CN103466580A - Preparation method of hydroxyapatite microspheres - Google Patents
Preparation method of hydroxyapatite microspheres Download PDFInfo
- Publication number
- CN103466580A CN103466580A CN2013103493523A CN201310349352A CN103466580A CN 103466580 A CN103466580 A CN 103466580A CN 2013103493523 A CN2013103493523 A CN 2013103493523A CN 201310349352 A CN201310349352 A CN 201310349352A CN 103466580 A CN103466580 A CN 103466580A
- Authority
- CN
- China
- Prior art keywords
- hydroxyapatite
- sphere
- calcium carbonate
- preparation
- hydroxyapatite micro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 title abstract 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 91
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 49
- 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 49
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 45
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 23
- 239000010452 phosphate Substances 0.000 claims abstract description 23
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000000243 solution Substances 0.000 claims description 44
- 239000004005 microsphere Substances 0.000 claims description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000007788 liquid Substances 0.000 claims description 24
- 239000000725 suspension Substances 0.000 claims description 24
- 239000008367 deionised water Substances 0.000 claims description 22
- 229910021641 deionized water Inorganic materials 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 238000010438 heat treatment Methods 0.000 claims description 15
- 230000035484 reaction time Effects 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 238000001914 filtration Methods 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 12
- 239000012065 filter cake Substances 0.000 claims description 12
- 230000001105 regulatory effect Effects 0.000 claims description 12
- 238000000967 suction filtration Methods 0.000 claims description 12
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 9
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 9
- 235000019800 disodium phosphate Nutrition 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 7
- 239000012670 alkaline solution Substances 0.000 claims description 4
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 3
- 150000003016 phosphoric acids Chemical class 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 abstract description 34
- 238000006243 chemical reaction Methods 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 7
- 238000001027 hydrothermal synthesis Methods 0.000 abstract description 5
- 238000009818 secondary granulation Methods 0.000 abstract description 3
- 238000005349 anion exchange Methods 0.000 abstract description 2
- 238000009826 distribution Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 238000000465 moulding Methods 0.000 abstract 2
- 238000001308 synthesis method Methods 0.000 abstract 2
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 239000012876 carrier material Substances 0.000 abstract 1
- 230000001788 irregular Effects 0.000 abstract 1
- 239000002243 precursor Substances 0.000 abstract 1
- 230000005855 radiation Effects 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 239000002105 nanoparticle Substances 0.000 description 11
- 239000008187 granular material Substances 0.000 description 10
- 238000002441 X-ray diffraction Methods 0.000 description 8
- 238000010812 external standard method Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 230000009466 transformation Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 3
- 229910010272 inorganic material Inorganic materials 0.000 description 3
- 239000011147 inorganic material Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229910021532 Calcite Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- MWKXCSMICWVRGW-UHFFFAOYSA-N calcium;phosphane Chemical compound P.[Ca] MWKXCSMICWVRGW-UHFFFAOYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- 238000004375 physisorption Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 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 1
Images
Landscapes
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of hydroxyapatite microspheres. Methods for synthesizing spherical hydroxyapatite at present mainly comprise a secondary granulation molding method and a direct synthesis method, and the secondary granulation molding method has a high cost because of high apparatus requirements, strict reaction conditions and large energy consumption. Particles prepared through the direct synthesis method have a wide particle size distribution and have an irregular morphology. The method disclosed in the invention comprises the following steps: placing spherical calcium carbonate in an aqueous solution of phosphate as a precursor template, carrying out a hydrothermal method and a microwave radiation method, and carrying out an anion exchange reaction to prepare the hydroxyapatite microspheres. The method disclosed in the invention has the characteristics of rapid reaction, simple operation process, no need of template removal and the like. The obtained hydroxyapatite microspheres can be widely used in the biomedical field as an ideal carrier material for drug sustained release.
Description
Technical field
The invention belongs to the lithotroph field of medical materials, be specifically related to a kind of preparation method of hydroxyapatite micro-sphere.
