CN100372577C - Bioactive shell-core multiplelayer microstructure nanometer powder and its preparation method - Google Patents
Bioactive shell-core multiplelayer microstructure nanometer powder and its preparation method Download PDFInfo
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- CN100372577C CN100372577C CNB2006100491795A CN200610049179A CN100372577C CN 100372577 C CN100372577 C CN 100372577C CN B2006100491795 A CNB2006100491795 A CN B2006100491795A CN 200610049179 A CN200610049179 A CN 200610049179A CN 100372577 C CN100372577 C CN 100372577C
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Abstract
The bioactivity shell and core multilayer microstructure nanometer powder disclosed by the present invention is that silica gel is used as an inner core, and porosity calcium phosphate is used as an outer shell. Multilayer microelement zinc or/and spherical particles with strontium ions are distributed between a shell and a core. The aqueous ammonia in an anhydrous alcohol medium is catalyzed into ethyl orthosilicate to form a silica gel nanometer ball through hydrolysis and polycondensation, and a solution containing zinc or the strontium ions is mixed with a suspended aqueous solution of the silica gel nanometer ball. The zinc or the strontium ions are adsorbed at the surface of a silicon nanometer ball and a micropore area, and after silica gel layers are orderly and repeatedly packaged, and the zinc and the strontium ions are adsorbed, the porosity calcium phosphate is redeposited at the surface of the silica gel nanometer ball through filtration and desiccation. A granule regulates the release speed of an inner core active material by changing a microstructure of an outer shell layer, and the explosive release action of active materials of silicon, strontium and zinc does not exist in a short time. The invention has the characteristics that a technology is simple, nanometer size and a layer structure are easily controlled, and the release speed of a bioactive substance is easily regulated and controlled, etc.
Description
Technical field
The present invention relates to a kind of bioactive shell-core multiplelayer microstructure nanometer powder material and preparation method thereof, belong to human tissue injury and repair biomedical materials field.
Background technology
Because of the bones such as bone tooth tissue necrosis due to bone tooth tissue defect, tumor resection and the inflammation due to the wound damaged fast, the holomorphosis reparation is one of clinical medical difficult problem always.Since the beginning of the seventies in last century Hench reported first a kind of CaO, SiO of containing
2, P
2O
5And Na
2The chemical compound of O component fire the bioactivity glass dusty material that forms (trade name: 45S5Bioglass ) can form chemical bonding (synostosis) with human body bone tooth tissue since, the research of bioactive materials has had the history in more than 30 year.Up to now, people also find much with calcium-phosphorus (CaO-P
2O
5) or calcium-silicon (CaO-SiO
2) for the inorganic material on basis can take place directly to combine with osseous tissue, implant and organizational interface zone can not form non-glutinous company property fibrous layer barrier film.Metal and Alloy material more in the past, bioactive materials is greatly improved on bone tooth tissue repair effect and is improved.In the prior art, various calcium-phosphorio bioactive materials is in harmonious proportion the pastel that forms or be applied to clinical with the compound bionic scaffold material of bone matrix collagen with densified sintering product or porous blocks, physiological liquid.Chinese patent CN1446591A discloses a kind of injection-type synthos pastel and has been used for the damaged filling reparation of bone, and in the hope of alleviating patient's misery of performing the operation, but this material biological activity is poor, and needs can degrade fully more than half in vivo in 2 years.Chinese patent CN1416913 is embedded in the complex of bioactie agent BMP, FGF, TGF-β etc. in the synthos pastel, attempt to improve defective tissue Regeneration and Repair speed, multinomial shortcoming makes it be difficult to extensively practice clinically but its cost height, the unstability of bioactie agent and goods should not be sterilized etc.The disclosed a kind of porous calcium phosphate ceramic material of Chinese patent CN1456534 is intended to improve freshman bone tissue's speed and accelerated material degraded of growing into, but calcium-phosphorio material cell in physiological environment is still unresolved to root problems such as material response differences, cambium is grown into the duct based on creeping substitution, and the damaged Regeneration and Repair time of bone is still very long.The disclosed a kind of nano-grade hydroxy apatite of Chinese patent CN1338315/collagen-based composite material has imitated the main inorganic and organic principle in the nature bone substrate on The Nomenclature Composition and Structure of Complexes, for osteoblast adheres to and grow establishment and microenvironment like the body bone tissue inner phase at material surface, but material is in regulating cell perception, feedback and response fast, realize the differentiation of cell fast breeding and bone formation related gene and protein expression aspect deficiency, the main dependent cells of inorganic constituents nano-grade hydroxy apatite approach such as is engulfed and is absorbed.
