CN100372577C - A kind of bioactive shell-core multilayer microstructure nanopowder and its preparation method - Google Patents

Abstract

The biologically active shell-core multilayer microstructure nanopowder disclosed by the present invention uses silica gel as the core, porous calcium phosphate salt as the shell, and distributes multi-layer trace element zinc or/and strontium ions between the shell-core. spherical particles. The preparation method is to catalyze the hydrolysis and polycondensation of tetraethyl orthosilicate with ammonia water in an anhydrous ethanol medium to form silica gel nanospheres, then mix the solution containing zinc or strontium ions with the suspension aqueous solution of silica gel nanospheres, and absorb the zinc or strontium ions On the surface of silicon nanospheres and the microporous area, after repeatedly wrapping the silica gel layer and adsorbing zinc and strontium ions in sequence, then depositing porous calcium phosphate salt on the surface of silica gel nanospheres, filtering and drying. The particles can adjust the release rate of active substances in the inner core by changing the microstructure of the outer shell layer, and there is no short-term explosive release behavior of active substances silicon, strontium, and zinc. The invention has the characteristics of simple process, easy control of nanometer size and layer structure, easy control of release rate of bioactive substances and the like.

Description

A kind of bioactive shell-core multilayer microstructure nanopowder and its preparation method

technical field

The invention relates to a bioactive shell-core multilayer microstructure nanopowder material and a preparation method thereof, belonging to the field of biomedical materials for repairing human tissue damage.

Background technique

The rapid and complete regenerative repair of bone defects such as bone and tooth tissue defects caused by trauma, tumor resection and inflammation-induced bone and tooth tissue necrosis has always been one of the difficult problems in clinical medicine. Since the early 1970s, Hench reported for the first time that a bioactive glass powder material (trade name: 45S5Bioglass ) that contains CaO, SiO ₂ , P ₂ O ₅ and Na ₂ O components fired from a compound can be used with the human body. Since the formation of chemical bonds (osseointegration) between bone and tooth tissues, the research on bioactive materials has a history of more than 30 years. So far, it has been found that many inorganic materials based on calcium-phosphorus (CaO-P ₂ O ₅ ) or calcium-silicon (CaO-SiO ₂ ) can be directly combined with bone tissue. Non-adhesive fibrous septa will not form. Compared with previous metal and alloy materials, bioactive materials have greatly improved and improved the effect of bone and tooth tissue repair. In the prior art, various calcium-phosphorus-based bioactive materials are clinically applied in the form of sintered dense or porous blocks, pastes formed by mixing physiological fluids, or biomimetic bone materials compounded with bone matrix collagen. Chinese patent CN1446591A discloses an injectable calcium phosphate salt paste for bone defect filling and repairing, in order to alleviate the patient's surgical pain, but the material has poor biological activity and needs more than two and a half years to completely degrade in the body. Chinese patent CN1416913 embeds complexes of biologically active factors BMP, FGF, TGF-β, etc. in calcium phosphate salt paste in an attempt to increase the speed of regeneration and repair of defective tissue, but its cost is high, the instability of biologically active factors and Products are not suitable for disinfection and many other shortcomings make it difficult to implement a wide range of clinical applications. A porous calcium phosphate ceramic material disclosed in Chinese patent CN1456534 aims to increase the growth rate of new bone tissue and accelerate material degradation. The groin channel is mainly replaced by crawling, and the regeneration and repair time of bone defect is still very long. A nano-scale hydroxyapatite/collagen composite material disclosed in Chinese patent CN1338315 imitates the main inorganic and organic components in the natural bone matrix in terms of composition and structure, and creates the same human bone for the attachment and growth of osteoblasts on the surface of the material. Similar to the microenvironment in the tissue, but the material is insufficient in regulating cell perception, feedback and rapid response, achieving rapid cell proliferation and differentiation, and bone formation-related gene and protein expression. absorb.

