CN101584887B - HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method - Google Patents
HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method Download PDFInfo
- Publication number
- CN101584887B CN101584887B CN 200910141569 CN200910141569A CN101584887B CN 101584887 B CN101584887 B CN 101584887B CN 200910141569 CN200910141569 CN 200910141569 CN 200910141569 A CN200910141569 A CN 200910141569A CN 101584887 B CN101584887 B CN 101584887B
- Authority
- CN
- China
- Prior art keywords
- chitosan
- pvp
- polymer network
- interpenetrating polymer
- semi
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Processes Of Treating Macromolecular Substances (AREA)
- Materials For Medical Uses (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
The invention discloses an HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method, comprising: completely mixing in an alkali liquor control system, forming a sol system containing 0.01-50% by mass of PVP; aging and washing to obtain an HA sol, mixing with a mixed solution with the mass ratio of PVP : chitosan solute being 0.1-2.5 : 1, feeding the mixed solution with the massratio of mixed solution solute : HA sol being 0.1-9 : 1 into a high speed dispersion machine for mixing cross link; injecting into a die, processing to obtain the frame. The prepared HA is evenly dis persed in the chitosan/PVP semi-interpenetrating polymer network substrate, forms an effective bonding with the substrate and presents direction arrangement so as to realize the effective compounding of the nano hydroxyapatite and the substrate, solve the problem of chitosan material and improve the frame functional performance.
Description
Technical field
The present invention relates to artificial bone repair materials technical field, specifically refer to the preparation method of a kind of HA (nanometer hydroxyapatite)/chitosan/PVP (polyvinylpyrrolidone) semi-interpenetrating polymer network frame.
Background technology
Growing along with bone defect repair demand in domestic and international clinical medicine, because traditional bone renovating material exists some problems, organizational project develops rapidly, its ultimate principle is that the normal tissue cell with cultured and amplified in vitro is adsorbed in that a kind of biocompatibility is good, on the bio-carrier that can be absorbed by body, form complex, with cell carrier complex implanting to human body tissue, lesions position, cell forms respective organization and the organ with morphology and function at carrier in by the process of body degraded and absorbed, reaches the purpose of repairing wound and Reconstruction of The Function.
Chitosan (being called for short CS) is a kind of natural biodegradable polysaccharide, its catabolite is glucosamine, to human body and organize nontoxic, harmless, have natural pharmaceutically active, anti-tumor activity, antiinflammation, can accelerate wound healing, thereby be widely used in bone tissue engineering stent material.But chitosan lacks bone bonding biological activity, and the mechanical property when using separately is not ideal enough, as large in fragility, poor toughness, and degraded is slow, and hydrophilic is also good not as collagen.therefore, in order to improve the performance of chitosan, Many researchers is by adopting the compound method of chitosan and hydroxy apatite powder, as Sun Kaiying, Sun Weibin, storage is grown into forest, Deng. the impact of nanometer hydroxyapatite-Chitosan Composites on cell adhesion. clinical stomatology magazine, 2007, 23 (3): 150-153, this article is with Preparation of Nano-hydroxyapatite by Sol-gel Method, then hydroxy apatite powder fully is mixed in 2% chitosan acetic acid solution, freeze-drying prepares nanometer hydroxyapatite-Chitosan Composites, result shows the space 6 square crystal structures of the crystal structure conformance with standard hydroxyapatite of the HA of sol-gel process preparation and nHA, and cell adheres to composite material surface with a plurality of projections, and has a good extended configuration.although these methods have been improved bone bonding biological activity and the mechanical property of simple chitosan to a certain extent, but because hydroxyapatite is compound with matrixes such as powder type and chitosans, thereby hydroxyapatite is easy to reunite, in fact be difficult to Uniform Dispersion and and chitosan basal body between can't form effective bonding, hydroapatite particles can only be loose be distributed in the chitosan framework, can not effectively realize the effectively compound of nanometer hydroxyapatite and chitosan, also be difficult to really solve the chitosan material Main Problems, thereby limit its function and in the application of biomedical sector.
