CN1631973A - Method for preparing bioceramic and biodegradable aliphatic polyester composite materials - Google Patents
Method for preparing bioceramic and biodegradable aliphatic polyester composite materials Download PDFInfo
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- CN1631973A CN1631973A CN 200410011273 CN200410011273A CN1631973A CN 1631973 A CN1631973 A CN 1631973A CN 200410011273 CN200410011273 CN 200410011273 CN 200410011273 A CN200410011273 A CN 200410011273A CN 1631973 A CN1631973 A CN 1631973A
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Abstract
The invention has supplied a method to prepare aliphatic polyester compound material of biological ceramic and biological degradation. Biological ceramic nm/mm particle reacts with glycolic acid in the dehydrating condition of boiling with toluene, or with biological ceramic and glycolic acid in inorganic solvent. By graft on the surface of the biological ceramic particle, acquire the chemical strycture of -biological ceramic, then without water and oxygen, with stannous octoate as initiator, initiate hydroxyl group of glycolic acid loaded with caprolactone, lactide, diglycolide and cyclic ester, acquiring the product of them and nm/mm compound material of copolymer. The biological ceramic modified by glycolic acid and loaded with polyester of surface graft can be used for polyester material directly.
Description
Technical field
The present invention relates to the preparation method of a class biological ceramics and biodegradable aliphatic polyester matrix material.
Background technology
Aliphatic polyester, polylactide (PLA) for example, poly-epsilon-caprolactone (PCL), poly-glycollide (PGA) is a widely used class completely biodegradable material at present.Aliphatic polyester has hypoimmunity and favorable biological degradability, biocompatibility and mechanical strength, so be widely used in biomedicine and field of medicaments, as: fracture fixation material, operating sutures, tissue engineering bracket material, the solid support material of medicament slow release etc.
Biological ceramics (hydroxyapatite, tricalcium phosphate) is good degradable bone alternate material, and untoward reaction takes place in human body hardly, and scleroblast is easier grows on class bone biological ceramics for existing lot of documents report.The synosteosis ability of pure poly(lactic acid) is lower, studies show that in a large number biological ceramics-biodegradable aliphatic polyester matrix material not only can significantly improve the synosteosis ability of material, and the biological ceramics in the component also can be the damaged part of bone high-quality calcium, phosphorus source are provided.
Because nanometer size effect, bigger serface and the strong interfacial bond of disperse phase, nano composite material has more excellent performance than common engineering plastics.Nanometer and polymer blended Composite Melt intensity height, crystallization velocity is fast, melt viscosity is low, therefore improved material injection moulding, extrude the processing characteristics with blowing, the mechanical strength and the modulus of material have also been improved simultaneously, and show the rigidity of inorganics, dimensional stability, thermostability and good barrier properties for gases and flame retardant resistance.United States Patent (USP) U.S.P.4739007 for example; 4618528; 4528235; Disclosed nano composite material in 4874728.
With wide, the out-of-shape of particle diameter distribution in the physics mode bonded nanometer composite inorganic particle/polymer material, size is wayward, and nanoparticle is skewness, easily reunion in polymeric matrix, thereby its application is very restricted.Physics compound biological ceramics-biodegradable aliphatic polyester matrix material is exposed in the physiological environment, do not wait damaged the reparation fully to be convenient to lose prematurely its active strength, losing efficacy mainly betides biological ceramics and polyester interface, and this is owing to lack due to effective adhesion at biological ceramics and polyester two-phase interface.
In order to address these problems, people expect setting up the connection of covalent linkage form between inorganic particulate and polymkeric substance.Biomedical Material Research, Vol.40, p.358-364 reported to be bridge between hydroxyapatite particle and the polymkeric substance with the isocyanic ester in (1998), in the matrix material of preparation, formed the covalent linkage syndeton of hydroxyapatite particle-isocyanic ester-polymer molecular chain.But this method does not satisfy requirement of actual application in fact far away, the toxicity of isocyanic ester is very big, its adding has limited the range of application of matrix material, not enough environmental protection, and the covalent linkage connection amount of the hydroxyapatite particle-isocyanic ester-polymer molecular chain that really obtains in the matrix material that obtains of this method is seldom.