According to the molecular compatibility standards of biomaterials, the ideal material for the regeneration and repair of human bone and tooth defects must have the ability to actively regulate the proliferation and differentiation of osteoblasts at the cellular and molecular levels, and activate the rapid expression of genes related to bone regeneration. , realize the accurate regulation and response of the "active factors" provided by the implant on host molecules, cells and tissues, and achieve the biological activity of self-repair of defective tissue and reconstruction of related physiological functions (Chou L, J. Cell Sci., 1995 , 108, 1563). In the prior art, various calcium-silicon-based bioactive materials containing inorganic components such as CaO, SiO ₂ , P ₂ O ₅ , etc. have been extensively studied and gradually applied in clinic. 45S5Bioglass® is not only superior to calcium-phosphorus-based bioactive materials in terms of inducing bone-like apatite deposition, bonding strength with host bone tissue, and promoting osteoblast proliferation and differentiation, but also dissolved silicon, calcium, and phosphorus ions can also activate A large number of transcription factors and cell cycle regulators are expressed in osteoblasts, and promote the rapid expression of proteins related to bone formation, such as alkaline phosphatase and osteocalcin. However, the bioactive glass materials represented by 45S5Bioglass(R) are brittle and difficult to process into bulk materials, and their clinical application is limited. Chinese patent CN1389184A discloses a porous block material with inorganic element silicon as the main activity-inducing substance, calcium and phosphorus elements as synergistic active substances, and organic polymer as the carrier. This material can actively induce the proliferation and differentiation of human osteoblasts The expression of genes and proteins related to bone formation increases the speed of bone formation. However, in terms of the preparation method, it is difficult to control the degradation of materials and biologically active ions by mechanically combining and screening materials containing calcium, silicon, and phosphorus, and preparing inorganic powder particles of different sizes by mechanical ball milling. Dissolution rate, it is difficult to obtain the active material with the required combination of ingredients for optimal stimulation of osteoblasts. Chinese patent CN1554607 discloses a nano-mesoporous and mesoporous-macroporous biological glass powder material synthesized by self-assembly of surfactants and sol-gel method. The uniform distribution of components of this material also restricts the controllable release of active substances. The high specific surface properties determine that the active substances degrade too quickly in a short period of time, which will inevitably lead to decreased cell activity, rapid aging and apoptosis.

With the development of disciplines such as materials science, chemistry, histology, and molecular cell biology, the new generation of biomedical materials is increasingly conceived from the perspective of life sciences to conceive fundamental issues such as material design and behavior. It has been found that not only the materials prepared by processing the three components of calcium, silicon, and phosphorus in an appropriate ratio have excellent cell-inducing activity, but also some trace elements necessary for human health, such as silicon, strontium, and zinc, can activate osteoblast gene expression. , Regulating bone tissue calcium concentration, improving bone tissue strength, promoting bone tissue metabolism and injury repair have also played a huge role (Xynos I.D., Biochem.Biophys.Res.Commun., 2000, 276, 461; Marie P.J., Calcif. Tissue Int., 2001, 69, 121; Ovesen J., Bone, 2001, 29, 565.); At the same time, the study also found that trace elements such as silicon, strontium and zinc have significant effects on the activity of osteoblasts and the growth and metabolism of bone tissue. Dose-dependent, release of excessively high doses of silicon, strontium or zinc from the material can cause cytotoxicity or cause other ionic metabolic disturbances (Gough J.E., Biomaterials 2004, 25, 2039; Dahl S.G., Bone 2001, 28, 446; Ito A ., Mater.Sci.Eng.C2002, 22, 21); On the contrary, long-term lack of these trace elements in bone tissue will cause tissue distortion and even serious diseases. In the prior art, many researchers try to introduce biologically active substances such as silicon, strontium, and zinc into calcium phosphate salt or bioactive glass by doping or other means to improve the cell-inducing activity of the material, promote cell proliferation and gene expression, and accelerate The speed of regeneration and repair of bone and tooth defects. However, traditional sintering or mechanical mixing methods are difficult to effectively "manage" trace elements and arbitrarily regulate the release rate of active substances in materials (Ito A., J. Biomed. Mater. Res., 2000, 50, 178; Li Y.W., J.Biomed.Mater.Res.2000, 52, 164), although the sol-gel preparation technology developed in recent years can significantly improve the uniformity of each component, it is still unable to carry out trace elements in the material. Effectively manage and arbitrarily regulate the release rate of trace elements.