The research discovery, polyvinylpyrrolidone is a kind of high molecular weight water soluble polymer, has surface activity, complexing, chemical stability and excellent physiological compatibility, it is a kind of more ripe multiduty medical auxiliary materials and is used for disinfection sanitizer.The composite of polyvinylpyrrolidone and chitosan had some reports in recent years.Sionkowska.A, Wisniewski.M, Skopinska.J, Deng. the impact of ultra-vioket radiation on chitosan/PVP blend mechanical performance. the degraded of polymer and stability (The influenceof UV irradiation on the mechanical properties of chitosan/poly (vinylpyrrolidone) blends, Polymer Degradation and Stability), 2005, 88 (2): 261-267, this article is with chitosan, PVP and chitosan/PVP blend before and after the ultra-vioket radiation machinery and the variation of surface nature be studied, result shows that the engineering properties of blend is (as fracture strength, elongation at break and Young's modulus) be subjected to significantly the impact of ultra-vioket radiation, but the intensity of variation of these character of blend is less than the intensity of variation of pure chitosan, and determined by irradiation time and sample composition.Mallika.P.Himabindu.A, Shailaja.D. the improvement of modified biological material chitosan and physicochemical properties thereof. polymer applications science journal (Modification of chitosan towards abiomaterial with improved physico-chemical properties, AppliedPolymer Science), 2006,101 (1): 63-69, this article adopts three kinds of methods with PVP, CS to be carried out modification, namely mix by the ratio that changes chitosan and PVP, graft copolymerization and free yl induction are crosslinked.Research is tied and is shown, blending and modifying has strengthened intensity, toughness, glass transition temperature and the heat stability of dry film.Above-mentioned chitosan/PVP intermingling material engineering properties and stable aspect all improve to some extent than chitosan, but the relevant chitosan/practical application of PVP intermingling material aspect bone tissue engineering stent material there is no any report.
In addition, semi interpenetration polymer network material begins to be applied to technical field of biological material owing to having unique performance, semi-interpenetrating polymer network refers in two kinds of polymer that consist of interpenetrating networks, it is crosslinked that a kind of polymer is only arranged, another kind of polymer is that line style is noncrosslinking, exist physics to run through between network and segment, and almost without chemical bond.It can have the excellent properties of general physical blending, grafting, block polymer simultaneously.Yet this technology is not used for the preparation of chitosan/PVP semi-interpenetrating polymer network bone tissue engineering scaffold.If hydroxyapatite is dispersed in the semi-interpenetrating polymer network matrix of chitosan/PVP, and present aligning and forming effective bonding with matrix of hydroapatite particles in this matrix, be expected to realize the improvement of the performances such as stability, hydrophilic of timbering material on the basis that solves existing chitosan/hydroxyapatite scaffold existing issue.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part, a kind of crystallization degree is controlled by researching and developing, good dispersion, can have with macromolecular material the nano hydroxyapatite colloidal sols of the particle direction-arrangement of stable bonding, above-mentioned colloidal sol be dispersed in the semi-interpenetrating polymer network matrix of chitosan/PVP and form effective bonding with matrix, thereby the preparation method of a kind of HA (nanometer hydroxyapatite)/chitosan/PVP (polyvinylpyrrolidone) semi-interpenetrating polymer network frame is provided.
Realization the present invention seeks to be achieved by the following measures.