According to the compatible standard of biomaterial molecule, the ideal material that is used for the damaged Regeneration and Repair of human body bone tooth must possess the active regulation and control that realize osteoblastic proliferation and differentiation simultaneously on cell and molecular level, activating the gene relevant with osteanagenesis expresses fast, " active factors " that host's molecule, cell and tissue accept implant and provide is provided accurately to be regulated and control and replys, reach biological activity (the Chou L that the defective tissue oneself repaired and rebuild the relevant physiological function fast, J.Cell Sci., 1995,108,1563).In the prior art, various CaO, the SiO of containing
2, P
2O
5Calcium-silica-based bioactive materials etc. inorganic constituent element obtains broad research and progressively is applied to clinical.45S5Bioglass is not only inducing osteoid apatite deposition capability, and host bone tissue bond strength and promote to be better than calcium-phosphorio bioactive materials aspect the proliferation and differentiation of osteoblasts, and the silicon of stripping, calcium and phosphonium ion can also activate in the osteoblast a large amount of transcription factor and cell cycle regulatory factors is expressed, and promote the albumen relevant with bone formation such as alkali phosphatase and osteocalcin to express apace.But, be that the bioactivity glass class material fragility of representative is big with 45S5Bioglass , be difficult to be processed into block materials, clinical practice is restricted.It is that main activity inducement material, calcium and P elements are that synergistic activity material, organic polymer are the porous blocks material of carrier with inorganic elements silicon that Chinese patent CN1389184A discloses a kind of, this material can initiatively be induced human body osteoblastic proliferation, differentiation and bone formation related gene and protein expression, and bone formation speeds up.But on preparation method, carry out mechanical combined sorting by material to calcic, silicon, three kinds of compositions of phosphorus, and prepare the inorganic powder particle of different scale by the mechanical ball milling mode, such preparation method is difficult to control material product degradation and biological activity ion dissolution rate, is difficult to obtain osteoblast is produced the active material of the required components compatibility of optimal stimulus.The self assembly of the disclosed a kind of employing surfactant of Chinese patent CN1554607, in conjunction with synthetic mesoporous nano of sol-gel process and mesopore-macropore bio-vitric powder body material.Each constituent element uniform distribution of this material has also restricted active substance and has controllably discharged, and it is too fast that high-ratio surface character has determined active substance to degrade in a short time, will certainly cause cytoactive to descend quick aging and apoptosis.
Along with subject development such as materialogy, chemistry, histology and molecular cytobiologies, bio-medical material of new generation is more and more conceived root problems such as the design of material and behavior from the visual angle of life sciences.It is found that, not only has good cell induction activity by the material of proper proportion processing and preparing by calcium, silicon, three kinds of compositions of phosphorus, and the more necessary trace element of health such as silicon, strontium and zinc etc. are activating osteoblast gene expression, are regulating the osseous tissue calcium concentration, are improving osseous tissue intensity, are promoting also all to have brought into play huge effect (Xynos I.D. in metabolism of bone tissue and the injury repairing, Biochem.Biophys.Res.Commun., 2000,276,461; Marie P.J., Calcif.Tissue Int., 2001,69,121; Ovesen J., Bone, 2001,29,565.); Simultaneously, research finds that also there is remarkable dose-dependence in trace element such as silicon, strontium and zinc to osteoblast activity and the adjusting of osseous tissue growth metabolism, the silicon, strontium or the zinc that discharge too high dose from material can cause cytotoxicity or cause other ion Metabolic disorder (Gough J.E., Biomaterials 2004,25,2039; Dahl S.G., Bone 2001,28, and 446; Ito A., Mater.Sci.Eng.C2002,22,21); Otherwise medium-term and long-term these trace element that lack of osseous tissue will cause tissue distortion even serious disease.In the prior art, many researcheres are attempted to introduce bioactive substances such as silicon, strontium, zinc by approach such as doping in synthos or bioactivity glass, improve the cell induction activity of material, promote cell proliferation and gene expression, accelerate the damaged Regeneration and Repair speed of bone tooth.But traditional sintering process or mechanical mixing all are difficult to trace element is carried out rate of release (Ito A., J.Biomed.Mater.Res., 2000,50,178 of active substance in effectively " management " and any controlled material; Li Y.W., J.Biomed.Mater.Res.2000,52,164), though the sol-gel process technology of preparing of development in recent years can significantly be improved the uniformity of each component, still can't effectively manage and regulate and control arbitrarily the rate of release of trace element to the trace element in the material.