Background technology
In organizational engineering, Microspheres Technique is an important technology.Microballoon can be used as the carrier of seed cell and medicine etc., also can be used in the tissue engineering bracket preparation.The microballoon medicine carrying with respect to the support medicine carrying have the controlled release ability strong, can realize the advantages (Cui Daichao, model rural area, 2010) such as multi-medicament sequentially discharges.Aspect cell cultures, it can provide three-dimensional environment, has simulated the phenotype that cell growing environment in vivo is conducive to cell; In addition, traditional nano material is because very easily reunite, and simple, while relying under physisorption medicine carrying, drug loading is limited; And that the micron-size spherical inorganic materials has tap density is large, good fluidity, the characteristics such as workability is good.
Hydroxyapatite is a kind of important inorganic composition part in skeleton and tooth, because it has good biocompatibility, osteoconductive, mobility and adsorptivity, and is widely used in the aspects such as bone tissue engineer technology.The hydroxyapatite material of the variforms such as in recent years,, for meeting different application demands, that investigators have prepared is spherical, bar-shaped, sheet, crystal whisker-shaped.In these forms, spherical hydroxyapatite has the advantages such as good fluidity, specific surface area is high, affinity good, compactedness is high, minimum tumor promotion rate and receives great concern.At present, the main secondary granulation method of forming of the method for synthesizing spherical hydroxyapatite and direct synthesis technique, wherein post forming method comprises plasma fusion, spray-drying process.These class methods are higher to equipment requirements because of it, severe reaction conditions, and energy consumption causes cost high greatly, is unfavorable for practical application in industry production.Direct synthesis technique mainly is divided into two kinds: a kind of is to utilize calcium salt and phosphoric acid salt as raw material, by the parameters such as stoichiometric ratio, pH value, ionic strength, temperature in the furnishing reaction process, directly controls the synthetic particle with certain special appearance, specific dimensions and microstructure.Usually, the prepared particle diameter of this kind of method is distributed more widely, and pattern is rule not.Another kind is to using the large flexible organic molecule of structurally variable as the soft template method of template and using to have the hard template method of the material of rigid structure as template, by ion exchange reaction, synthesizes the particle of preparing desired structure and pattern.Calcium carbonate, as a kind of important inorganic materials, because it has good biocompatibility and pattern highly variable, and becomes the desirable template material for preparing hydroxyapatite, existing Patents file.Prepared the hydroxyapatite active material as Chinese patent (patent No. 97103827.9) utilizes natural coral calcium carbonate under hydrothermal condition, Chinese patent (number of patent application 200310107928.1) discloses a kind of hydrothermal method of utilizing and coral calcium carbonate has been converted into to the preparation method of porous hydroxyapatite.It is worthy of note, the two is simple utilizes hydrothermal method, and the reaction times, reaction process was slow all more than a couple of days, is unfavorable for that industry produces fast.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, a kind of preparation method of hydroxyapatite micro-sphere is provided, has usingd spherical calcium carbonate as pioneer's template, be placed in aqueous phosphatic, be aided with microwave irradiation on the basis of hydrothermal method, by anion exchange reaction, prepare hydroxyapatite micro-sphere.
Concrete grammar of the present invention comprises the following steps:
Step (1). regulate with alkaline solution the aqueous phosphatic that concentration is 2.17～27.6g/L, until the pH value is 10;
Described alkaline solution is sodium hydroxide solution or potassium hydroxide solution, and its concentration is 0.1～1mol/L.
Described phosphoric acid salt is Sodium phosphate dibasic, dipotassium hydrogen phosphate, SODIUM PHOSPHATE, MONOBASIC or potassium primary phosphate.
Step (2). add calcium carbonate powders in the aqueous phosphatic after regulating the pH value, and stir at normal temperatures the formation suspension liquid; The calcium carbonate added and phosphatic mol ratio are 1:0.6～7.5.
The granule-morphology of described calcium carbonate powders is spherical.
Step (3). the suspension liquid of gained is placed in to the microwave oven reacting by heating, and the microwave firepower is 60～100W, and the reaction times is 5～15min.
Described microwave oven is commercially available common microwave stove.
Step (4). by the solution filter after step (3) heating, and replace flush cake respectively more than 3 times with deionized water, dehydrated alcohol.
The millipore filtration suction filtration that described filtration is is 0.1～0.22 μ m by filtrate with aperture.
Step (5). the filter cake of rinsing well in step (4) is put into to thermostatic drying chamber dry, then solid matter is ground to form to dry powder, obtain hydroxyapatite micro-sphere.