The preparation method of a kind of HA (nanometer hydroxyapatite)/chitosan/PVP (polyvinylpyrrolidone) semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: HA is the preparation of nano hydroxyapatite colloidal sols
(1) be that polyvinylpyrrolidone is simultaneously as template, dispersant and modifier take PVP;
(2) phosphate solution of the preparation calcium salt of 0.01～3mol/L and 0.006～1.8mol/L or prepare the calcium salt soln of 0.01～3mol/L and the phosphoric acid of 0.006～1.8mol/L;
(3) adopt high speed dispersor, in the alkali liquor hierarchy of control, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol; In this HA sol system, calcium phosphorus mol ratio reaches 1.6～1.7: 1, and PVP content is 0.01～50% by mass percentage;
Step 2: the ageing of HA colloidal sol
Then the ageing at least 24 hours at the temperature of 20～100 ℃ of above-mentioned colloidal sol fully washs with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) with acetum preparation mass percent be 1%～4% chitosan solution;
(2) in PVP: the mass ratio of chitosan solute is that 0.1～2.5: 1 ratio joins PVP the blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) HA of step 2 mixed with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopt high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid: the mass ratio of HA colloidal sol is 0.1～9: 1;
(4) add chitosan crosslinked dose to stir at normal temperatures crosslinked 12h at least in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, chitosan crosslinked agent content is 0.01～1% of mixed liquor by mass percentage;
(5) decompression of the mixed liquor after above-mentioned (4) crosslinked is removed injection model after bubble, and be placed in ultra cold storage freezer freezing at least 24 hours, then change in freezer dryer lyophilization at least 24 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) at first HA/ chitosan/PVP semi-interpenetrating polymer network frame was soaked 1～3 hour with alkali liquor or buffer solution, and then be dipped to few 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into ultra cold storage freezer freezing at least 24 hours, and changes in freezer dryer lyophilization at least 24 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
In order to realize better the present invention, the described mixing of materials of step 1 (3), adding of PVP has following dual mode, selects a use:
(1) PVP is joined in calcium salt or phosphate solution or phosphoric acid, or join in the mixed solution of calcium salt and phosphate or phosphoric acid;
(2) first prepare the PVP aqueous solution, then prepare calcium salt and phosphate or phosphoric acid solution with the polyvinylpyrrolidone aqueous solution.
Described calcium salt is lime nitrate or calcium hydroxide; Phosphate adopts diammonium phosphate, sodium hydrogen phosphate or dipotassium hydrogen phosphate.
The described ageing of step 2 has following dual mode, selects a use:
(1) nano hydroxyapatite colloidal sols is placed ageing naturally;
(2) nano hydroxyapatite colloidal sols is moved into the ageing of heating evaporation reflux.
Described alkali liquor hierarchy of control pH value is greater than 10.5; Described alkali liquor is ammonia, sodium hydroxide or potassium hydroxide solution.
Described buffer solution is sodium hydrogen phosphate or sodium bicarbonate solution.
The velocity interval of described high speed dispersor is 100～8000 rev/mins.
It is described that to adopt the type of polyvinylpyrrolidone be K15, K30, K60 or K90.
In described ultra cold storage freezer, freezing temperature range is-5 ℃～-80 ℃.
Described chitosan crosslinked dose is glutaraldehyde, Biformyl, Polyethylene Glycol bisglycidyl ether or polyglycerol triglycidyl ether.
The present invention has following outstanding advantage compared with prior art:
1, the present invention arrives the technology of preparing successful Application of semi-interpenetrating polymer network frame in the preparation of HA/ chitosan/PVP semi-interpenetrating polymer network frame first, function served as bridge by PVP, make hydroapatite particles good dispersion in chitosan/PVP semi-interpenetrating polymer network matrix, and and matrix between formed effective, stable bonding, and hydroxyapatite granule in chitosan basal body presents and aligns, thereby realizes the effectively compound of nanometer hydroxyapatite and chitosan/PVP matrix on 26S Proteasome Structure and Function.
2, the present invention adopts form and the chitosan-based bluk recombination with hydroxyapatite colloidal sols, overcome in prior art with the hydroxyapatite powder form, adopt standard machinery to mix to exist between hydroxyapatite and chitosan basal body in the nano hydroxylapatite granule/chitosan stent of preparation and can't form effective bonding, and hydroapatite particles can only be loose be distributed in the chitosan framework, can not realize the effective compound problem of nanometer hydroxyapatite and chitosan; Effectively solve simultaneously chitosan and lacked the bioactive problem of bone bonding.
The excellent properties that 3, can have simultaneously general physical blending, grafting, block polymer due to semi-interpenetrating polymer network, thereby the HA/ chitosan of the present invention's preparation/PVP semi-interpenetrating polymer network bone tissue engineering scaffold, solved the dissatisfactory problem of mechanical property when chitosan uses separately, improved the hydrophilic of chitosan, strengthen the stability of chitosan, also solved to a certain extent the slow problem of degradation of chitosan.
