CN101822961B - In situ preparation method of hydroxyapatite /chitosan core-shell nanospheres - Google Patents
In situ preparation method of hydroxyapatite /chitosan core-shell nanospheres Download PDFInfo
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Abstract
The invention relates to an in situ preparation method of hydroxyapatite/chitosan core-shell nanospheres, which comprises the steps of: selecting a solvent which is immiscible in water and has low boiling point and higher vapour pressure than water; dispersing aqueous solution containing phosphate groups or pyrophosphate ions in the solvent to form emulsion; preparing aqueous solution containing CS and calcium ions to be used as encapsulation solution; adding the encapsulation solution in the emulsion to form oil-in-water-in-water composite emulsion; and confining the nucleation and growth processes of the hydroxyapatite inside the inner-water phase or at the interface of the inner-water phase and the oil phase by controlling the reaction condition. In this way, solid or hollow HAp nanospheres can be formed, and while the CS molecules diffuse from the inner water phase to the outer water phase, under the effect of the hydrogen bonds of the -OH on the surface of the hydroxyapatite, CS covering layers can be formed on the surfaces of the hydroxyapatite nanospheres at the same time. In this way, hydroxyapatite/chitosan core-shell nanosphere product can be prepared. The grain size of the nanosphere rangs from 100 to 200 nanometers, and the nanosphere is rounded up.
Description
Technical field
The present invention relates to a kind of method of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres.
Background technology
Calcium hydroxy phosphate is the main inorganic composition of vertebrate bone tissue, and artificial-synthetic hydroxyapatite's (HAp) physicochemical property, structure are basic identical with it, have no side effect; Nonirritant; Zoopery and clinical observation prove that all this material is the fabulous bone substitute of a kind of biocompatibility, have the bone guided effect, and inserting after the bone defect and to keep for the deposition of bone matrix provides a good bone bed; The hyperblastosis of guiding surrounding bone; Accelerate osteogenetic process,, thereby promote damaged symphysis for good condition has been created in the reconstruction of new bone.But its fragility and non-workability have limited its application.
Shitosan (CS), i.e. carboxymethyl chitosan, convenient sources is prone to extract, and is the rare positively charged high molecular polymer of nature.Avirulence, nonirritant, sensitization does not react with body fluid and can be had excellent biological compatibility and unique biological activity by the lyase biodegradation of body, and functions such as promotion wound healing, bone formation are arranged, and utilization can be absorbed by the body.Shitosan has certain viscosity, can improve the flowability and the formulation of mixture, anti-inflammatory analgetic is arranged and promote the wound healing effect, is widely used in the preparation of bone tissue engineering scaffold at present.But its mechanical strength is lower, can not satisfy the fixing and treatment to the higher bone injury position of mechanical property requirements.
For giving full play to the pliability of hydroxyapatite superior bioactive and shitosan, the two is carried out compound, can obtain existing good biology performance in theory, there is the bone of excellent mechanical performances to repair substitution material again.Therefore, hydroxyapatite and the compound report as tissue engineering material of shitosan are a lot of at present, but are mostly powder body material or bulk material, and composite methods is mainly in direct blend, co-precipitation, freeze drying and the solidification liquid solidifies.
Research shows that the form of particle and structure are the principal elements that influences particle activity in human body.Medicine carrying particle implant into body in irregular shape can produce inflammatory reaction, so the spherical medicine carrying particle of the regular shape first-selection that is the implant carrier.
Summary of the invention
The object of the present invention is to provide a kind of method of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres, the hydroxyapatite/chitosan core-shell nanospheres that this method obtains has spherical whole characteristics.