Therefore, according to existing patented technology and pertinent literature report, press for explore a kind of form with behavior on all satisfy the even more ideal active material of the quick and complete reparation of bone tooth tissue defect, such material must possess induce initiatively on cell and molecular level that cell relevant with skeletonization in the human body is bred, differentiation and gene expression, the rate of release of active substance in any controlled material of energy produces the required components compatibility of optimal stimulus to satisfy to the relevant cell of bone formation simultaneously.
Summary of the invention
The purpose of this invention is to provide a kind of bioactive substance rate of release and can freely regulate and control bioactive shell-core multiplelayer microstructure nanometer powder of function admirable and preparation method thereof.
Bioactive shell-core multiplelayer microstructure nanometer powder of the present invention is a kernel with the silicon gel, and the porous synthos are shell, and distribution multilamellar trace element zinc between shell-nuclear is or/and the spheroidal particle of strontium ion, and grain diameter is 30～300 nanometers.
The percetage by weight content that the component of bioactive shell-core multiplelayer microstructure nanometer powder is represented with oxide form is:
CaO 5～40％；
P
2O
5 2～30％；
Above-mentioned porous synthos can be OCP, hypophosphite monohydrate hydrogen calcium or unformed calcium phosphate.
Bioactive shell-core multiplelayer microstructure nanometer powder of the present invention is designated hereinafter simply as Silica@M@OCP, and wherein M represents human body osteogenesis and necessary trace activity substance Zn of metabolism and Sr, and Silica represents the silicon gel, and OCP represents synthos.
The preparation method of bioactive shell-core multiplelayer microstructure nanometer powder of the present invention may further comprise the steps:
1) be 1 in molar ratio with ethyl orthosilicate, ammonia and deionized water: (2～10): (2～10) join in the dehydrated alcohol, the volumetric concentration of control ethyl orthosilicate is 1～10%, this mixed solution is maintained 25～70 ℃, and be continuous stirring more than 2 hours under 200～1200rpm condition at rotating speed, form the silicon gel nano aaerosol solution, filter, use deionized water wash;
2) silicon gel nano is added in the deionized water, and ultra-sonic dispersion, add then and contain zinc ion or strontium ion aqueous solution, the concentration that makes zinc ion or strontium ion is 0.1～100mmol/L, the pH value of regulator solution is 7.6～10.0, continuous stirring under 25～45 ℃ of temperature makes zinc ion or strontium ion be adsorbed in nanosphere surface and micropore inwall thereof;
3) with step 2) nanosphere that is adsorbed with zinc ion or strontium ion that makes is added in the dehydrated alcohol, and ultra-sonic dispersion, add ethyl orthosilicate, ammonia and deionized water then, the mol ratio of ethyl orthosilicate, ammonia and deionized water is 1: (2～10): (2～10), the volumetric concentration of control ethyl orthosilicate is 0.2～4%, with this solution 25～35 ℃ of following continuous stirring more than 2 hours, formation refilters, uses deionized water wash by the composite Nano ball of silicon gel parcel zinc ion or strontium ion;
Repeating step 2 successively) and step 3) 4), obtain zinc ion, refilter, use deionized water wash or/and strontium ion is wrapped in the multi-layer nano ball in the silicon gel;
5) the above-mentioned multi-layer nano ball that makes being scattered in pH value is among silicon saturated aqueous solution 20～200mL of 4.0～8.5, continuous stirring under 35～80 ℃ of temperature, and dripping concentration simultaneously is the Ca that contains of 0.1～20.0mmol/L
2+ Inorganic salt solution 20～200mL, concentration is the PO that contains of 0.05～15mmol/L
4 3- Inorganic salt solution 20～200mL, concentration is the organic polyelectrolyte solution 0.01～10mL that contains carboxyl or amido of 5～25wt%; Dropwise and continue to stir more than 2 hours, refilter, drying.