Described drying conditions is dry 24～48h under 40～60 ℃.
The present invention can recently prepare the single dispersion hydroxyapatite micro-sphere that size distribution is even, sphericity is high by control reaction times, microwave firepower, calcium phosphorus mole.The ball shaped hydroxy-apatite median size that the present invention prepares is 6.0～7.0 μ m, and particle surface is open microvoid structure by fine hair shape nanoparticle weave in, is a kind of ideal material as pharmaceutical carrier.In addition, by changing reaction parameter, can prepare the residual hydroxyapatite micro-sphere that a certain amount of calcium carbonate is arranged.
The invention has the beneficial effects as follows:
The present invention be take hydrothermal method as basis, is aided with microwave irradiation Reaction time shorten greatly, prepares hydroxyapatite micro-sphere in short several minutes, thereby has improved production efficiency.
The present invention utilizes calcium carbonate structure, pattern, characteristics easy to control in size, by microwave hydrothermal, reacts and is translated into hydroxyapatite, and the particle of gained has retained pattern and the size of calcium carbonate.
Calcium carbonate is the inorganic materials of a class good biocompatibility, utilizes calcium carbonate to prepare hydroxyapatite without removing template as template, thereby has avoided the problems such as pollution of template to final sample.On the contrary, the difference due to calcium carbonate and calcium phosphate degradation rate, can realize the control to the hydroxyapatite degradation rate.
Reaction conditions gentleness of the present invention, operating process is simple, is swift in response.
The accompanying drawing explanation
The field emission scanning electron microscope figure that Fig. 1～4 are hydroxyapatite micro-sphere in the embodiment of the present invention; Wherein (a) is the low power scanning electron microscope (SEM) photograph; (b) be the high power scanning electron microscope (SEM) photograph;
The x-ray diffraction pattern that Fig. 5～7 are hydroxyapatite micro-sphere in the embodiment of the present invention;
Fourier's infrared spectrogram that Fig. 8 is hydroxyapatite micro-sphere in the embodiment of the present invention.
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1
(1) by 0.434g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide that concentration is 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 80W, and the reaction times is 15min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.1 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 40
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 24h.
After testing: the prepared microballoon principal phase of embodiment 1 is hydroxyapatite, particle diameter is about 6.8 μ m, the microsphere surface thin layer is comprised of the rod-like nano particle, and these nanoparticle weave ins present fine and close microvoid structure (as Fig. 1), and residual calcium carbonate diffraction peak more (as Fig. 5).
withanalytical pure calcium carbonate and analytical pure hydroxyapatite are formulated typical curve as standard specimen, utilize the external standard method in the X-ray diffraction quantitative analysis method to analyze phase content in the gained particle.In the known particle of analytical results, the transformation efficiency of calcium carbonate is 12.3 ﹪.
Embodiment 2
(1) by 1.808g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 100W, and the reaction times is 5min, carries out the microwave heating reaction.
(5) by the solution after heating, with aperture, being 0.1 μ m, millipore filtration carries out suction filtration, and deionized water, the dehydrated alcohol filter cake for that obtain alternately rinse respectively 4 times, obtains hydroxyapatite micro-sphere after then putting into the dry 48h of thermostatic drying chamber of 40 ℃.
After testing: the prepared microballoon principal phase of embodiment 2 is hydroxyapatite, and particle diameter is about 6.5 μ m, and the microsphere surface thin layer is comprised of shuttle shape nanoparticle, and these nanoparticle weave ins present fine and close microvoid structure (as Fig. 2).The material phase analysis that these particles are carried out shows: in particle, the residual quantity of calcium carbonate is still higher (as figure
6), utilize as known as calcium carbonate content in the analysis of the X-ray diffraction external standard method in embodiment 1 gained particle: in the particle prepared under this condition, the calcium carbonate transformation efficiency is 50.1 ﹪.
Embodiment 3
(1) by 3.616g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 0.1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 60W, and the reaction times is 15min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.15 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 60
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 24h.
After testing: the prepared microballoon principal phase of embodiment 3 is hydroxyapatite, and particle diameter is about 6.0 μ m, and microsphere surface is comprised of acicular nanoparticles, and these nanoparticle weave ins present comparatively open microvoid structure.Utilize as known as calcium carbonate content in the analysis of the X-ray diffraction external standard method in embodiment 1 gained particle: in the particle prepared under this condition, the calcium carbonate transformation efficiency is 71.7 ﹪.