Therefore, according to the existing patented technology and related literature reports, it is urgent to explore a more ideal active material that can satisfy the rapid and complete repair of bone and tooth tissue defects in terms of composition and behavior. It induces the proliferation, differentiation and gene expression of cells related to osteogenesis in the human body, and at the same time can arbitrarily regulate the release rate of active substances in the material to meet the composition compatibility required for optimal stimulation of cells related to bone formation.

Contents of the invention

The purpose of the present invention is to provide a biologically active shell-core multilayer microstructure nanopowder with freely adjustable release rate and excellent performance and a preparation method thereof.

The bioactive shell-core multilayer microstructure nanopowder of the present invention uses silica gel as the core, porous calcium phosphate as the shell, and distributes spherical particles of multilayer trace element zinc or/and strontium ions between the shell and the core , The particle size is 30-300 nanometers.

The weight percent content of the components of the bioactive shell-core multilayer microstructure nanopowder expressed in the form of oxides is:

SiO ₂ 40-90%;

CaO 5～40%;

P ₂ O ₅ 2～30%;

ZnO 0～30%;

SrO 0～30%, the sum of the above components is 100%, and ZnO and SrO are not 0 at the same time.

The above-mentioned porous calcium phosphate salt may be octacalcium phosphate, hydrated calcium hydrogen phosphate or amorphous calcium phosphate.

The biologically active shell-core multilayer microstructure nanopowder of the present invention is hereinafter referred to as Silica@M@OCP, wherein M represents trace active substances Zn and Sr necessary for human bone growth and metabolism, Silica represents silica gel, and OCP stands for calcium phosphate salt.

The preparation method of the bioactive shell-core multilayer microstructure nanopowder of the present invention comprises the following steps:

1) Add ethyl orthosilicate, ammonia water and deionized water in a molar ratio of 1:(2~10):(2~10) to absolute ethanol, and control the volume concentration of ethyl orthosilicate to 1~ 10%, the mixed solution is maintained at 25-70°C, and continuously stirred at a speed of 200-1200rpm for more than 2 hours to form a suspension solution of silica gel nanospheres, which is filtered and washed with deionized water;

2) Add silica gel nanospheres to deionized water and ultrasonically disperse them, then add an aqueous solution containing zinc ions or strontium ions to make the concentration of zinc ions or strontium ions 0.1-100mmol/L, and adjust the pH value of the solution to 7.6 ～10.0, stirring continuously at 25～45℃, so that zinc ions or strontium ions are adsorbed on the surface of the nanosphere and the inner wall of the micropore;

3) Add the nanospheres with zinc ions or strontium ions adsorbed in step 2) to absolute ethanol, and ultrasonically disperse, then add ethyl orthosilicate, ammonia water and deionized water, ethyl orthosilicate, The molar ratio of ammonia water and deionized water is 1:(2～10):(2～10), the volume concentration of tetraethyl orthosilicate is controlled to be 0.2～4%, and the solution is continuously stirred at 25～35°C for 2 Hours or more, forming composite nanospheres with zinc ions or strontium ions wrapped by silica gel, then filtered and washed with deionized water;

4) Repeat step 2) and step 3) in turn to obtain multilayer nanospheres with zinc ions or/and strontium ions wrapped in silica gel, then filter and wash with deionized water;

5) Disperse the multilayered nanospheres prepared above in 20-200 mL of a silicon-saturated aqueous solution with a pH value of 4.0-8.5, continuously stir at a temperature of 35-80° C., and dropwise add 0.1-20.0 mmol/L 20-200 mL of Ca ²⁺ inorganic salt solution, 20-200 mL of inorganic salt solution containing PO ₄ ^3- at a concentration of 0.05-15 mmol/L, 0.01 organic polyelectrolyte solution containing carboxyl or amine groups at a concentration of 5-25 wt % ~10mL; after the dropwise addition, continue to stir for more than 2 hours, then filter and dry.