In the preparation process of the present invention, the said Ca that contains
2+Inorganic salt solution can be Ca (NO
3)
24H
2O or CaCl
2The said PO that contains
4 3-Inorganic salt solution can be Na
3PO
4, Na
2HPO
42H
2O and NaH
2PO
412H
2Among the O any or several.The said zinc ion aqueous solution that contains can be Zn (CH
3COO)
2, Zn (NO
3)
2Perhaps ZnCl
2Containing the strontium ion aqueous solution can be SrCl
2Perhaps Sr (NO
3)
2The said organic polyelectrolyte that contains carboxyl or amido can be polypropylene acid, sodium polyacrylate, poly-Radix Asparagi amino acid or poly-Radix Asparagi amino acid sodium.
Porous synthos shell is OCP, hypophosphite monohydrate hydrogen calcium or unformed calcium phosphate among the present invention, contains Ca by dropping
2+And PO
4 3-The inorganic salt solution process in, the temperature of aaerosol solution and pH value are determined.
In the preparation process of the present invention, contain Ca by change
2+And PO
4 3-Inorganic salt solution dripping quantity, polyelectrolyte dripping quantity and drip after mixing time, the micro structure that can regulate the synthos outer shell.
The present invention does not all exist strict ratio and compatibility restriction to silicon, strontium and the zinc isoreactivity material storage amount of encapsulation.
In the preparation process of the present invention, the disposable adsorption rate of zinc or strontium ion is by the concentration and the pH value decision of zinc in the solution or strontium ion; The encapsulation amount of trace element by Zn or/and the decision of Sr active ion adsorbance and silicon gel parcel number of times.
In the preparation process of the present invention, drip Ca by changing
2+And PO
4 3-The consumption of inorganic salt solution, the ratio that can regulate silicon gel (Silica) and synthos (OCP).
Beneficial effect of the present invention is:
Nano-powder granule of the present invention has shell-core multiplelayer microstructure, kernel is a silicon gel nano, and on different radii, adsorb or/and strontium in conjunction with human body bone health trace elements necessary zinc, outer shell is synthos, the notable attribute of this granule is to regulate the rate of release of kernel active substance by the micro structure that changes outer shell, does not have the behavior that discharges of explosion type in a short time of active substance silicon, strontium, zinc.The present invention prepares all and carries out under 25～80 ℃ of temperature conditions, does not relate to high-temperature heat treatment process, and it is simple to have technology, and a nano-scale and a layer structure are controlled easily, and bioactive substance rate of release speed is easy to characteristics such as regulation and control.
The present invention is not particularly limited the outer shell synthos, packaged material is had no particular limits, except zinc or/and the strontium, as long as can promote metal ions such as active substance that bone tooth tissue injury repairs such as magnesium, ferrum, rare earth, somatomedin and albumen etc. all can be used for the encapsulation in the Silica@M@OCP system, to help detecting, follow the tracks of, location and evaluating material distributes in vivo and the nano-quantum point with fluorescent labeling characteristic of state, magnetic nanoparticle with magnetic imaging all can be used for the encapsulation of Silica@M@OCP system simultaneously.