Application number is that the Chinese patent of 200310110048.X discloses a kind of lactic acid modification hydroxyapatite particle surface that utilizes, utilize hydroxyl in institute's load lactic acid molecules to cause polyester monocase then and carry out polymerization, finally obtain the method for the matrix material that hydroxyapatite particle and polyester molecule chain be connected with the chemical bond form.The lactic acid that this method is used is a structural unit of Biodegradable polyester polylactic acid molecule chain, does not have toxic side effect, promptly becomes the part of polyester molecule chain behind the initiated polymerization.The matrix material that this method obtains has the characteristics of high-crystallinity, high strength, high tenacity.
The present invention adopts oxyacetic acid that the biological ceramics particle is carried out surface modification, utilize hydroxyl in the oxyacetic acid molecule of institute's load to cause polyester monocase then and carry out polymerization, finally obtain the matrix material that biological ceramics particle and polyester molecule chain are connected with the chemical bond form.Oxyacetic acid used in the present invention is similarly the friendly material of human body, because hydroxyl is littler than the hydroxyl steric hindrance in the lactic acid molecules in the oxyacetic acid molecule, thereby carries out that next step is easier when causing polyester monocase polyreaction.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of biological ceramics and biodegradable aliphatic polyester matrix material.
Nano meter biomaterial has some properties that exceed conventional biomaterials.Nano meter biomaterial not only the intensity height, toughness is adjustable, and is and good with the biocompatibility and the mechanical compatibility of natural fabric, have excellent biological activity, and can form biological bonding, and present the characteristic of induced tissue growth with natural fabric.The polymkeric substance macromolecular chain will link to each other with the biological ceramics particle by chemical bond in institute of the present invention synthetic novel nano/micron biological ceramics-aliphatic polyester composite material, and inorganic phase particle is uniformly dispersed, and more stable.Thereby finally improve high molecular crystallization velocity, reduce melt viscosity, increase the tensile strength and the Young's modulus of material, improve the easily unstable of degraded of aliphatic polyester materials processing, fundamentally solve the problem of aliphatic polyester processing degradations such as polylactide, and the mechanical property of raising material, be that a class is used good Nano/micron composite biological material.
The present invention at first is the biological ceramics nano/micrometre particle of synthetic surface load oxyacetic acid, to increase the activity of the available hydroxyl of particle surface, these hydroxyls will be as the bridge of inorganic-organic substance, form the active centre with the initiator effect, cause ring-opening polymerization with the effect of aliphatics cyclic ester monomer and obtain Nano/micron biological ceramics biodegradable aliphatic polyester matrix material, and, be by chemical bond phase key chain between the inorganic and organic molecule.
1), the preparation process of the hydroxyapatite nano/micron particle of area load oxyacetic acid is as follows:
The hydroxyapatite that drying is good, tricalcium phosphate or the mixture of the two, the biological ceramics nano/micrometre particle of particle dia scope between 10nm～100 μ m is dispersed in the toluene solvant, add oxyacetic acid again, at 0-80 ℃ of following stirring reaction 0.5-5 hour, form Calcium Glycolate or oligomeric hydroxy lime acetate then at the biological ceramics particle surface; After further reacting 1-48 hour under the methylbenzene azeotropic dehydration conditions, the solid collected by filtration product; Perhaps directly stirred dehydration reaction 0.5～5 hour down at 80～120 ℃ with oxyacetic acid with the biological ceramics particle, collect solid product, solid product repeatedly with chloroform and ethanol alternately washing remove with the biological ceramics particle surface oxyacetic acid of graft reaction not, obtain the modification biological ceramic particle of surface grafting oxyacetic acid behind the filtration drying.