For realizing above-mentioned purpose, the present invention realizes through following technical scheme: a kind of method of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres is characterized in that it comprises the steps:
1) in the salt water-soluble (deionized water) with the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion, being made into phosphate anion or phosphoric acid hydrogen radical ion concentration is the solution of 0.3～0.5mol/L; Adding highly basic adjusting pH value then is 11.0～13.0, obtains the aqueous solution (as interior water) of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion;
Press cyclohexane (oil phase): volume ratio=100～2 of the aqueous solution of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion (interior water): 1; Choose cyclohexane (for oil phase); By surfactant is 0.3%～0.5% of cyclohexane (for oil phase) quality, chooses surfactant; Surfactant is dissolved in the cyclohexane, obtains containing the cyclohexane of surfactant;
The aqueous solution of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion is poured in the cyclohexane that contains surfactant, stirred, and sonicated 5～10min, emulsion (w/o type emulsion) obtained;
2) by calcium ion in the calcium salt: mol ratio=1.5～1.67 of phosphate anion or phosphoric acid hydrogen radical ion (being in the salt of salt or phosphoric acid hydrogen radical ion of phosphorus-containing acid ion): 1, choose calcium salt; In calcium salt water-soluble (deionized water), obtain the aqueous solution of the calcium salt of Ca ion concentration≤0.5mol/L;
Mol ratio by calcium ion in the calcium salt and shitosan is 0.001～5000, chooses shitosan; By shitosan: mass concentration is aqueous acetic acid=0.5～2.0g of 1～2.5wt%: 100mL, chooses aqueous acetic acid; Shitosan is dissolved in the aqueous acetic acid, obtains the aqueous acetic acid of chitosan-containing;
The aqueous acetic acid of chitosan-containing is splashed in the aqueous solution of calcium salt, obtain transparent mixed solution (for outer water);
3) press surfactant: mass ratio=0.3～0.5 of mixed solution (outer water): 100, choose surfactant, subsequent use;
With step 2) mixed solution that obtains pours in the emulsion that step 1) obtains, and stirs 5～10min, adds the subsequent use surfactant of step 3), obtains emulsion (W/O/W type emulsion); Emulsion is in 30 ℃～50 ℃ stirring in water bath reaction 44～56h;
4) treat that step 3) reaction finishes after, the solution of layering is got the upper strata emulsion layer, behind 40～50 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol obtains solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres (product) in 40～50 ℃ of vacuum drying.
The salt of said phosphorus-containing acid ion is ammonium dihydrogen phosphate (ADP), sodium phosphate or sodium dihydrogen phosphate.
The salt of said phosphoric acid hydrogen radical ion is diammonium hydrogen phosphate, dibastic sodium phosphate, diammonium hydrogen phosphate, dipotassium hydrogen phosphate or sodium hydrogen phosphate.
The said highly basic of step 1) is NaOH or potassium hydroxide.
The said surfactant of step 1) is sorbester p37 (Span85) or sorbester p17.
Said calcium salt is calcium chloride or calcium nitrate (four water-calcium nitrate).
The molecular weight ranges of said shitosan is 300,000～1,000,000.
The said surfactant of step 3) is Tween 80 (Tween80) or polysorbas20.
The power of said sonicated is 20～200W.
Principle of the present invention: multi-emulsion method is on the basis of traditional emulsion-solvent evaporation method, to improve to form.The principle that this method prepares HAp/CS nucleocapsid ball be select one with the not miscible solvent that boiling point is low, vapour pressure is higher than water of water; The aqueous solution with phosphorous acid group or phosphoric acid hydrogen radical ion is dispersed in the above-mentioned solution then, forms w/o type emulsion.Prepare an aqueous solution that contains CS, calcium ion in addition as parcel solution; Under condition of stirring; This solution is added in the above-mentioned emulsion; Form W/O/W (W/O/W type) emulsion, through control certain reaction condition, make the process of hydroxyapatite nucleation, growth be confined in the interface of water inner or interior water and oil phase; Thereby can form solid or hollow HAp nanosphere; And along with the CS molecule is diffused into interior water from outer water, receive the influence of the hydrogen bond action power of hydroxyapatite surface-OH, form the CS clad synchronously on the surface of hydroxyapatite nano ball.
Hydroxyapatite synthetic reaction equation is as follows:
10Ca
2++6(HPO
4)
2-+2OH
-→Ca
10(PO
4)
6(OH)
2+6H
+(1)
The formation mechanism of hydroxyapatite/chitosan core-shell nanospheres is as shown in Figure 1, when reaction temperature is 50 ℃, and Ca
2+The diffusion velocity that diffuses into interior water from outer water compares Ca
2+With (HPO
4)
2-It is fast that the speed of reaction is wanted, and reaction mainly occurs in interior aqueous phase, generates product HAp; CS is a high molecular polymer; Diffusion velocity is the slowest, when the CS molecule slowly is diffused into hydroxyapatite nano bead when surface, because the HAp surface-there is hydrogen bond action power between the amino of OH and CS molecular surface; CS forms clad on hydroxyapatite nano ball surface, and obtaining product inner is the HAp/CS core-shell nano ball that a plurality of HAp monocrystalline bondings form.