The goods that utilize biologically active nanometer powder body material of the present invention to make will have excellent safety, biological activity and degradability, be expected to use in orthopaedics, the department of stomatology and minimally-invasive treatment.
Description of drawings
Fig. 1 is an X ray diffracting spectrum, and (a) curve is the collection of illustrative plates of Silica nano-powder among the figure, and (b) curve is Silica@Zn-Sr@OCP
35The collection of illustrative plates of nano-powder, (c) curve is Silica@Zn-Sr@OCP
35The nano-powder ion discharges the collection of illustrative plates of powder body after 60 hours.
Fig. 2 is transmission electron microscope photo and element distribution energy spectrogram, and (a) is that photo, (b) of Silica nano-powder are Silica@Zn-Sr@OCP among the figure
35The photo of nano-powder (c) is Si distribution energy spectrogram, (d) is Sr distribution energy spectrogram, (e) is Zn distribution energy spectrogram.
Fig. 3 is Silica@zn-Sr@OCP
35Nano-powder is at simulated body fluid immersion process intermediate ion concentration curve, wherein figure (a) is the ionic concentration curve of Sr, (b) being the ionic concentration curve of Zn, (c) is the ionic concentration curve of Si, (d) is the ionic concentration curve of Ca ion and P.
The specific embodiment
Further illustrate content of the present invention below in conjunction with example, but these examples do not limit the scope of the invention, all technology that realizes based on foregoing of the present invention and the material of preparation all belong to protection scope of the present invention.Reagent purity that embodiment uses all is not less than its analytical reagent purity index.
(1) gel nano powder preparation:
In the 17.8mL anhydrous ethanol medium, under the magnetic agitation condition, successively add 0.72mL ammonia and 0.58mL deionized water, then the 0.9mL ethyl orthosilicate is joined in the above-mentioned mixed liquor, this silicon sol solution was stirred 6 hours down at 25 ℃.Then, adopt centrifugal filtration process (4000rpm) to carry out solid-liquid separation, with deionized water ultra-sonic dispersion, washing, centrifugalize again, remove the not Ludox of hydrolytic polymerization, drying is 24 hours under 60 ℃ of vacuum, obtains silicon gel nano (as Fig. 1 a collection of illustrative plates and Fig. 2 a photo).
(2) gel nano layer-layer assembling zinc and strontium ion:
The 240mg silicon gel nano is added in the 5.0mL ionized water, ultra-sonic dispersion, adding concentration is the zinc nitrate aqueous solution 200mL of 0.5mmol/L, regulating pH value is 8.0, stirred 8 hours fast, by this high negative electricity character in nanosphere surface, Electrostatic Absorption zinc ion in deionized water solution, centrifugal filtration.Then, this silicon gel nano-powder that is adsorbed with zinc ion is added in the 10mL anhydrous ethanol medium, ultra-sonic dispersion, under the magnetic agitation condition, add 0.3mL ammonia, 0.3mL deionized water and 0.1mL ethyl orthosilicate, this aaerosol solution was stirred 6 hours down at 25 ℃, the silicon gel parcel that particle surface is aggregated, centrifugal filtration.The silicon gel nano that will be enclosed with zinc ion again is added in the 5.0mL ionized water, ultra-sonic dispersion, adding concentration is the strontium nitrate aqueous solution 200mL of 0.5mmol/L, regulating pH value is 9.4, stirred 8 hours fast, by the high negative electricity character of this microsphere surface, Electrostatic Absorption strontium ion in deionized water solution, centrifugal filtration.The nano-powder that again this is adsorbed with strontium ion is added in the 10mL anhydrous ethanol medium, ultra-sonic dispersion, under the magnetic agitation condition, add 0.3mL ammonia, 0.3mL deionized water and 0.1mL ethyl orthosilicate, this aaerosol solution was stirred 6 hours down at 25 ℃, the silicon gel parcel that particle surface is aggregated, centrifugal filtration.Repeat absorption successively and wrap up 2 times, obtain zinc ion and strontium ion and be wrapped in multi-layer nano ball in the silicon gel.