2), the preparation of hydroxyapatite-biodegradable aliphatic polyester matrix material
Selecting biological ceramics-biodegradable aliphatic polyester matrix material is that 0.1～70% biological ceramics nano/micrometre particle and weight percent are that 30～99.9% aliphatic polyester is formed by weight percent, and wherein aliphatic polyester is polylactide, poly-epsilon-caprolactone, gathers binary or ternary random copolymers or segmented copolymer between glycollide or the three kinds of monomers; Adopt four kinds of methods:
(1) in-situ solution polymerization
Modification biological ceramic nano/micron particle is dispersed in refined tetrahydrofuran (THF), toluene, in dimethylbenzene or the dioxane, add aliphatics cyclic ester monomer and stannous octoate catalyst then, the aliphatics cyclic ester monomer is a rac-Lactide, glycollide or 6-caprolactone, initiated polymerization under the anhydrous and oxygen-free condition, the weight percent of monomer and modification biological ceramic particle is 10～99.9%, catalyzer and monomeric weight percent are 2～0.01%, solvent volume is 2 times of monomer weight, polymerization temperature is 60-160 ℃, polymerization time is 12-72 hour, the product dissolution with solvents, go out polymkeric substance with the sinking agent sedimentation, after filtration, washing, vacuum-drying obtains the matrix material of Nano/micron biological ceramics-polymkeric substance.
(2) original position mass polymerization
Dried modification biological ceramic particle and the direct blending dispersion of polymerization single polymerization monomer is even, add stannous octoate catalyst then, initiated polymerization under the anhydrous and oxygen-free condition, the weight percent of monomer and modification biological pottery is 10～99.9%, catalyzer and monomeric weight percent are 2～0.01%, polymerization temperature is 100-160 ℃, and polymerization time is 12-72 hour, obtains the matrix material of Nano/micron biological ceramics-polymkeric substance.
(3) solution blended process
The matrix material that obtains in modification biological ceramic nano/micron particle or (1) and (2) method is dispersed in tetrahydrofuran (THF), trichloromethane, in dimethyl formamide or the toluene, add polylactide, poly-epsilon-caprolactone, binary or ternary random copolymers or segmented copolymer between poly-glycollide or the three kinds of monomers, the weight percent of matrix material and polyester is 10～90%, solvent volume is matrix material and polyester gross weight 10 times, stir sedimentation then, solvent shifts out, solvent evaporation, drying obtains biological ceramics-biodegradable aliphatic polyester matrix material.
(4) melt-blending process
Method with the composite material by adopting melt blending that obtains in modification biological ceramic nano/micron particle or (1) and (2) method, and binary or ternary random copolymers or segmented copolymer between polylactide, poly-epsilon-caprolactone, poly-glycollide or the three kinds of monomers, directly obtain biological ceramics-biodegradable aliphatic polyester matrix material with Banbury mixer or twin screw extruder blend processing, wherein the weight percent of polyester is 10～90% in the matrix material.
Method provided by the invention can be prepared the biological ceramics/aliphatic polyester Nano/micron matrix material of excellent property, by adjusting catalyzer and monomeric ratio, obtain the Nano/micron matrix material of molecular weight of polyesters and each several part adjustable ratio, it is good wherein to be used for the same biocompatibility of oxyacetic acid of modification biological ceramic particle, compares with other surface-modifying agents and does not introduce the unfriendly material that human body repels.Therefore the biological ceramics particle is connected with the chemical bond form with polymer molecular chain in this matrix material, and it is stable to be uniformly dispersed, and can give polymkeric substance and sneak into routine and be difficult to every excellent properties of obtaining in the mode.
Nano grade biological pottery/aliphatic polyester complexes has imitated inorganic and organic composition in the nature bone matrix on forming, its nano level microstructure is similar to nature bone matrix, is that good fracture internal fixing and bone repaired nano meter biomaterial.Therefore, institute of the present invention synthetic new bio pottery/aliphatic polyester Nano/micron matrix material all has very high use value, has wide practical use on medical science and materialogy.