When reaction temperature is 30 ℃, Ca
2+The diffusion velocity that diffuses into interior water from outer water compares Ca
2+With (HPO
4)
2-It is slow that the speed of reaction is wanted, and works as Ca
2+Just react when water is surperficial in diffusing to, water surface in HAp reaction of formation just occurs in, also at product surface formation clad, obtain like this is hollow HAp/CS core-shell nano ball to same CS.
The invention has the beneficial effects as follows: the disordered structure that the present invention is directed to present HAp/CS composite; Adopt the nanosphere of the synthetic a kind of orderly HAp/CS nucleocapsid structure of multi-emulsion method original position; Particle diameter is distributed as between the 100-200nm, and is spherical whole, the particle diameter distribution uniform; Kernel is hollow or solid hydroxyapatite nano ball, and housing is a shitosan, can be that functional modification is carried out in substrate with the chitosan film, to reach the needs of biologically using.Can also drug loading in this core-shell nano ball and other active materials, medicine can be before hydroxyapatite be synthetic, among or add afterwards.
Description of drawings
Fig. 1 is the mechanism sketch map that the hydroxyapatite/chitosan core-shell nanospheres of the embodiment of the invention 1 and embodiment 2 forms.
Fig. 2 a is the solid HAp/CS core-shell nano ball SEM figure of the preparation of the embodiment of the invention 1;
Fig. 2 b is the TEM figure of HAp nanosphere;
Fig. 2 c is the TEM figure of HAp nanosphere;
Fig. 2 d is HAp/CS core-shell nano ball TEM figure;
Fig. 2 e is HAp/CS core-shell nano ball TEM figure.
Fig. 3 is the SEM figure of hollow HAp/CS core-shell nano ball of the preparation of the embodiment of the invention 2.
The specific embodiment
In order to understand the present invention better, further illustrate content of the present invention below in conjunction with embodiment, but content of the present invention not only is confined to following embodiment.
Embodiment 1:
The method of a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres (solid HAp/CS core-shell nano ball), it comprises the steps:
1). take by weighing the 0.8g diammonium hydrogen phosphate and be dissolved in (at this moment, phosphoric acid hydrogen radical ion concentration is 0.3mol/L) in the 21mL deionized water, and use concentrated sodium hydroxide to be dissolved in to regulate the pH value be 12.0, obtain ammonium dihydrogen phosphate; The Span85 that gets 1.5mL is dissolved in the 50mL cyclohexane (Span85 be cyclohexane quality 0.5%), obtains containing the cyclohexane of Span85; Ammonium dihydrogen phosphate is poured in the cyclohexane that contains Span85, and 1500r/mim speed stirs ultrasonic auxiliary emulsification 10min simultaneously, obtains emulsion 1.
2). take by weighing the 19g four water-calcium nitrate and be dissolved in that (the Ca ion concentration is 0.5mol/L in the 160mL deionized water; At this moment; Calcium ion in the four water-calcium nitrate: the mol ratio of phosphoric acid hydrogen radical ion in the diammonium hydrogen phosphate=1.67: 1), be stirred to dissolving fully, obtain calcium nitrate aqueous solution; Preparation 15mL concentration be 1wt% shitosan the 2wt% acetum (at this moment; Mol ratio by calcium ion in the four water-calcium nitrate and shitosan is 100: 1; Shitosan: mass concentration is aqueous acetic acid=1g of 2wt%: 100m L), obtain the aqueous acetic acid of chitosan-containing; The aqueous acetic acid of chitosan-containing is splashed in the calcium nitrate aqueous solution, obtain transparent mixed solution 2.
3). mixed solution 2 is poured in the emulsion 1, after 300r/min speed stirs 10min, add 0.8mL Tween80 (at this moment, Tween80 be mixed solution 2 quality 0.5%), 300r/min stirs 30min and obtains emulsion; Keep the 300r/min mixing speed also with 50 ℃ of water-bath 48h.
4). after treating that step 3) reaction finishes, the solution of layering is got the upper strata emulsion layer, behind 40 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol, obtain solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres (solid HAp/CS core-shell nano ball) in 40 ℃ of vacuum drying.
Fig. 2 a is solid HAp/CS core-shell nano ball SEM; Fig. 2 b, Fig. 2 c are the TEM figure of HAp nanosphere; Fig. 2 d, Fig. 2 e are HAp/CS core-shell nano ball TEM figure.