(3) Silica@Zn-Sr@OCP
35Preparation:
The above-mentioned 120mg nanosphere that obtains is scattered in the saturated aqueous solution of 30mL silicon, and the pH value of regulating aaerosol solution is 6.5, continuous stirring under 37 ℃ of temperature, dripping concentration is the calcium nitrate solution 16mL of 20mmol/L, concentration is the disodium phosphate soln 12mL of 20mmol/L, and adding concentration is the sodium polyacrylate 60 μ L of 25wt%.Continue after being added dropwise to complete to stir 3 hours, centrifugalize obtains being wrapped up the silicon gel and being assembled with zinc ion and the biologically active nanometer powder body Silica@Zn-Sr@OCP of strontium ion by OCP again
35(35 represent the mol ratio of Silica and OCP), grain diameter are that 80～120 nanometers are (as (as Fig. 1 b collection of illustrative plates and Fig. 2 b-e photo).
(1) gel nano powder preparation:
With step (1) operation among the embodiment 1.
(2) gel nano layer-layer assembling zinc ion:
120mg Silica nanosphere is added in the 2.5mL ionized water, ultra-sonic dispersion, adding concentration is the zinc nitrate aqueous solution 100mL of 5mmol/L, regulating pH value is 8.2, stirs Silica nanosphere surface adsorption zinc ion, centrifugal filtration fast 6 hours.Then, this nano-powder that is adsorbed with zinc ion is added in the 5mL anhydrous ethanol medium, and ultra-sonic dispersion adds 0.2mL ammonia, 0.2mL deionized water and 0.08mL ethyl orthosilicate under the magnetic agitation condition, this aaerosol solution was stirred 6 hours centrifugal filtration down at 35 ℃.Repeat absorption and wrap up 3 times by above-mentioned steps, obtain zinc ion and be wrapped in multi-layer nano ball in the silicon gel.
(3) Silica@Zn@OCP preparation:
With step (3) operation among the embodiment 1.The nanosphere of 0.12g step (2) preparation is scattered in the saturated aqueous solution of 30mL silicon, and the pH value of regulating aaerosol solution is 5.0, continuous stirring under 50 ℃ of temperature, dripping concentration is the calcium nitrate solution 13mL of 20mmol/L, concentration is the disodium phosphate soln 10mL of 20mmol/L, and adding concentration is the sodium polyacrylate 50 μ L of 20wt%.Continue to stir 6 hours after being added dropwise to complete, centrifugal filtration obtains by hypophosphite monohydrate hydrogen calcium parcel silicon gel and is assembled with the biologically active nanometer powder body Silica@Zn@OCP of zinc ion again
40(40 represent the mol ratio of Silica and OCP).
(1) gel nano powder preparation:
With step (1) operation among the embodiment 1.
(2) gel nano layer-layer assembling strontium ion and Silica@Sr@OCP preparation:
Change zinc nitrate aqueous solution in embodiment 2 steps (2) into the strontium nitrate aqueous solution, and will to regulate pH value be 8.2 to change that to regulate pH value be 9.6 into, other operation is with step (2) and (3) among the embodiment 2, can prepare by hypophosphite monohydrate hydrogen calcium and wrap up silicon gel nano and be assembled with the biologically active nanometer powder body Silica@Sr@OCP of strontium ion
40(40 represent the mol ratio of Silica and OCP).
Embodiment 4Silica@Zn-Sr@OCP
35The nano-powder active substance discharges
With homemade simulation human body physiological liquid (SBF) is solution medium, and the inorganic ions that this solution contains is respectively Na
+142.0mmol/L, K
+5.0mmol/L, Ca
2+2.5mmol/L, Mg
2+1.5mmol/L, Cl
-147.8mmol/L, HCO
3 -4.2mmol/L, HPO
4 2-1.0mmol/L, SO
4 2-0.5mmol/L pH value is 7.25.With 400mg Silica@Zn-Sr@OCP
35Nano-powder is distributed in the 200mL SBF solution, continuous oscillation in the water bath with thermostatic control agitator (120rpm), and bath temperature maintains 37 ℃.Section is drawn 5.0mL aaerosol solution and centrifugalize fast at the fixed time respectively, supernatant is used for the ion concentration test, the residual solid nano-powder is with the fresh dispersion of 5.0mL equivalent and transfer to above-mentioned suspension continuation vibration, ion sustained release curve soaks centrifugal filtration obtains after 60 hours the thing phase composition of residual solid nano-powder such as Fig. 1 c collection of illustrative plates as shown in Figure 3.As seen from Figure 3, zinc, strontium and silicon active ion have the sustained release characteristic.