4, the present invention adopts and has good dispersion stabilization, good biocompatibility and the polyvinylpyrrolidone of physiological security are as template, dispersant and modifier, simultaneously form semi-interpenetrating polymer network as matrix with chitosan, be unlikely to the problem of the physiology toxicity that causes when improving material property.
5. preparation technology of the present invention is simple, and is simple to operation, is easy to apply.
The specific embodiment
Below in conjunction with embodiment, the present invention is described in further detail, but embodiment is not limited in this.
Embodiment 1
The preparation method of a kind of HA/ chitosan/PVP semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: the preparation of HA colloidal sol
(1) take polyvinylpyrrolidone (PVP K15) simultaneously as template, dispersant, modifier;
(2) use the deionized water preparation to contain lime nitrate 0.01mol/L, then the solution of diammonium phosphate 0.006mol/L join 0.1g PVP K15 fully dissolving in above-mentioned calcium nitrate solution;
(3) adopt the high speed dispersor of 100 rev/mins, be under 10.6 conditions at ammonia hierarchy of control pH value, the material of above-mentioned (1), (2) is fully mixed, form nano hydroxyapatite colloidal sols, make that in this nano hydroxyapatite colloidal sols system, calcium phosphorus mol ratio reaches 1.6: 1, polyvinylpyrrolidone content is 0.01% by mass percentage;
Step 2: the ageing of HA colloidal sol
Above-mentioned HA colloidal sol is placed ageing 24 hours naturally under room temperature (20 ℃), then fully wash with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be that 2% acetum preparation mass percent is 1% chitosan solution with mass percent concentration;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 0.1: 1 joins PVP K15 the blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) the HA colloidal sol with step 2 mixes with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopts high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid with the speed of 100 rev/mins: the mass ratio of HA colloidal sol is 0.1: 1;
(4) add glutaraldehyde solution to stir at normal temperatures crosslinked 12h in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, the glutaraldehyde cross-linking agent content is 0.01% of mixed liquor by mass percentage;
(5) the mixed liquor decompression of the crosslinked rear HA/ chitosan/PVP of above-mentioned (4) is removed in the ultra cold storage freezer that injection model after bubble is placed on-5 ℃ freezing 24 hours, then change in freezer dryer lyophilization over to 24 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be at first that 0.5% ammonia soaked 1 hour with HA/ chitosan/PVP semi-interpenetrating polymer network frame mass percent concentration, and then soaked 6 hours with deionized water, change water per half an hour one time;
(2) timbering material after cleaning is put back to model, again puts into the ultra cold storage freezer of-5 ℃ after freezing 24 hours, changes in freezer dryer lyophilization over to 24 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
Embodiment 2
The preparation method of a kind of HA/ chitosan/PVP semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: the preparation of HA colloidal sol
(1) take PVP K30 simultaneously as template, dispersant, modifier;
(2) preparation of the PVP K30 aqueous solution of service property (quality) percentage ratio 0.5% contains lime nitrate 0.1mol/L, the solution of sodium hydrogen phosphate 0.06mol/L;
(3) adopt the high speed dispersor of 1000 rev/mins, be under 11 condition at sodium hydroxide hierarchy of control pH value, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol, make that in this HA sol system, calcium phosphorus mol ratio reaches 1.65: 1, PVP content is 0.5% by mass percentage;
Step 2: the ageing of HA colloidal sol
Above-mentioned HA colloidal sol is moved into the heating evaporation reflux, in 50 ℃ of evaporation backflows ageing in 36 hours, then fully wash with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be that 2% acetum preparation mass percent is 1.5% chitosan solution with mass percent concentration;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 0.25: 1 joins PVP K30 the blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) the HA colloidal sol with step 2 mixes with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopts high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid with the speed of 1000 rev/mins: the mass ratio of HA colloidal sol is 0.25: 1;