Embodiment 4
(1) by 5.52g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 80W, and the reaction times is 10min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.2 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 60
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 48h.
After testing: the prepared microballoon principal phase of embodiment 4 is hydroxyapatite (as Fig. 3), and particle diameter is about 6.5 μ m, and microsphere surface presents open microvoid structure (as Fig. 3) by fine hair shape nanoparticle weave in.The material phase analysis that these particles are carried out shows: in particle, the residual quantity of calcium carbonate is higher (as figure
7), utilize as known as calcium carbonate content in the analysis of the X-ray diffraction external standard method in embodiment 1 gained particle: in the particle prepared under this condition, the calcium carbonate transformation efficiency is 94.5 ﹪.
Embodiment 5
(1) by 5.52g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 80W, and the reaction times is 5min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 60
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 48h.
After testing: the prepared microballoon principal phase of embodiment 5 is hydroxyapatite, and particle diameter is about 6.3 μ m, and the microsphere surface thin layer presents fine and close microvoid structure (as Fig. 4) by the acicular nanoparticles weave in.Utilize as known as calcium carbonate content in the analysis of the X-ray diffraction external standard method in embodiment 1 gained particle: in the particle prepared under this condition, the calcium carbonate transformation efficiency is 76 ﹪.
Embodiment 6
(1) by 5.52g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 80W, and the reaction times is 10min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 60
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 48h.
After testing: the prepared microballoon principal phase of embodiment 6 is hydroxyapatite, and particle diameter is about 7 μ m, and the microsphere surface thin layer presents open microvoid structure by fine hair shape nanoparticle weave in.Utilize as the X-ray diffraction external standard method in embodiment 1 and analyze calcium carbonate content in the gained particle, in the particle prepared under known this condition, the calcium carbonate transformation efficiency is 79.8 ﹪.
Embodiment 7
(1) by 5.52g Sodium phosphate dibasic (Na
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 60W, and the reaction times is 15min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse each 3 times, then put into 60
oobtain hydroxyapatite micro-sphere in the thermostatic drying chamber of C after dry 48h.
After testing: the prepared microballoon principal phase of embodiment 7 is hydroxyapatite, and particle diameter is about 6.3 μ m, and microsphere surface presents fine and close microvoid structure by rod-like nano particle weave in.Utilize as the X-ray diffraction external standard method in embodiment 1 and analyze calcium carbonate content in the gained particle, in the particle prepared under known this condition, the calcium carbonate transformation efficiency is 40.4 ﹪.
Embodiment 8
(1) by 5.52g dipotassium hydrogen phosphate (K
2hPO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the potassium hydroxide of 0.1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 60W, and the reaction times is 15min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse 4 times, then put into 60
oin the thermostatic drying chamber of C, dry 48h, obtain hydroxyapatite micro-sphere.
Embodiment 9
(1) by 5.04g SODIUM PHOSPHATE, MONOBASIC (NaH
2pO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the sodium hydroxide of 0.1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 100W, and the reaction times is 5min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse 5 times, then put into 60
oin the thermostatic drying chamber of C, dry 48h, obtain hydroxyapatite micro-sphere.
(1) by 5.04g SODIUM PHOSPHATE, MONOBASIC (KH
2pO
412H
2o) be dissolved in the 200ml deionized water, be made into phosphate solution.
(2) slowly drip while stirring the potassium hydroxide of 1mol/L in above-mentioned solution, until the pH value reaches 10.
(3) add the 0.2g calcium carbonate granule in the phosphate solution of step (2), and constantly stir the formation suspension liquid.
(4) suspension liquid of gained is put into to microwave oven, regulating the microwave firepower is 80W, and the reaction times is 10min, carries out the microwave heating reaction.
(5) millipore filtration that is 0.22 μ m by reacted solution with aperture carries out suction filtration, and deionized water, the dehydrated alcohol for filter cake that obtain alternately rinse 3 times, then put into 60
oin the thermostatic drying chamber of C, dry 48h, obtain hydroxyapatite micro-sphere.