Claims (8)
1. bioactive shell-core multiplelayer microstructure nanometer powder, it is characterized in that it is a kernel with the silicon gel, the porous synthos are shell, and distribution multilamellar trace element zinc between shell-nuclear is or/and the spheroidal particle of strontium ion, grain diameter is 30～300 nanometers, as follows preparation:
1) be 1 in molar ratio with ethyl orthosilicate, ammonia and deionized water: (2～10): (2～10) join in the dehydrated alcohol, the volumetric concentration of control ethyl orthosilicate is 1～10%, this mixed solution is maintained 25～70 ℃, and be continuous stirring more than 2 hours under 200～1200rpm condition at rotating speed, form the silicon gel nano aaerosol solution, filter, use deionized water wash;
2) silicon gel nano is added in the deionized water, and ultra-sonic dispersion, add then and contain zinc ion or strontium ion aqueous solution, the concentration that makes zinc ion or strontium ion is 0.1～100mmol/L, the pH value of regulator solution is 7.6～10.0, continuous stirring under 25～45 ℃ of temperature makes zinc ion or strontium ion be adsorbed in nanosphere surface and micropore inwall thereof;
3) with step 2) nanosphere that is adsorbed with zinc ion or strontium ion that makes is added in the dehydrated alcohol, and ultra-sonic dispersion, add ethyl orthosilicate, ammonia and deionized water then, the mol ratio of ethyl orthosilicate, ammonia and deionized water is 1: (2～10): (2～10), the volumetric concentration of control ethyl orthosilicate is 0.2～4%, with this solution 25～35 ℃ of following continuous stirring more than 2 hours, formation refilters, uses deionized water wash by the composite Nano ball of silicon gel parcel zinc ion or strontium ion;
Repeating step 2 successively) and step 3) 4), obtain zinc ion, refilter, use deionized water wash or/and strontium ion is wrapped in the multi-layer nano ball in the silicon gel;
5) the above-mentioned multi-layer nano ball that makes being scattered in pH value is among silicon saturated aqueous solution 20～200mL of 4.0～8.5, continuous stirring under 35～80 ℃ of temperature, and dripping concentration simultaneously is the Ca that contains of 0.1～20.0mmol/L
2+Inorganic salt solution 20～200mL, concentration is the PO that contains of 0.05～15mmol/L
4 3-Inorganic salt solution 20～200mL, concentration is the organic polyelectrolyte solution 0.01～10mL that contains carboxyl or amido of 5～25wt%; Dropwise and continue to stir more than 2 hours, refilter, drying.
2. bioactive shell-core multiplelayer microstructure nanometer powder according to claim 1 is characterized in that the percetage by weight content that its component is represented with oxide form is:
SiO
2 40～90％；
CaO 5～40％；
P
2O
5 2～30％；
ZnO 0～30％；
SrO 0～30%, and the said components sum is 100%, and ZnO and SrO are not 0 simultaneously.
3. bioactive shell-core multiplelayer microstructure nanometer powder according to claim 1 is characterized in that said porous synthos are OCP, hypophosphite monohydrate hydrogen calcium or unformed calcium phosphate.