(4) add glyoxal solution to stir at normal temperatures crosslinked 12h in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, the Biformyl content of crosslinking agent is 0.05% of mixed liquor by mass percentage;
(5) the mixed liquor decompression of the crosslinked rear HA/ chitosan/PVP of above-mentioned (4) is removed in the ultra cold storage freezer that injection model after bubble is placed on-10 ℃ freezing 24 hours, then change in freezer dryer lyophilization over to 36 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be at first that the sodium hydroxide solution of 0.005mol/L soaked 2 hours with HA/ chitosan/PVP semi-interpenetrating polymer network frame mass percent concentration, and then soaked 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into the ultra cold storage freezer of-10 ℃ after freezing 24 hours, changes in freezer dryer lyophilization over to 36 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
Embodiment 3
The preparation method of a kind of HA/ chitosan/PVP semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: the preparation of HA colloidal sol
(1) take PVP K60 simultaneously as template, dispersant, modifier;
(2) preparation of the PVP K60 aqueous solution of service property (quality) percentage ratio 5% contains lime nitrate 0.5mol/L, the solution of dipotassium hydrogen phosphate 0.3mol/L;
(3) adopt the high speed dispersor of 2000 rev/mins, be under 11.5 conditions at potassium hydroxide hierarchy of control pH value, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol, make that in this HA sol system, calcium phosphorus mol ratio reaches 1.67: 1, PVP content is 5% by mass percentage;
Step 2: the ageing of HA colloidal sol
Above-mentioned hydroxyapatite colloidal sols is moved into the heating evaporation reflux, in 70 ℃ of evaporation backflows ageing in 48 hours, then fully wash with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be that 2% acetum preparation mass percent is 2% chitosan solution with mass percent concentration;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 0.65: 1 joins PVP (K60) blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) the HA colloidal sol with step 2 mixes with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopts high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid with the speed of 2000 rev/mins: the mass ratio of HA colloidal sol is 1: 1;
(4) add Polyethylene Glycol bisglycidyl ethereal solution to stir at normal temperatures crosslinked 24h in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, Polyethylene Glycol bisglycidyl ether content of crosslinking agent is 0.1% of mixed liquor by mass percentage;
(5) the mixed liquor decompression of the crosslinked rear HA/ chitosan/PVP of above-mentioned (4) is removed in the ultra cold storage freezer that injection model after bubble is placed on-20 ℃ freezing 24 hours, then change in freezer dryer lyophilization over to 48 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) at first the potassium hydroxide solution of HA/ chitosan/PVP semi-interpenetrating polymer network frame with 0.5mol/L soaked 3 hours, and then soaked 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into the ultra cold storage freezer of-20 ℃ after freezing 24 hours, changes in freezer dryer lyophilization over to 48 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
Embodiment 4
The preparation method of a kind of HA/ chitosan/PVP semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: the preparation of HA colloidal sol
(1) take PVP K90 simultaneously as template, dispersant, modifier;
(2) use the deionized water preparation to contain calcium hydroxide 1mol/L, then the solution of phosphoric acid 0.6mol/L join 5g PVP K90 respectively fully dissolving in above-mentioned lime nitrate and phosphoric acid;
(3) adopt the high speed dispersor of 5000 rev/mins, be under 12 condition at potassium hydroxide hierarchy of control pH value, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol, make that in this HA sol system, calcium phosphorus mol ratio reaches 1.67: 1, PVP content is 10% by mass percentage;
Step 2: the ageing of HA colloidal sol
Above-mentioned hydroxyapatite colloidal sols is moved into the heating evaporation reflux, in 90 ℃ of evaporation backflows ageing in 60 hours, then fully wash with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be that 2% acetum preparation mass percent is 3% chitosan solution with mass percent concentration;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 1: 1 joins PVP (K90) blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(the 3 HA colloidal sols with step 2 mix with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopt high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid with the speed of 5000 rev/mins: the mass ratio of HA colloidal sol is 4: 1;