The HAp/CS core-shell nano spherolite of visible preparation directly is distributed between the 100-200nm from Fig. 2 a, and is spherical whole, the particle diameter distribution uniform, and, be visible as the acicular crystal of HAp without the HAp nanosphere rough surface (Fig. 2 b, Fig. 2 c) that CS coats; And the nucleocapsid ball smooth surface after CS coats, the CS coating thickness is about (Fig. 2 d, Fig. 2 e) about 10nm.
Embodiment 2:
The method of a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres (hollow HAp/CS core-shell nano ball), it comprises the steps:
1). take by weighing the 0.8g diammonium hydrogen phosphate and be dissolved in (phosphoric acid hydrogen radical ion concentration is 0.3mol/L) in the 21mL deionized water, and use concentrated sodium hydroxide to be dissolved in to regulate the pH value be 12.0, obtain ammonium dibasic phosphate solution; The Span85 that gets 1.5mL is dissolved in the 50mL cyclohexane (Span85 be cyclohexane quality 0.5%), obtains containing the cyclohexane of Span85; Ammonium dibasic phosphate solution is poured in the cyclohexane that contains Span85, and 1500r/mim speed stirs ultrasonic auxiliary emulsification 10min simultaneously, obtains emulsion 1.
2). take by weighing the 19g four water-calcium nitrate and be dissolved in that (the Ca ion concentration is 0.5mol/L in the 160mL deionized water; At this moment; Calcium ion in the four water-calcium nitrate: the mol ratio of phosphoric acid hydrogen radical ion in the diammonium hydrogen phosphate=1.67: 1), be stirred to dissolving fully, obtain calcium nitrate aqueous solution; Preparation 15mL concentration be 1wt% shitosan the 2wt% acetum (at this moment; Mol ratio by calcium ion in the four water-calcium nitrate and shitosan is 100: 1; Shitosan: mass concentration is aqueous acetic acid=1g of 2wt%: 100m L), obtain the aqueous acetic acid of chitosan-containing; The aqueous acetic acid of chitosan-containing is splashed in the calcium nitrate aqueous solution, obtain transparent mixed solution 2.
3). mixed solution 2 is poured in the emulsion 1, after 300r/min speed stirs 10min, add 0.8mL Tween80 (at this moment, Tween80 be mixed solution 2 quality 0.5%), 300r/min stirs 30min and obtains emulsion; Keep the 300r/min mixing speed also with 30 ℃ of water-bath 48h.
4). after treating that step 3) reaction finishes, the solution of layering is got the upper strata emulsion layer, behind 40 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol, obtain solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres (product) in 40 ℃ of vacuum drying.
The nucleocapsid ball (product) of preparation is pulverized after SEM observes, from Fig. 3 it is thus clear that under 30 ℃ of conditions, can obtain hollow HAp/CS core-shell nano ball, particle diameter is distributed as between the 100-200nm, and is spherical whole, the particle diameter distribution uniform.
Embodiment 3:
A kind of method of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres, it comprises the steps:
1) sodium phosphate is dissolved in the deionized water, is made into the solution that phosphorus acid ion concentration is 0.3mol/L; Adding NaOH adjusting pH value then is 11.0, obtains the aqueous solution (as interior water) of sodium phosphate;
Press cyclohexane (oil phase): the volume ratio of the aqueous solution of sodium phosphate (interior water)=100: 1, choose cyclohexane (for oil phase), press sorbester p37 (Span85) for 0.3% of cyclohexane (for oil phase) quality, choose sorbester p37 (Span85); (Span85) is dissolved in the cyclohexane with sorbester p37, obtains containing the cyclohexane of sorbester p37 (Span85);
The aqueous solution (interior water) of sodium phosphate is poured in the cyclohexane that contains sorbester p37 (Span85), stirred, and sonicated 5min, emulsion (w/o type emulsion) obtained;
2) press calcium ion in the calcium chloride: the mol ratio of phosphate anion in the sodium phosphate=1.5: 1, choose calcium chloride; In calcium chloride water-soluble (deionized water), obtain the calcium chloride water that the Ca ion concentration is 0.1mol/L; Mol ratio by calcium ion in the calcium chloride and shitosan is 0.001, chooses shitosan; By shitosan: mass concentration is aqueous acetic acid=0.5g of 1wt%: 100mL, chooses aqueous acetic acid; Shitosan is dissolved in the aqueous acetic acid, obtains the aqueous acetic acid of chitosan-containing; The molecular weight ranges of said shitosan is 300,000～1,000,000;
The aqueous acetic acid of chitosan-containing is splashed in the calcium chloride water, obtain transparent mixed solution (for outer water);
3) press Tween 80 (Tween80): the mass ratio of mixed solution (outer water)=0.3: 100, choose Tween 80 (Tween80), subsequent use; With step 2) mixed solution that obtains pours in the emulsion that step 1) obtains, and stirs 5min, adds Tween 80, obtains emulsion (W/O/W type emulsion); Emulsion is in 30 ℃ of stirring in water bath reaction 44h;
4) treat that step 3) reaction finishes after, the solution of layering is got the upper strata emulsion layer, behind 40 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol obtains solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres (product) in 40 ℃ of vacuum drying.