Embodiment
Embodiment 1:
The preparation of the modified hydroxylapatite nanoparticle of surface grafting load oxyacetic acid.In three reaction flasks, (diameter is about 20～50nm) and is dispersed in the 150ml toluene solvant with 15g hydroxyapatite (HA) nanoparticle respectively, add 7.5g respectively, 15g, the oxyacetic acid of 30g (GAc), 60 ℃ of following stirring reactions 3 hours, under the methylbenzene azeotropic dehydration conditions, continue reaction 10 hours then.Product is removed not load oxyacetic acid for 5 times with chloroform and ethanol repetitive scrubbing, and 40 ℃ of following vacuum-drying 48 hours obtains the modified hydroxylapatite nanoparticle of area load oxyacetic acid.Infrared spectra can verify that oxyacetic acid is connected with the chemistry of nanoparticle, and thermogravimetry obtains that the oxyacetic acid charge capacity sees Table 1 on the nanoparticle.
Table 1:
| Numbering | ????HA/GAc ????(g/g) | Oxyacetic acid charge capacity (%Wt) on the modified hydroxylapatite |
| ????1 | ?????2 | ?????9.4 |
| ????2 | ?????1 | ?????18.3 |
| ????3 | ?????0.5 | ?????32.8 |
Embodiment 2:
Among the embodiment 1, replace hydroxyapatite with tricalcium phosphate (TCP), testing sequence is identical with embodiment 1 with method.Obtain content results such as table 2 at tricalcium phosphate surface grafting load oxyacetic acid.
Table 2:
| Numbering | ???TCP/GAc ????(g/g) | Oxyacetic acid charge capacity (%Wt) on the modified phosphate DFP |
| ???1 | ??????2 | ?????10.2 |
| ????2 | ????1 | ????19.4 |
| ????3 | ????0.5 | ????34.8 |
Embodiment 3:
The solvent-free direct preparation of the modified hydroxylapatite nanoparticle of surface grafting load oxyacetic acid.In three reaction flasks, respectively with 15g hydroxyapatite (HA) nanoparticle (diameter is about 20～50nm) and 7.5g, 15g, the oxyacetic acid of 30g (GAc) mixes, stirring reaction is 5 hours under 80～120 ℃ of intensifications.Product is removed not load oxyacetic acid for 5 times with chloroform and ethanol repetitive scrubbing, and 40 ℃ of following vacuum-drying 48 hours obtains the modified hydroxylapatite nanoparticle of area load oxyacetic acid.The oxyacetic acid charge capacity sees Table 3.
Table 3:
| Numbering | ????HA/GAc ????(g/g) | Oxyacetic acid charge capacity (%Wt) on the modified hydroxylapatite |
| ????1 | ??????2 | ?????4.3 |
| ????2 | ??????1 | ?????8.8 |
| ????3 | ??????0.5 | ?????26.4 |
Embodiment 4:
The preparation of modified hydroxylapatite/polylactide matrix material.Polylactide 20g according to needed ratio and number-average molecular weight 95400 is dissolved in the 60ml chloroform solvent with 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%wt), blending dispersion is even, product methyl alcohol sedimentation, washing, obtain nano composite material, its experimental result such as table 4.
Table 4:
| Numbering | Modified hydroxylapatite content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ??1 | ?????0 | ???98.6 | ???64.2 | ???1880 | ???6.6 |
| ????2 | ????5 | ????98.3 | ????69.6 | ????2150 | ????11.2 |
| ????3 | ????8 | ????97.5 | ????76.6 | ????2260 | ????16.5 |
| ????4 | ????15 | ????96.8 | ????78.3 | ????2600 | ????14.1 |
| ????5 | ????25 | ????97.5 | ????70.8 | ????2060 | ????13.4 |
Embodiment 5:
The direct preparation of nanometer hydroxyapatite/polylactide matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the xylene solvent, add 194g respectively, 114g, 54g, 34g, the 14g lactide monomer, solvent volume and monomer weight ratio were 1: 1, add the stannous octoate catalyst of monomer weight 0.01% again, 120 ℃ of following stirring reactions 72 hours.Product methyl alcohol sedimentation, washing, 40 ℃ of following vacuum-drying 48 hours is weighed, and obtains the matrix material of inorganic nano-particle and polymkeric substance, and sample is observed through transmission electron microscope, and test result shows that hydroxyapatite disperses with nanoscale in the material.Infrared spectra, solid state nmr have shown the chemical bond-linking of polymkeric substance and hydroxyapatite particle surface.The molecular weight of various polymkeric substance, productive rate and mechanical property the results are shown in Table 5.