(4) add polyglycerol three-glycidyl ethereal solution to stir at normal temperatures crosslinked 24h in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, polyglycerol triglycidyl ether content of crosslinking agent is 0.5% of mixed liquor by mass percentage;
(5) the mixed liquor decompression of the crosslinked rear HA/ chitosan/PVP of above-mentioned (4) is removed in the ultra cold storage freezer that injection model after bubble is placed on-65 ℃ freezing 24 hours, then change in freezer dryer lyophilization over to 48 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) at first the sodium bicarbonate solution of HA/ chitosan/PVP semi-interpenetrating polymer network frame with 1mol/L soaked 3 hours, and then soaked 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into the ultra cold storage freezer of-65 ℃ after freezing 24 hours, changes in freezer dryer lyophilization over to 48 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
Embodiment 5
The preparation method of a kind of HA/ chitosan/PVP semi-interpenetrating polymer network frame comprises the following steps and process conditions:
Step 1: the preparation of HA colloidal sol
(1) take PVP K90 simultaneously as template, dispersant, modifier;
(2) use the deionized water preparation to contain calcium hydroxide 3mol/L, then the solution of dipotassium hydrogen phosphate 1.8mol/L join 50g PVP K90 fully dissolving in above-mentioned dipotassium hydrogen phosphate;
(3) adopt the high speed dispersor of 8000 rev/mins, be under 12 conditions at ammonia hierarchy of control pH value, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol, make that in this HA sol system, calcium phosphorus mol ratio reaches 1.7: 1, PVP content is 50% by mass percentage;
Step 2: the ageing of HA colloidal sol
Above-mentioned colloidal sol is placed at the temperature of 100 ℃, and then ageing 48 hours fully washs colloidal sol with deionized water, then fully washs with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) be that 2% acetum preparation mass percent is 4% chitosan solution with mass percent concentration;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 2.5: 1 joins PVP K90 the blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) the HA colloidal sol with step 2 mixes with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopts high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid with the speed of 8000 rev/mins: the mass ratio of HA colloidal sol is 9: 1;
(4) add glutaraldehyde solution to stir at normal temperatures crosslinked 12h in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, the glutaraldehyde cross-linking agent content is 1% of mixed liquor by mass percentage;
(5) the mixed liquor decompression of the crosslinked rear HA/ chitosan/PVP of above-mentioned (4) is removed in the ultra cold storage freezer that injection model after bubble is placed on-80 ℃ freezing 24 hours, then change in freezer dryer lyophilization over to 48 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) at first the disodium phosphate soln of HA/ chitosan/PVP semi-interpenetrating polymer network frame with 0.05mol/L soaked 3 hours, and then soaked 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into the ultra cold storage freezer of-80 ℃ after freezing 24 hours, changes in freezer dryer lyophilization over to 48 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
Claims (7)
1.HA/ the preparation method of chitosan/PVP semi-interpenetrating polymer network frame is characterized in that comprising the following steps and process conditions:
Step 1: HA is the preparation of nano hydroxyapatite colloidal sols
(1) be that polyvinylpyrrolidone is simultaneously as template, dispersant and modifier take PVP;
(2) phosphate solution of the preparation calcium salt of 0.01～3mol/L and 0.006～1.8mol/L or prepare the calcium salt soln of 0.01～3mol/L and the phosphoric acid of 0.006～1.8mol/L;
Described calcium salt is lime nitrate or calcium hydroxide; Phosphate adopts diammonium phosphate, sodium hydrogen phosphate or dipotassium hydrogen phosphate;
(3) adopt high speed dispersor, in the alkali liquor hierarchy of control, the material of above-mentioned (1), (2) is fully mixed, form HA colloidal sol; In this HA sol system, calcium phosphorus mol ratio reaches 1.6～1.7:1, and PVP content is 0.01%～50% by mass percentage; Described alkali liquor hierarchy of control pH value is greater than 10.5; Described alkali liquor is ammonia, sodium hydroxide or potassium hydroxide solution;
Step 2: the ageing of HA colloidal sol