The hydroxyapatite/chitosan core-shell nanospheres (product) of preparation is pulverized after SEM observes, and particle diameter is distributed as between the 100-200nm, and is spherical whole, the particle diameter distribution uniform.
Embodiment 4:
A kind of method of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres, it comprises the steps:
1) with in the dipotassium hydrogen phosphate water-soluble (deionized water), is made into the solution that phosphoric acid hydrogen radical ion concentration is 0.5mol/L; Adding potassium hydroxide adjusting pH value then is 13.0, obtains aqueous dibasic potassium phosphate solution (as interior water);
Press cyclohexane (oil phase): the volume ratio of aqueous dibasic potassium phosphate solution (interior water)=2: 1, choose cyclohexane (for oil phase), be 0.5% of cyclohexane (for oil phase) quality by sorbester p17, choose sorbester p17; Sorbester p17 is dissolved in the cyclohexane, obtains containing the cyclohexane of sorbester p17;
Aqueous dibasic potassium phosphate solution (as interior water) is poured in the cyclohexane that contains sorbester p17, stirred, and sonicated 10min, emulsion (w/o type emulsion) obtained;
2) press calcium ion in the calcium nitrate: the mol ratio of phosphoric acid hydrogen radical ion in the dipotassium hydrogen phosphate=1.67: 1, choose calcium nitrate; In calcium nitrate water-soluble (deionized water), obtain the calcium nitrate aqueous solution that the Ca ion concentration is 0.5mol/L;
Mol ratio by calcium ion in the calcium nitrate and shitosan is 5000, chooses shitosan; By shitosan: mass concentration is aqueous acetic acid=2g of 2.5wt%: 100mL, chooses aqueous acetic acid; Shitosan is dissolved in the aqueous acetic acid, obtains the aqueous acetic acid of chitosan-containing; The molecular weight ranges of said shitosan is 300,000～1,000,000;
The aqueous acetic acid of chitosan-containing is splashed in the calcium nitrate aqueous solution, obtain transparent mixed solution (for outer water);
3) press polysorbas20: the mass ratio of mixed solution (outer water)=0.5: 100, choose polysorbas20, subsequent use;
With step 2) mixed solution that obtains pours in the emulsion that step 1) obtains, and stirs 10min, adds polysorbas20, obtains emulsion (W/O/W type emulsion); Emulsion is in 50 ℃ of stirring in water bath reaction 56h;
4) treat that step 3) reaction finishes after, the solution of layering is got the upper strata emulsion layer, behind 50 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol obtains solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres (product) in 50 ℃ of vacuum drying.
The hydroxyapatite/chitosan core-shell nanospheres (product) of preparation is pulverized after SEM observes, and particle diameter is distributed as between the 100-200nm, and is spherical whole, the particle diameter distribution uniform.
Each raw material that the present invention is cited, and the bound of each raw material, interval value, and the bound of technological parameter (like temperature, time etc.), interval value can both realize the present invention, do not enumerate embodiment one by one at this.