In the preparation process of the present invention, the Ca ²⁺ -containing inorganic salt solution may be Ca(NO ₃ ) ₂ ·4H ₂ O or CaCl ₂ . The PO ₄ ^3- containing inorganic salt solution may be any one or more of Na ₃ PO ₄ , Na ₂ HPO ₄ ·2H ₂ O and NaH ₂ PO ₄ ·12H ₂ O. The zinc ion-containing aqueous solution may be Zn(CH ₃ COO) ₂ , Zn(NO ₃ ) ₂ or ZnCl ₂ ; the strontium ion-containing aqueous solution may be SrCl ₂ or Sr(NO ₃ ) ₂ . The organic polyelectrolyte containing carboxyl group or amine group can be polyacrylic acid, sodium polyacrylate, polyaspartic acid or sodium polyaspartate.

In the present invention, the porous calcium phosphate shell is octacalcium phosphate, hydrated calcium hydrogen phosphate or amorphous calcium phosphate. During the process of dropping the inorganic salt solution containing Ca ²⁺ and PO ₄ ^3- , the temperature and pH value of the suspension solution Sure.

In the preparation process of the present invention, the microstructure of the calcium phosphate shell layer can be adjusted by changing the dripping amount of the inorganic salt solution containing Ca ²⁺ and PO ₄ ^3- , the dropping amount of the polyelectrolyte and the stirring time after the dropping .

The present invention has no strict ratio and compatibility restrictions on the storage capacity of the encapsulated active materials such as silicon, strontium and zinc.

In the preparation process of the present invention, the one-time adsorption rate of zinc or strontium ions is determined by the concentration and pH value of zinc or strontium ions in the solution; the encapsulation amount of trace elements is determined by the adsorption amount of Zn or/and Sr active ions and the number of times of silica gel wrapping .

During the preparation process of the present invention, the ratio of silica gel (Silica) to calcium phosphate (OCP) can be adjusted by changing the amount of Ca ²⁺ and PO ₄ ^3- inorganic salt solution added dropwise.

The beneficial effects of the present invention are:

The nanopowder particles of the present invention have a shell-core multilayer microstructure, the inner core is a silica gel nanosphere, and the trace elements zinc or/and strontium necessary for human bone health are adsorbed on different radii, and the outer shell is calcium phosphate Salt, the most notable feature of this particle is that the release rate of the active substance in the core can be adjusted by changing the microstructure of the outer shell layer, and there is no short-term explosive release of the active substance silicon, strontium, and zinc. The preparation of the present invention is carried out at a temperature of 25-80°C, does not involve a high-temperature heat treatment process, has the characteristics of simple process, easy control of nanometer size and layer structure, and easy control of the release rate of biologically active substances.

The present invention has no special restrictions on the calcium phosphate salt of the shell layer, and no special restrictions on the encapsulated substances, except for zinc and/or strontium, as long as active substances that can promote the repair of bone and tooth tissue damage, such as magnesium, iron, rare earth and other metal ions , growth factors and proteins can be used for encapsulation in the Silica@M@OCP system, which is beneficial to the detection, tracking, positioning and evaluation of the distribution and state of materials in the body. Nanoparticles can be used in the encapsulation of Silica@M@OCP system at the same time.

Products made of the bioactive nanometer powder material of the present invention have excellent safety, bioactivity and degradability, and are expected to be applied in orthopedics, stomatology and minimally invasive treatment.

Description of drawings

Figure 1 is an X-ray diffraction pattern, in which (a) curve is the spectrum of Silica nano powder, (b) curve is the spectrum of Silica@Zn-Sr@OCP ₃₅ nano powder, (c) curve is Silica@Zn- The spectrum of Sr@OCP _35nm powder after ion release for 60 hours.

Figure 2 is a transmission electron microscope photo and an energy spectrum of element distribution, in which (a) is a photo of Silica nanopowder, (b) is a photo of Silica@Zn-Sr@OCP ₃₅ nanopowder, and (c) is Si distribution Energy spectrum, (d) is the Sr distribution energy spectrum, (e) is the Zn distribution energy spectrum.