Table 5:
| Numbering | Hydroxyapatite content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ??1 | ????0 | ???96.7 | ????64.2 | ????1880 | ????6.6 |
| ??2 | ????4.7 | ???95.2 | ????83.7 | ????2260 | ????13.6 |
| ??3 | ????9.4 | ???96.6 | ????87.2 | ????2680 | ????15.6 |
| ??4 | ????14.0 | ???96.5 | ????84.6 | ????3310 | ????14.8 |
| ??5 | ????70.2 | ???82.1 | ????67.8 | ????1780 | ????8.7 |
Embodiment 6:
The direct preparation of hydroxyapatite/poly-epsilon-caprolactone nano composite material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the xylene solvent, add 194ml respectively, 114ml, 54ml, 34ml, 14ml 6-caprolactone monomer, solvent volume and monomer weight ratio were 1: 1, add the stannous octoate catalyst of monomer weight 2%, 120 ℃ of following stirring reactions 48 hours.Product is with methyl alcohol (or ethanol) sedimentation, washing, and 40 ℃ of following vacuum-drying 48 hours is weighed, and obtains the matrix material of inorganic nano-particle and polymkeric substance, and the experimental result of various polymer properties sees Table 6.
Table 6:
| Numbering | Hydroxyapatite content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ??1 | ????0 | ??94.7 | ????40.1 | ????351 | ????920 |
| ??2 | ????4.5 | ??96.3 | ????48.5 | ????453 | ????1200 |
| ??3 | ????9.3 | ??95.2 | ????54.8 | ????615 | ????1500 |
| ??4 | ????14.2 | ??93.5 | ????55.4 | ????653 | ????1010 |
| ??5 | ????70.5 | ??87.8 | ????47.6 | ????415 | ????840 |
Embodiment 7:
The direct preparation of hydroxyapatite/poly-glycollide nano composite material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the xylene solvent, add 194g respectively, 114g, 54g, 34g, the 14g glycolide monomer, the stannous octoate catalyst of adding monomer weight 0.5% reacted 72 hours down at 160 ℃, because product dissolving difficulty, therefore, product obtains product through separation and drying, weigh, the compressing tablet film forming is carried out performance test, and various polymer properties experimental results see Table 7.
Table 7:
| Numbering | Hydroxyapatite content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ??1 | ????0 | ??99.5 | ????80.3 | ???2290 | ????2.8 |
| ??2 | ????4.9 | ??98.3 | ????87.4 | ???2550 | ????5.3 |
| ??3 | ????10.1 | ??96.5 | ????99.5 | ???2970 | ????5.8 |
| ???4 | ????15.9 | ??97.3 | ???105.3 | ???3540 | ????4.7 |
| ???5 | ????70.5 | ??88.9 | ???86.4 | ???2660 | ????4.1 |
Embodiment 8:
Hydroxyapatite nano particle with the surface grafting polylactide is the preparation of the nano composite material of expanding material.
(1) under the anhydrous and oxygen-free condition, 25g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4% Wt) is dispersed in the xylene solvent, add the 50g lactide monomer, solvent volume and monomer weight ratio are 2: 1, the stannous octoate catalyst that adds monomer weight 1% again was 120 ℃ of following stirring reactions 72 hours.Product methyl alcohol sedimentation, remove the polymkeric substance that is not grafted to the hydroxyapatite nano particle surface with the chloroform washing repeatedly, 40 ℃ of following vacuum-drying 48 hours, obtain the hydroxyapatite nano particle of surface grafting polylactide, thermal weight loss shows that polylactide wherein accounts for the 32.3%Wt of whole mixture.