Claims (8)
1. the method for an in-situ preparing hydroxyapatite/chitosan core-shell nanospheres is characterized in that it comprises the steps:
1) salt of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion is soluble in water, being made into phosphate anion or phosphoric acid hydrogen radical ion concentration is the solution of 0.3～0.5mol/L; Adding highly basic adjusting pH value then is 11.0～13.0, obtains the aqueous solution of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion;
Press cyclohexane: the volume ratio of the aqueous solution of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion=100～2: 1, choose cyclohexane, be 0.3%～0.5% of cyclohexane quality by surfactant, choose surfactant; Surfactant is dissolved in the cyclohexane, obtains containing the cyclohexane of surfactant;
The aqueous solution of the salt of phosphorus-containing acid ion or phosphoric acid hydrogen radical ion is poured in the cyclohexane that contains surfactant, stirred, and sonicated 5～10min, emulsion obtained;
2) press calcium ion in the calcium salt: the mol ratio of phosphate anion or phosphoric acid hydrogen radical ion=1.5～1.67: 1, choose calcium salt; Calcium salt is soluble in water, obtain the aqueous solution of the calcium salt of Ca ion concentration≤0.5mol/L;
Mol ratio by calcium ion in the calcium salt and shitosan is 0.001～5000, chooses shitosan; By shitosan: mass concentration is aqueous acetic acid=0.5～2g of 1～2.5wt%: 100mL, chooses aqueous acetic acid; Shitosan is dissolved in the aqueous acetic acid, obtains the aqueous acetic acid of chitosan-containing;
The aqueous acetic acid of chitosan-containing is splashed in the aqueous solution of calcium salt, obtain transparent mixed solution;
3) press surfactant: the mass ratio of mixed solution=0.3～0.5: 100, choose surfactant, subsequent use;
With step 2) mixed solution that obtains pours in the emulsion that step 1) obtains, and stirs 5～10min, adds the subsequent use surfactant of step 3), obtains emulsion; Emulsion is in 30 ℃～50 ℃ stirring in water bath reaction 44～56h;
4) treat that step 3) reaction finishes after, the solution of layering is got the upper strata emulsion layer, behind 40～50 ℃ of rotary evaporation cyclohexanes, centrifugal collection solid product, and wash successively with cyclohexane, acetone, absolute ethyl alcohol obtains solids; Solids obtains hydroxyapatite/chitosan core-shell nanospheres in 40～50 ℃ of vacuum drying.
2. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the salt of said phosphorus-containing acid ion is ammonium dihydrogen phosphate (ADP), sodium phosphate or sodium dihydrogen phosphate.
3. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the salt of said phosphoric acid hydrogen radical ion is diammonium hydrogen phosphate, dibastic sodium phosphate, diammonium hydrogen phosphate, dipotassium hydrogen phosphate or sodium hydrogen phosphate.
4. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the said highly basic of step 1) is NaOH or potassium hydroxide.
5. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the said surfactant of step 1) is sorbester p37 or sorbester p17.
6. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: said calcium salt is calcium chloride or calcium nitrate.
7. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the molecular weight ranges of said shitosan is 300,000～1,000,000.
8. the method for a kind of in-situ preparing hydroxyapatite/chitosan core-shell nanospheres according to claim 1 is characterized in that: the said surfactant of step 3) is Tween 80 or polysorbas20.
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| CN106178125A (en) * | 2016-07-20 | 2016-12-07 | 太原理工大学 | A kind of preparation method of nanometer hydroxyapatite chitosan compound microsphere |
| KR102177475B1 (en) * | 2017-07-19 | 2020-11-11 | 단국대학교 천안캠퍼스 산학협력단 | Core-shall structured inorganic-chitosan nanoparticles, and membrane comprising the same |
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| CN111803705B (en) * | 2020-07-24 | 2022-02-25 | 上海济国医疗科技有限公司 | Hydroxyapatite composite material with antibacterial function and preparation method and application thereof |
| CN112744799B (en) * | 2020-12-29 | 2023-04-25 | 江苏集萃智能液晶科技有限公司 | Preparation method and application of carboxylic acid modified hydroxyapatite nanomaterial |
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| EP0719087B1 (en) * | 1994-07-15 | 2000-10-11 | Dow AgroSciences LLC | Preparation of microcapsules |
| CN1389503A (en) * | 2002-07-15 | 2003-01-08 | 浙江大学 | In-situ compounding process of synthesizing nano composite chitosan/hydroxyapatite material |
| CN1966097A (en) * | 2006-11-24 | 2007-05-23 | 武汉理工大学 | Core/shell type polyurethane magnetic compound microsphere, preparation method and use thereof |
| CN101543646A (en) * | 2009-04-30 | 2009-09-30 | 厦门大学 | Method for preparing hydroxyapatite in-situ reinforced chitosan bar material |
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