Figure 3 is the ion concentration change curve of Silica@zn-Sr@OCP ₃₅ nanometer powder in the simulated body fluid immersion process, in which (a) is the concentration change curve of Sr ions, (b) is the concentration change curve of Zn ions, ( c) is the concentration change curve of Si ions, (d) is the concentration change curves of Ca ions and P ions.

Detailed ways

The content of the present invention is further illustrated below in conjunction with examples, but these examples do not limit the scope of the present invention, and all technologies and materials prepared based on the above contents of the present invention all belong to the protection scope of the present invention. The purity of the reagents used in the examples is not lower than its analytical reagent purity index.

Example 1 Preparation of Silica@Zn-Sr@OCP ₃₅ nanometer powder

(1) Preparation of gel nanosphere powder:

In 17.8mL absolute ethanol medium, add 0.72mL ammonia water and 0.58mL deionized water successively under the condition of magnetic stirring, then add 0.9mL tetraethyl orthosilicate to the above mixed solution, and put the silica sol solution at 25°C Stirring was continued for 6 hours. Then, adopt centrifugal filtration method (4000rpm) to carry out solid-liquid separation, ultrasonically disperse and wash with deionized water, and centrifuge again to remove unhydrolyzed and polymerized silica sol, and dry under vacuum at 60°C for 24 hours to obtain silica gel nanospheres ( Figure 1a map and Figure 2a photo).

(2) Gel nanosphere layer-layer assembly of zinc and strontium ions:

Add 240mg of silica gel nanospheres to 5.0mL of ionized water, ultrasonically disperse, add 200mL of zinc nitrate aqueous solution with a concentration of 0.5mmol/L, adjust the pH value to 8.0, and stir rapidly for 8 hours. , Electrostatically adsorb zinc ions in deionized aqueous solution, and centrifugally filter. Then, add the silica gel nanopowder with zinc ions to 10 mL of absolute ethanol medium, ultrasonically disperse, add 0.3 mL of ammonia water, 0.3 mL of deionized water and 0.1 mL of tetraethyl orthosilicate under magnetic stirring conditions , the suspension solution was stirred at 25°C for 6 hours, the surface of the particles was coated with polymerized silica gel, and centrifugally filtered. Then add the silica gel nanospheres wrapped with zinc ions into 5.0mL of ionized water, ultrasonically disperse, add 200mL of strontium nitrate aqueous solution with a concentration of 0.5mmol/L, adjust the pH value to 9.4, and stir rapidly for 8 hours. High negative charge on the surface, electrostatic adsorption of strontium ions in deionized aqueous solution, centrifugal filtration. Then add the nano-powder with strontium ions to 10mL of absolute ethanol medium, ultrasonically disperse, add 0.3mL of ammonia water, 0.3mL of deionized water and 0.1mL of ethyl orthosilicate under the condition of magnetic stirring, and suspend the The solution was stirred at 25°C for 6 hours, the surface of the particles was coated with polymerized silica gel, and centrifugally filtered. The adsorption and encapsulation are repeated twice in sequence to obtain multilayer nanospheres in which zinc ions and strontium ions are encased in silica gel.

(3) Preparation of Silica@Zn-Sr@OCP ₃₅ :

Disperse 120 mg of nanospheres obtained above in 30 mL of silicon-saturated aqueous solution, adjust the pH of the suspension to 6.5, stir continuously at 37 ° C, and add 16 mL of calcium nitrate solution with a concentration of 20 mmol/L dropwise at a concentration of 20 mmol /L disodium hydrogen phosphate solution 12mL, and add 60μL of sodium polyacrylate with a concentration of 25wt%. Continue to stir for 3 hours after the dropwise addition, and centrifuge to obtain the bioactive nanopowder Silica@Zn-Sr@OCP ₃₅ (35 represents Silica and The molar ratio of OCP), the particle size is 80-120 nanometers (such as (as shown in Fig. 1b map and Fig. 2b-e photos).