The granule-morphology of the calcium carbonate powders that embodiment 1～10 is used is spherical.
Embodiment is in conjunction with Fig. 3: prepared hydroxyapatite micro-sphere detects through scanning electron microscope, and grain diameter is even, good dispersity, and the sphericity ideal, particle surface forms open microvoid structure by fine hair shape crystal weave in.
Embodiment is in conjunction with Fig. 7: illustrating that prepared particle principal phase is hydroxyapatite, also contain a small amount of calcite, is the complete calcium carbonate of microballoon inside unreacted.
Embodiment is in conjunction with Fig. 8: conclusion is consistent with Fig. 7.
Finally, it should be noted that above lifted be only the specific embodiment of the invention case.
Obviously, the present invention is not limited only to above examples of implementation, and many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention, all should think protection scope of the present invention.
Claims (5)
1. the preparation method of a hydroxyapatite micro-sphere is characterized in that the method comprises the following steps:
Step (1). regulate with alkaline solution the aqueous phosphatic that concentration is 2.17～27.6g/L, until the pH value is 10;
Step (2). add calcium carbonate powders in the aqueous phosphatic after regulating the pH value, and stir at normal temperatures the formation suspension liquid; The calcium carbonate added and phosphatic mol ratio are 1:0.6～7.5;
Step (3). the suspension liquid of gained is placed in to the microwave oven reacting by heating, and the microwave firepower is 60～100W, and the reaction times is 5～15min;
Step (4). by the solution filter after step (3) heating, and replace flush cake respectively more than 3 times with deionized water, dehydrated alcohol;
Step (5). the filter cake of rinsing well in step (4) is put into to thermostatic drying chamber, and under 40～60 ℃, dry 24～48h, then grind to form dry powder by solid matter, obtains hydroxyapatite micro-sphere.
2. the preparation method of a kind of hydroxyapatite micro-sphere as claimed in claim, is characterized in that described alkaline solution is sodium hydroxide solution or potassium hydroxide solution, and its concentration is 0.1～1mol/L.
3. the preparation method of a kind of hydroxyapatite micro-sphere as claimed in claim, is characterized in that the described phosphoric acid salt of step (2) is Sodium phosphate dibasic, dipotassium hydrogen phosphate, SODIUM PHOSPHATE, MONOBASIC or potassium primary phosphate.
4. the preparation method of a kind of hydroxyapatite micro-sphere as claimed in claim, is characterized in that the granule-morphology of the described calcium carbonate powders of step (2) is spherical.
5. the preparation method of a kind of hydroxyapatite micro-sphere as claimed in claim, is characterized in that the described filtration of step (4) is the millipore filtration suction filtration that is 0.1～0.22 μ m by filtrate with aperture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013103493523A CN103466580A (en) | 2013-08-12 | 2013-08-12 | Preparation method of hydroxyapatite microspheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013103493523A CN103466580A (en) | 2013-08-12 | 2013-08-12 | Preparation method of hydroxyapatite microspheres |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103466580A true CN103466580A (en) | 2013-12-25 |
Family
ID=49791671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013103493523A Pending CN103466580A (en) | 2013-08-12 | 2013-08-12 | Preparation method of hydroxyapatite microspheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103466580A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104058380A (en) * | 2014-07-07 | 2014-09-24 | 中国科学院理化技术研究所 | Preparation method of ellipsoidal ion-doped hydroxyapatite microspheres with porous surfaces |
| CN105347322A (en) * | 2015-12-08 | 2016-02-24 | 浙江理工大学 | Spherical nano-porous hydroxylapatite prepared through shells and preparation method thereof |