Then the ageing at least 24 hours at the temperature of 20～100 ℃ of above-mentioned colloidal sol fully washs with deionized water the HA colloidal sol that colloidal sol obtains particle direction-arrangement;
Step 3: the molding of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) with acetum preparation mass percent be 1%～4% chitosan solution;
(2) in PVP: the mass ratio of chitosan solute is that the ratio of 0.1～2.5:1 joins PVP the blended liquid that obtains chitosan/PVP after fully mixing in the chitosan solution of above-mentioned (1);
(3) the HA colloidal sol of step 2 mixed with the blended liquid of the chitosan/PVP of above-mentioned (2) and adopt high speed dispersor to disperse to obtain the mixed liquor of HA/ chitosan/PVP, the wherein solute of the chitosan of above-mentioned (2)/PVP blended liquid: the mass ratio of HA colloidal sol is 0.1～9:1;
(4) add chitosan crosslinked dose to stir at normal temperatures crosslinked 12h at least in the mixed liquor of the HA/ of above-mentioned (3) chitosan/PVP, chitosan crosslinked agent content is 0.01%～1% of mixed liquor by mass percentage; Described chitosan crosslinked dose is glutaraldehyde, Biformyl, Polyethylene Glycol bisglycidyl ether or polyglycerol triglycidyl ether;
(5) decompression of the mixed liquor after above-mentioned (4) crosslinked is removed injection model after bubble, and be placed in ultra cold storage freezer freezing at least 24 hours, then change in freezer dryer lyophilization at least 24 hours, and namely obtained HA/ chitosan/PVP semi-interpenetrating polymer network frame;
Step 4: the post processing of HA/ chitosan/PVP semi-interpenetrating polymer network frame
(1) at first HA/ chitosan/PVP semi-interpenetrating polymer network frame was soaked 1～3 hour with alkali liquor or buffer solution, and then be dipped to few 6 hours with deionized water, change one time water per at least half an hour;
(2) timbering material after cleaning is put back to model, again puts into ultra cold storage freezer freezing at least 24 hours, and changes in freezer dryer lyophilization at least 24 hours, obtains at last HA/ chitosan/PVP semi-interpenetrating polymer network frame.
2. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame, is characterized in that the described mixing of materials of step 1 (3), and adding of polyvinylpyrrolidone has following dual mode, selects a use:
(1) PVP is joined in calcium salt or phosphate solution or phosphoric acid, or join in the mixed solution of calcium salt and phosphate or phosphoric acid;
(2) first prepare the PVP aqueous solution, then prepare calcium salt and phosphate or phosphoric acid solution with the PVP aqueous solution.
3. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame is characterized in that the described ageing of step 2 has following dual mode, selects a use:
(1) nano hydroxyapatite colloidal sols is placed ageing naturally;
(2) nano hydroxyapatite colloidal sols is moved into the ageing of heating evaporation reflux.
4. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame, is characterized in that described buffer solution is sodium hydrogen phosphate or sodium bicarbonate solution.
5. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame, the velocity interval that it is characterized in that described high speed dispersor is 100～8000 rev/mins.
6. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame is characterized in that described to adopt the type of polyvinylpyrrolidone be K15, K30, K60 or K90.
7. the preparation method of HA/ chitosan according to claim 1/PVP semi-interpenetrating polymer network frame, is characterized in that temperature range freezing in described ultra cold storage freezer is-5 ℃～-80 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910141569 CN101584887B (en) | 2008-07-31 | 2009-05-31 | HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810029861 | 2008-07-31 | ||
| CN200810029861.7 | 2008-07-31 | ||
| CN 200910141569 CN101584887B (en) | 2008-07-31 | 2009-05-31 | HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101584887A CN101584887A (en) | 2009-11-25 |
| CN101584887B true CN101584887B (en) | 2013-06-12 |
Family
ID=41369450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910141569 Expired - Fee Related CN101584887B (en) | 2008-07-31 | 2009-05-31 | HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101584887B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102888027B (en) * | 2012-09-26 | 2014-10-08 | 华南理工大学 | Bacterial cellulose/collagen-chitosan composite material and preparation method thereof |
| CN106333923A (en) * | 2016-10-13 | 2017-01-18 | 文山学院 | Panax notoginseng saponins sustained-release gel and preparation method thereof |