(2) hydroxyapatite of the surface grafting polylactide that (1) is obtained (PLA content 30.2%Wt) is as expanding material, polylactide 20g according to needed ratio and number-average molecular weight 95400 is dissolved in 60ml chloroform (or toluene) solvent, blending dispersion is even, product methyl alcohol sedimentation, washing, obtain nano composite material, its experimental result such as table 8.
Table 8:
| Numbering | Expanding material content (%Wt) | HA content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ??1 | ????0 | ????0 | ????97.6 | ????64.2 | ????1880 | ????6.6 |
| ??2 | ????5 | ????3.49 | ????97.3 | ????72.6 | ????2050 | ????13.2 |
| ??3 | ????8 | ????5.58 | ????98.5 | ????83.6 | ????2360 | ????17.5 |
| ??4 | ????15 | ????10.47 | ????95.7 | ????87.3 | ????2800 | ????16.1 |
| ??5 | ????25 | ????17.45 | ????96.3 | ????78.8 | ????2060 | ????14.4 |
Embodiment 9:
Beta-tricalcium phosphate nanometer particle with the surface grafting polylactide is the preparation of the nano composite material of expanding material.
(1) under the anhydrous and oxygen-free condition, 25g modified phosphate DFP nanoparticle (the oxyacetic acid charge capacity is 10.2%Wt) is dispersed in the xylene solvent, add the 50g lactide monomer, solvent volume and monomer weight ratio are 2: 1, the stannous octoate catalyst that adds monomer weight 1% again was 120 ℃ of following stirring reactions 72 hours.Product methyl alcohol sedimentation, remove the polymkeric substance that is not grafted to the beta-tricalcium phosphate nanometer particle surface with the chloroform washing repeatedly, 40 ℃ of following vacuum-drying 48 hours obtains the beta-tricalcium phosphate nanometer particle of surface grafting polylactide, and thermal weight loss shows that polylactide wherein accounts for the 32.1%Wt of whole mixture.
(2) tricalcium phosphate of the surface grafting polylactide that (1) is obtained (PLA content 32.1%Wt) is as expanding material, polylactide 20g according to needed ratio and number-average molecular weight 95400 is dissolved in 60ml chloroform (or toluene) solvent, blending dispersion is even, product methyl alcohol sedimentation, washing, obtain nano composite material, its experimental result such as table 9.
Table 9:
| Numbering | Expanding material content (%Wt) | TCP content (%Wt) | Productive rate (%) | Tensile strength (MPa) | Modulus in tension (MPa) | Elongation at break (%) |
| ???1 | ????0 | ????0 | ????97.6 | ????64.2 | ????1880 | ????6.6 |
| ???2 | ????5 | ????3.4 | ????98.5 | ????73.4 | ????1970 | ????9.2 |
| ???3 | ????8 | ????5.43 | ????97.4 | ????86.4 | ????2260 | ????13.5 |
| ???4 | ????15 | ????10.19 | ????96.8 | ????85.1 | ????2670 | ????15.1 |
| ???5 | ????25 | ????16.98 | ????96.3 | ????71.9 | ????2170 | ????13.4 |
Embodiment 10:
The preparation of nanometer hydroxyapatite-rac-Lactide and 6-caprolactone random copolymers matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the xylene solvent, add 47g lactide monomer and 47ml 6-caprolactone monomer, solvent volume and monomer weight ratio are 1: 1, the stannous octoate catalyst that adds monomer weight 0.1% again was 120 ℃ of following stirring reactions 72 hours.Product methyl alcohol sedimentation, washing, 40 ℃ of following vacuum-drying 48 hours is weighed, and obtains inorganic nano-particle and polyester random copolymers matrix material, and productive rate is 95.4%, and thermal weight loss gets that hydroxyapatite nano particle content is 4.87%Wt in the matrix material.