| CN110182778A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of nano-grade hydroxy apatite raw powder's production technology |
| CN110653248A (en) * | 2019-10-09 | 2020-01-07 | 安徽省农业科学院土壤肥料研究所 | Composite passivation material suitable for arsenic, cadmium and lead polluted rice field and application thereof |
| CN112125290A (en) * | 2020-09-15 | 2020-12-25 | 上海摩漾生物科技有限公司 | Calcium-phosphorus microsphere material containing defect sites and preparation and application thereof |
| CN114574058A (en) * | 2022-02-12 | 2022-06-03 | 固克节能科技股份有限公司 | Single-component water-based flashing building coating and preparation method thereof |
| CN114890398A (en) * | 2017-04-07 | 2022-08-12 | 上海瑞邦生物材料有限公司 | Hydroxyapatite microspheres and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002037613A (en) * | 2000-07-21 | 2002-02-06 | Seki Co Ltd | Method of producing hydroxyapatite |
| KR20050101013A (en) * | 2004-04-16 | 2005-10-20 | 이병택 | Preparation method of high purity nano-sized hydroxyapatite |
| KR100787526B1 (en) * | 2006-12-29 | 2007-12-21 | 순천향대학교 산학협력단 | Preparation of spherical hydroxide apatite, α-ｔｒｉｃａｌｃｉｕｍ ｐｈｏｓｐｈａｔｅ, β-ｔｒｉｃａｌｃｉｕｍ ｐｈｏｓｐｈａｔｅ nanopowder according to microwave and pH control |
| CN102139866A (en) * | 2010-09-28 | 2011-08-03 | 上海师范大学 | Method for preparing magnetic mesoporous apatite microsphere material by utilizing hydrothermal method |
| CN102674285A (en) * | 2012-05-14 | 2012-09-19 | 上海师范大学 | Preparation method of hollow carbonate radical type hydroxyapatite |
| CN102826525A (en) * | 2011-06-13 | 2012-12-19 | 中国科学院上海硅酸盐研究所 | Hard template hydroxyapatite powder morphology hydrothermal controlling method |
| CN102826524A (en) * | 2011-06-13 | 2012-12-19 | 华东理工大学 | Mesoporous hydroxyapatite nonoparticles prepared by microwave-ultrasonic method, and application thereof |
| CN103110952A (en) * | 2013-03-05 | 2013-05-22 | 中国科学院上海硅酸盐研究所 | Microwave-assisted preparation method of hydroxylapatite nanometer structure porous microspheres |
-
2013
- 2013-08-12 CN CN2013103493523A patent/CN103466580A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002037613A (en) * | 2000-07-21 | 2002-02-06 | Seki Co Ltd | Method of producing hydroxyapatite |
| KR20050101013A (en) * | 2004-04-16 | 2005-10-20 | 이병택 | Preparation method of high purity nano-sized hydroxyapatite |
| KR100787526B1 (en) * | 2006-12-29 | 2007-12-21 | 순천향대학교 산학협력단 | Preparation of spherical hydroxide apatite, α-ｔｒｉｃａｌｃｉｕｍ ｐｈｏｓｐｈａｔｅ, β-ｔｒｉｃａｌｃｉｕｍ ｐｈｏｓｐｈａｔｅ nanopowder according to microwave and pH control |
| CN102139866A (en) * | 2010-09-28 | 2011-08-03 | 上海师范大学 | Method for preparing magnetic mesoporous apatite microsphere material by utilizing hydrothermal method |
| CN102826525A (en) * | 2011-06-13 | 2012-12-19 | 中国科学院上海硅酸盐研究所 | Hard template hydroxyapatite powder morphology hydrothermal controlling method |
| CN102826524A (en) * | 2011-06-13 | 2012-12-19 | 华东理工大学 | Mesoporous hydroxyapatite nonoparticles prepared by microwave-ultrasonic method, and application thereof |
| CN102674285A (en) * | 2012-05-14 | 2012-09-19 | 上海师范大学 | Preparation method of hollow carbonate radical type hydroxyapatite |
| CN103110952A (en) * | 2013-03-05 | 2013-05-22 | 中国科学院上海硅酸盐研究所 | Microwave-assisted preparation method of hydroxylapatite nanometer structure porous microspheres |
Non-Patent Citations (3)
| Title |
|---|
| 张文龙等: "微波水热转化制备多孔羟基磷灰石微球", 《化工新型材料》, vol. 33, no. 8, 31 August 2005 (2005-08-31), pages 59 - 60 * |
| 张文龙等: "核-壳型方解石/磷灰石复合微粉的微波辅助合成", 《硅酸盐通报》, no. 4, 31 August 2005 (2005-08-31), pages 94 - 95 * |
| 张文龙等: "碳酸钙磷酸化工艺制备多孔球形羟基磷灰石", 《过程工程学报》, vol. 6, no. 1, 28 February 2006 (2006-02-28) * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104058380A (en) * | 2014-07-07 | 2014-09-24 | 中国科学院理化技术研究所 | Preparation method of ellipsoidal ion-doped hydroxyapatite microspheres with porous surfaces |