| CN107050524A (en) * | 2016-12-23 | 2017-08-18 | 江南大学 | A kind of preparation method of novel antibacterial composite biological material |
| PL235354B1 (en) * | 2018-01-30 | 2020-06-29 | Politechnika Krakowska Im Tadeusza Kosciuszki | Method for obtaining bioactive polymer-ceramic composite biomaterial |
| CN111184907A (en) * | 2018-11-15 | 2020-05-22 | 江汉大学 | Preparation method of ordered porous nerve conduit material |
| CN110354818B (en) * | 2019-08-05 | 2020-07-03 | 泰州禾益新材料科技有限公司 | Hydroxyapatite-based composite material for adsorbing arsenic and fluorine in water and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389512A (en) * | 2002-06-21 | 2003-01-08 | 华南理工大学 | Bioactive nano composite PVA-hydroxyapatite aquagel and its prepn. |
| CN1799647A (en) * | 2005-12-13 | 2006-07-12 | 天津大学 | Nanometer hydroxyapatite/chitosan/gelatin porous scaffold material and preparation method thereof |
| CN100341776C (en) * | 2006-02-22 | 2007-10-10 | 福建师范大学 | Method for prenaring spherical hydroxy-apatite nano crystal |
-
2009
- 2009-05-31 CN CN 200910141569 patent/CN101584887B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389512A (en) * | 2002-06-21 | 2003-01-08 | 华南理工大学 | Bioactive nano composite PVA-hydroxyapatite aquagel and its prepn. |
| CN1799647A (en) * | 2005-12-13 | 2006-07-12 | 天津大学 | Nanometer hydroxyapatite/chitosan/gelatin porous scaffold material and preparation method thereof |
| CN100341776C (en) * | 2006-02-22 | 2007-10-10 | 福建师范大学 | Method for prenaring spherical hydroxy-apatite nano crystal |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101584887A (en) | 2009-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101584887B (en) | HA/chitosan/PVP semi-interpenetrating polymer network frame preparing method | |
| CN100563727C (en) | The preparation method of a kind of nanometer hydroxyapatite/fibroin-chitosan compound rest | |
| Sethi et al. | A review on chitosan-gelatin nanocomposites: Synthesis, characterization and biomedical applications | |
| Ma et al. | Synthesis and characterization of injectable self-healing hydrogels based on oxidized alginate-hybrid-hydroxyapatite nanoparticles and carboxymethyl chitosan | |
| CN103446621B (en) | Preparation method of nano-silver-containing sodium alginate based antibacterial medical dressing | |
| WO2018072679A1 (en) | Biomimetic biomineralized artificial bone repair material and preparation method therefor and use thereof | |
| CN102321271B (en) | Preparation method for chitosan-based porous scaffolds with biological activity | |
| CN101098718A (en) | Chitosan compositions | |
| CN103386150B (en) | Preparation method and application of glucomannan/chitosan composite membrane for conducting tissue regeneration | |
| CN101554493B (en) | Method for preparing nano hydroxyapatite/collagen scaffold with directionally arranged particles | |
| CN112023120B (en) | Injectable pre-filled bone repair particle and preparation method and application thereof | |
| CN106188609B (en) | A kind of L-lysine modified hyaluronic acid derivative hydrogel and preparation method thereof | |
| EP2970000A1 (en) | Calcium phosphate cement compositions that set into high strength porous structures | |
| CN101270192B (en) | Polyvinyl alcohol gel rubber system and preparation method thereof | |
| CN101612419B (en) | Preparation method of HA/collagen/PVP semi-interpenetrating polymer network scaffold | |
| Benedini et al. | Assessment of synergistic interactions on self-assembled sodium alginate/nano-hydroxyapatite composites: to the conception of new bone tissue dressings | |
| CN101928355B (en) | Aminated alginic acid and preparation method thereof | |
| CN103656756B (en) | Nano-hydroxyapatite/silk fibroin composite membrane material and preparation method thereof | |
| CN101352585B (en) | Method for preparing directionally arranged nano hydroxylapatite granule/chitosan stent | |
| CN105148322A (en) | Injectable hydrogel and method for preparing same | |
| CN104707179A (en) | Oil-soluble/water-soluble organic-inorganic three-phase porous micro-nanometer composite bone repair material | |
| Ghorbani et al. | Dual-crosslinked in-situ forming alginate/silk fibroin hydrogel with potential for bone tissue engineering | |
| KR100889593B1 (en) | Hybrid Composite of Biopolymers and Bioceramics, and Method for Preparing the Same | |
| CN111249523B (en) | Bone-like composite material support and preparation method thereof | |
| CN101590293B (en) | Method for preparing HA/collagen/chitosan interpenetrating polymer network bracket |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130612 Termination date: 20170531 |