Embodiment 11:
The preparation of nanometer hydroxyapatite-rac-Lactide and glycollide random copolymers matrix material.Polymerization single polymerization monomer is 70%Wt rac-Lactide and 30Wt% glycollide, other steps are with embodiment 10, obtain inorganic nano-particle and glycollide and rac-Lactide random copolymers matrix material, productive rate is 97.7%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.01%Wt in the matrix material.
Embodiment 12:
The preparation of nanometer hydroxyapatite-6-caprolactone and glycollide random copolymers nano composite material.Polymerization single polymerization monomer is 70%Wt 6-caprolactone monomer and 30% Wt glycollide, other steps are with embodiment 10, obtain inorganic nano-particle and 6-caprolactone and glycollide random copolymers matrix material, productive rate is 96.3%, and thermal weight loss gets that hydroxyapatite nano particle content is 4.83%Wt in the matrix material.
Embodiment 13:
The preparation of nanometer hydroxyapatite-6-caprolactone, rac-Lactide and glycollide ternary atactic copolymer nano composite material.Polymerization single polymerization monomer is 50%Wt 6-caprolactone monomer, 30% Wt rac-Lactide and 20%Wt glycollide, other steps are with embodiment 10, obtain inorganic nano-particle and 6-caprolactone, rac-Lactide and glycollide random copolymers matrix material, productive rate is 96.8%, and thermal weight loss gets that hydroxyapatite nano particle content is 4.94%Wt in the matrix material.
Embodiment 14:
The preparation of nanometer hydroxyapatite-rac-Lactide and 6-caprolactone segmented copolymer matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4 heavy %) is dispersed in the xylene solvent, add the 47g lactide monomer, solvent volume and monomer weight ratio are 1: 1, the stannous octoate catalyst that adds monomer weight 0.1% again was 120 ℃ of following stirring reactions 48 hours.Add the dimethylbenzene dilution, add 47ml 6-caprolactone monomer again, continuation was 120 ℃ of following stirring reactions 48 hours, product methyl alcohol sedimentation, washing, 40 ℃ of following vacuum-drying 48 hours, weigh, obtain inorganic nano-particle and polyester block copolymer matrix material, productive rate is 98.6%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.05%Wt in the matrix material.
Embodiment 15:
The preparation of nanometer hydroxyapatite-rac-Lactide and glycollide segmented copolymer matrix material.Polymerization single polymerization monomer is respectively the glycollide of rac-Lactide and the 30%Wt of 70%Wt, total monomer weight is 94g, adopt the reinforced method of substep, other steps are with embodiment 14, obtain inorganic nano-particle and rac-Lactide and glycollide segmented copolymer matrix material, productive rate is 94.6%, and thermal weight loss gets that hydroxyapatite nano particle content is 4.8%Wt in the matrix material.
Embodiment 16:
The preparation of nanometer hydroxyapatite-6-caprolactone and glycollide block copolymer nano matrix material.Polymerization single polymerization monomer is respectively the glycollide of 6-caprolactone and the 30%Wt of 70%Wt, total monomer weight is 94g, adopt the reinforced method of substep, other steps are with embodiment 14, obtain the nano composite material of inorganic nano-particle and 6-caprolactone and glycollide segmented copolymer, productive rate is 93.7%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.14%Wt in the matrix material.
Embodiment 17:
The preparation of nanometer hydroxyapatite-6-caprolactone, rac-Lactide and glycollide segmented copolymer matrix material.Polymerization single polymerization monomer is respectively 47ml 6-caprolactone, 38g rac-Lactide and 19g glycollide, adopt the reinforced method of substep, other steps are with embodiment 14, obtain inorganic nano-particle and polyester ternary block polymer matrix material, productive rate is 95.6%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.43%Wt in the matrix material.