| CN104058380B (en) * | 2014-07-07 | 2015-11-04 | 中国科学院理化技术研究所 | Preparation method of ellipsoidal ion-doped hydroxyapatite microspheres with porous surfaces |
| CN105347322A (en) * | 2015-12-08 | 2016-02-24 | 浙江理工大学 | Spherical nano-porous hydroxylapatite prepared through shells and preparation method thereof |
| CN105347322B (en) * | 2015-12-08 | 2017-05-03 | 浙江理工大学 | Spherical nano-porous hydroxylapatite prepared through shells and preparation method thereof |
| CN114890398A (en) * | 2017-04-07 | 2022-08-12 | 上海瑞邦生物材料有限公司 | Hydroxyapatite microspheres and preparation method thereof |
| CN110182778A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of nano-grade hydroxy apatite raw powder's production technology |
| CN110653248A (en) * | 2019-10-09 | 2020-01-07 | 安徽省农业科学院土壤肥料研究所 | Composite passivation material suitable for arsenic, cadmium and lead polluted rice field and application thereof |
| CN112125290A (en) * | 2020-09-15 | 2020-12-25 | 上海摩漾生物科技有限公司 | Calcium-phosphorus microsphere material containing defect sites and preparation and application thereof |
| CN114574058A (en) * | 2022-02-12 | 2022-06-03 | 固克节能科技股份有限公司 | Single-component water-based flashing building coating and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103466580A (en) | Preparation method of hydroxyapatite microspheres | |
| CN101734635B (en) | A kind of preparation method of nanometer hydroxyapatite powder | |
| CN107902636B (en) | Selenium-doped hydroxyapatite and preparation method thereof | |
| CN102139866B (en) | Method for preparing magnetic mesoporous apatite microsphere material by hydrothermal method | |
| CN104288830B (en) | A kind of micro-nano bar-shaped bioactivity glass and preparation method and application | |
| CN103520779B (en) | Porous composite biological material containing multiple active ions and preparation method thereof | |
| CN104961114B (en) | Calcium and magnesium phosphate nano structural material and preparation method thereof | |
| CN106115642B (en) | A kind of large scale hydroxyapatite porous microsphere material and preparation method thereof | |
| CN108030956B (en) | Bioactive glass ceramic scaffold for treating tumorous bone defect and its preparation method and application | |
| CN102249206B (en) | Selenium-doped hydroxyapatite and preparation method thereof | |
| CN101920947A (en) | A kind of preparation method of flaky B-type carbonate radical apatite | |
| CN103058159B (en) | Hollow hierarchical hydroxyapatite microspheres and preparation method and application thereof | |
| CN101716370A (en) | Method for preparing nano doped hydroxylapatite powder | |
| CN102100927B (en) | Porous hydroxy calcium phosphate nanometer particle-modified titanium-based titanate nanowire biologic support material and preparation method thereof | |
| CN106966375B (en) | A kind of hydroxyapatite and preparation method thereof of nano bar-shape structure | |
| CN107281547A (en) | A kind of preparation method of injection bone renovating material | |
| CN104944399A (en) | Preparation method for hydroxyapatite microspheres | |
| CN103463677A (en) | Magnetic hierarchically-porous nanometer sustained-release bone restoration material, and preparation method and application thereof | |
| CN102807202A (en) | Hydroxyapatite hollow microsphere and preparation method thereof | |
| CN102583287A (en) | Hydroxyapatite with flower-shaped level nanostructure and preparation method thereof | |
| CN110745804A (en) | A kind of preparation method of rod-shaped hydroxyapatite with controllable length | |
| CN103935973B (en) | The preparation method of radial multilevel hierarchy nanometer hydroxyapatite under neutrallty condition | |
| CN103818892B (en) | A kind of preparation method of submillimeter phosphogypsum ball | |
| CN114395521A (en) | Hollow magnetic calcium phosphate cell microcarrier and preparation method thereof | |
| CN112755243A (en) | Preparation method of magnesium ion-doped beta-TCP particles for bone regeneration |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20131225 |