise in the D solution, pH regulates with ammonia and remains on about 10, drips to finish the back reacts 30min under magnetic agitation, and the Ca/P ratio is 1.50.Precipitate is through sucking filtration, washing, and lyophilization must contain Zn, and the amorphous nano-calcium phosphate powder of Mg, particle diameter are 10nm～50nm, takes out and puts into the exsiccator storage.
Claims (6)
1. the preparation method of the non-sizing nano-calcium phosphate powder of medical slow release metal ion is characterized in that may further comprise the steps:
1) calcium containing compound is soluble in water, being mixed with concentration is the A solution of 0.1～5mol/L, places under 0～20 ℃; The metal ion chemical compound is soluble in water, and being mixed with concentration is the B solution of 0.01～1.0mol/L, places under 0～20 ℃; Phosphorus-containing compound is soluble in water, be mixed with the solution that concentration is 0.1～5mol/L, place under 0～20 ℃;
2) a certain proportion of A solution and B solution are mixed formation C solution, wherein the mol ratio of M/ (M+Ca) is 0.0001～0.1, and M represents one or more in Zn, Sr, Mg, La, Eu, Er, Mn, Si, Zr, Na, the K ion;
3) an amount of polymer is dissolved in formation D solution in the C solution, places under 0～20 ℃, wherein the addition of polymer is, the mol ratio of polymer and calcium ion is 1: 10～10: 1, and polymer calculates with the molal quantity of construction unit;
4) be 1.00～2.00 by the Ca/P mol ratio, the phosphorus-containing compound drips of solution is added in the D solution, drip alkaline solution during reaction and regulate pH value 7～12, be reflected at constantly and carry out under the stirring, reaction temperature is 0 ℃～5 ℃, after reaction finished, separation, washing, lyophilization obtained the amorphous nano-calcium phosphate powder of containing metal.
2. press the preparation method of the non-sizing nano-calcium phosphate powder of the described medical slow release metal ion of claim 1, it is characterized in that described calcium containing compound is lime nitrate, calcium chloride or calcium hydroxide.
3. press the preparation method of the non-sizing nano-calcium phosphate powder of the described medical slow release metal ion of claim 1, it is characterized in that described metal ion chemical compound is nitrate or the chloride that contains zinc, strontium, magnesium, lanthanum, europium, erbium, manganese, silicon, zirconium, sodium, potassium ion.
4. press the preparation method of the non-sizing nano-calcium phosphate powder of the described medical slow release metal ion of claim 1, it is characterized in that described phosphorus-containing compound is ammonium hydrogen phosphate, sodium phosphate, phosphoric acid or potassium phosphate.
5. press the preparation method of the non-sizing nano-calcium phosphate powder of the described medical slow release metal ion of claim 1, it is characterized in that described polymer has the functional group that can produce complexing with metal cation, is selected from Polyethylene Glycol or polyacrylic acid.
6. by the preparation method of the non-sizing nano-calcium phosphate powder of the described medical slow release metal ion of claim 1, the alkaline solution that it is characterized in that being used to regulating pH value is ammonia, sodium hydroxide or potassium hydroxide solution.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105498676A (en) * | 2015-11-30 | 2016-04-20 | 中国科学院合肥物质科学研究院 | Sulfur-bearing hydroxyapatite lead ion adsorbent as well as synthetic method and application thereof |
| CN106668934A (en) * | 2016-12-15 | 2017-05-17 | 中山职业技术学院 | Calcium-phosphate-based 3D printing material for biomedicine and preparation method thereof |
| CN109401157A (en) * | 2018-11-30 | 2019-03-01 | 中国科学院金属研究所 | A kind of amorphous calcium phosphate-polyacrylic acid hybrid nano-material and its preparation method and application |
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| US5676976A (en) * | 1995-05-19 | 1997-10-14 | Etex Corporation | Synthesis of reactive amorphous calcium phosphates |
| CN1217855C (en) * | 2003-07-28 | 2005-09-07 | 浙江大学 | Method for preparing biomedical amorphous nano calcium phosphate |
| CN1270783C (en) * | 2003-08-08 | 2006-08-23 | 浙江大学 | Degradable nanometer composite material for biological and medical use |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105498676A (en) * | 2015-11-30 | 2016-04-20 | 中国科学院合肥物质科学研究院 | Sulfur-bearing hydroxyapatite lead ion adsorbent as well as synthetic method and application thereof |
| CN105498676B (en) * | 2015-11-30 | 2018-09-11 | 中国科学院合肥物质科学研究院 | Sulfur-bearing hydroxyapatite adsorbents for lead ion pyrolytic and its synthetic method and application |
| CN106668934A (en) * | 2016-12-15 | 2017-05-17 | 中山职业技术学院 | Calcium-phosphate-based 3D printing material for biomedicine and preparation method thereof |
| CN109401157A (en) * | 2018-11-30 | 2019-03-01 | 中国科学院金属研究所 | A kind of amorphous calcium phosphate-polyacrylic acid hybrid nano-material and its preparation method and application |
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