Example 2 Preparation of Silica@Zn@OCP ₄₀ nanometer powder

(1) Preparation of gel nanosphere powder:

Operate with step (1) in Example 1.

(2) Gel nanosphere layer-layer assembly of zinc ions:

Add 120mg of Silica nanospheres to 2.5mL of ionized water, ultrasonically disperse, add 100mL of zinc nitrate aqueous solution with a concentration of 5mmol/L, adjust the pH value to 8.2, and stir rapidly for 6 hours. Zinc ions are adsorbed on the surface of Silica nanospheres, and centrifugally filtered. Then, add the nano-powder with zinc ions adsorbed to 5mL of absolute ethanol medium, ultrasonically disperse, add 0.2mL of ammonia water, 0.2mL of deionized water and 0.08mL of ethyl orthosilicate under the condition of magnetic stirring, and the The suspension was stirred at 35°C for 6 hours, and filtered by centrifugation. Repeat the above steps for adsorption and wrapping three times to obtain multilayer nanospheres with zinc ions wrapped in silica gel.

(3) Preparation of Silica@Zn@OCP:

Operate with step (3) in Example 1. Disperse 0.12g of nanospheres prepared in step (2) in 30mL of silicon-saturated aqueous solution, adjust the pH of the suspension to 5.0, stir continuously at 50°C, and add 13mL of calcium nitrate solution with a concentration of 20mmol/L dropwise , 10 mL of disodium hydrogen phosphate solution with a concentration of 20 mmol/L, and 50 μL of sodium polyacrylate with a concentration of 20 wt % was added. Continue to stir for 6 hours after the dropwise addition is completed, and centrifuge to obtain the bioactive nano-powder Silica@Zn@OCP ₄₀ (40 represents the molar ratio of Silica to OCP) coated with silicon gel by hydrated calcium hydrogen phosphate and assembled with zinc ions ).

Example 3 Preparation of Silica@Sr@OCP ₄₀ nanometer powder

(1) Preparation of gel nanosphere powder:

Operate with step (1) in Example 1.

(2) Preparation of gel nanosphere layer-layer assembly of strontium ions and Silica@Sr@OCP:

Zinc nitrate aqueous solution is changed into strontium nitrate aqueous solution in the embodiment 2 step (2), and the adjustment pH value is 8.2 and the adjustment pH value is changed into 9.6, and other operations are with step (2) and (3) in the embodiment 2, can A bioactive nanopowder Silica@Sr@OCP ₄₀ (40 represents the molar ratio of Silica to OCP) was prepared, which was coated with hydrated calcium hydrogen phosphate silica gel nanospheres and assembled with strontium ions.

Embodiment 4 Silica@Zn-Sr@OCP ₃₅ Nano Powder Active Substance Release

The self-made simulated human physiological fluid (SBF) is used as the solution medium, and the inorganic ions contained in the solution are Na ⁺ 142.0mmol/L, K ⁺ 5.0mmol/L, Ca ²⁺ 2.5mmol/L, Mg ²⁺ 1.5mmol/L L, Cl ^- 147.8mmol/L, HCO ₃ ^- 4.2mmol/L, HPO ₄ ^2- 1.0mmol/L, SO ₄ ^2- 0.5mmol/L, pH 7.25. Disperse 400mg of Silica@Zn-Sr@OCP ₃₅ nanometer powder into 200mL of SBF solution, shake continuously (120rpm) in a constant temperature water bath shaker, and maintain the temperature of the water bath at 37°C. Draw 5.0mL of the suspension solution in a predetermined period of time and quickly centrifuge it. The supernatant is used for the ion concentration test. The residual solid nanopowder is freshly dispersed with 5.0mL of the same amount and transferred to the above suspension to continue shaking. The ion-controlled release curve is as follows: As shown in Figure 3, the phase composition of the residual solid nanopowder obtained by centrifugal filtration after soaking for 60 hours is shown in Figure 1c. It can be seen from Figure 3 that the active ions of zinc, strontium and silicon have controlled release characteristics.

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.

Images