4. the preparation method of bioactive shell-core multiplelayer microstructure nanometer powder according to claim 1 is characterized in that may further comprise the steps:
1) be 1 in molar ratio with ethyl orthosilicate, ammonia and deionized water: (2～10): (2～10) join in the dehydrated alcohol, the volumetric concentration of control ethyl orthosilicate is 1～10%, this mixed solution is maintained 25～70 ℃, and be continuous stirring more than 2 hours under 200～1200rpm condition at rotating speed, form the silicon gel nano aaerosol solution, filter, use deionized water wash;
2) silicon gel nano is added in the deionized water, and ultra-sonic dispersion, add then and contain zinc ion or strontium ion aqueous solution, the concentration that makes zinc ion or strontium ion is 0.1～100mmol/L, the pH value of regulator solution is 7.6～10.0, continuous stirring under 25～45 ℃ of temperature makes zinc ion or strontium ion be adsorbed in nanosphere surface and micropore inwall thereof;
3) with step 2) nanosphere that is adsorbed with zinc ion or strontium ion that makes is added in the dehydrated alcohol, and ultra-sonic dispersion, add ethyl orthosilicate, ammonia and deionized water then, the mol ratio of ethyl orthosilicate, ammonia and deionized water is 1: (2～10): (2～10), the volumetric concentration of control ethyl orthosilicate is 0.2～4%, with this solution 25～35 ℃ of following continuous stirring more than 2 hours, formation refilters, uses deionized water wash by the composite Nano ball of silicon gel parcel zinc ion or strontium ion;
Repeating step 2 successively) and step 3) 4), obtain zinc ion, refilter, use deionized water wash or/and strontium ion is wrapped in the multi-layer nano ball in the silicon gel;
5) the above-mentioned multi-layer nano ball that makes being scattered in pH value is among silicon saturated aqueous solution 20～200mL of 4.0～8.5, continuous stirring under 35～80 ℃ of temperature, and dripping concentration simultaneously is the Ca that contains of 0.1～20.0mmol/L
2+Inorganic salt solution 20～200mL, concentration is the PO that contains of 0.05～15mmol/L
4 3-Inorganic salt solution 20～200mL, concentration is the organic polyelectrolyte solution 0.01～10mL that contains carboxyl or amido of 5～25wt%; Dropwise and continue to stir more than 2 hours, refilter, drying.
5. the preparation method of bioactive shell-core multiplelayer microstructure nanometer powder according to claim 4 is characterized in that the said Ca of containing
2+Inorganic salt solution be Ca (O
3)
24H
2O or CaCl
2
6. the preparation method of bioactive shell-core multiplelayer microstructure nanometer powder according to claim 4 is characterized in that the said PO of containing
4 3-Inorganic salt solution be Na
3PO
4, Na
2HPO
42H
2O and NaH
2PO
412H
2Among the O any or several.
7. the preparation method of bioactive shell-core multiplelayer microstructure nanometer powder according to claim 4 is characterized in that the said zinc ion aqueous solution that contains is Zn (CH
3COO)
2, Zn (NO
3)
2Perhaps ZnCl
2Containing the strontium ion aqueous solution is SrCl
2Perhaps Sr (NO
3)
2
8. the preparation method of bioactive shell-core multiplelayer microstructure nanometer powder according to claim 4 is characterized in that the said organic polyelectrolyte that contains carboxyl or amido is polypropylene acid, sodium polyacrylate, poly-Radix Asparagi amino acid or poly-Radix Asparagi amino acid sodium.
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| CN110538345B (en) * | 2019-10-11 | 2021-09-24 | 上海交通大学医学院附属第九人民医院 | Biological material, preparation method thereof and application thereof in bone repair |
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| CN113769162B (en) * | 2021-09-14 | 2022-09-13 | 武汉大学 | Preparation method of polyvinylpyrrolidone iodine loaded biomimetic mineralized microspheres for treating infectious bone defects |
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| WO2005035016A1 (en) * | 2003-10-16 | 2005-04-21 | Centro Nacional De Investigaciones Científicas (Cinc). | Composite biomaterials for bone implants |
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| CN1562834A (en) * | 2004-03-26 | 2005-01-12 | 中国科学院上海硅酸盐研究所 | Degradable porous glass rack having bioactivity and preparation method |
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| 生物矿化材料的形成机制及模拟应用. 杜竹玮.有色金属，第55卷第4期. 2003 * |
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