Embodiment 18:
Nanometer hydroxyapatite-solvent-free the preparation method of polylactide matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the 94g lactide monomer, add the stannous octoate catalyst of monomer weight 0.1% again, stirred bulk reaction 72 hours down at 120 ℃.Product dissolves through toluene, uses the methyl alcohol sedimentation, washing, 40 ℃ of following vacuum-drying 48 hours is weighed, and obtains inorganic nano-particle and polylactide homopolymer matrix material, productive rate is 96.5%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.2%Wt in the matrix material
Embodiment 19:
Nanometer hydroxyapatite-solvent-free the preparation method of polylactide matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the 94g lactide monomer, add the stannous octoate catalyst of monomer weight 0.1% again, stirred bulk reaction 72 hours down at 120 ℃.Product directly obtains inorganic nano-particle and polylactide homopolymer matrix material through pulverizing, and productive rate is 96.8%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.4%Wt in the matrix material.
Embodiment 20:
Nanometer hydroxyapatite-solvent-free the preparation method of 6-caprolactone matrix material.With the rac-Lactide in the 6-caprolactone alternate embodiment 18, other preparation condition is identical, obtains nanometer hydroxyapatite-6-caprolactone matrix material, and productive rate is 97.6%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.2%Wt in the matrix material.
Embodiment 21:
Nanometer hydroxyapatite-solvent-free the preparation method of 6-caprolactone matrix material.With the rac-Lactide in the 6-caprolactone alternate embodiment 18, other preparation condition is identical, obtains nanometer hydroxyapatite-6-caprolactone matrix material, and productive rate is 97.9%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.5%Wt in the matrix material.
Embodiment 22:
Nanometer hydroxyapatite-solvent-free the preparation method of glycollide matrix material.With the rac-Lactide in the glycollide alternate embodiment 18, other preparation condition is identical, obtains nanometer hydroxyapatite-glycollide matrix material, and productive rate is 98.3%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.1%Wt in the matrix material.
Embodiment 23:
Nanometer hydroxyapatite-solvent-free the preparation method of glycollide matrix material.With the rac-Lactide in the glycollide alternate embodiment 19, other preparation condition is identical, obtains nanometer hydroxyapatite-glycollide matrix material, and productive rate is 98.3%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.4%Wt in the matrix material.
Embodiment 24:
Nanometer hydroxyapatite-rac-Lactide and the solvent-free preparation of 6-caprolactone random copolymers matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite nanoparticle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the monomer, monomer is 70%Wt rac-Lactide and 30Wt% 6-caprolactone, total monomer weight is 94g, the stannous octoate catalyst that adds monomer weight 0.1% again was 120 ℃ of following stirring reactions 72 hours.Obtain hydroxyapatite nano particle and rac-Lactide and 6-caprolactone random copolymers matrix material, productive rate is 97.6%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.3%Wt in the matrix material.
Embodiment 25:
Nanometer hydroxyapatite-rac-Lactide and the solvent-free preparation of glycollide random copolymers matrix material.Polymerization single polymerization monomer is 70%Wt rac-Lactide and 30Wt% glycollide, total monomer weight is 94g, other steps are with embodiment 24, obtain inorganic nano-particle and glycollide and rac-Lactide random copolymers matrix material, productive rate is 97.8%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.2%Wt in the matrix material.
Embodiment 26:
The preparation of nanometer hydroxyapatite-6-caprolactone and glycollide random copolymers nano composite material.Polymerization single polymerization monomer is 70%Wt 6-caprolactone monomer and 30%Wt glycollide, other steps are with embodiment 24, obtain inorganic nano-particle and 6-caprolactone and glycollide random copolymers matrix material, productive rate is 97.5%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.3%Wt in the matrix material.
Embodiment 27:
The preparation of nanometer hydroxyapatite-6-caprolactone, rac-Lactide and glycollide ternary atactic copolymer nano composite material.Polymerization single polymerization monomer is 50% Wt 6-caprolactone monomer, 30% Wt rac-Lactide and 20% Wt glycollide, total monomer weight is 94g, other steps are with embodiment 12, obtain inorganic nano-particle and 6-caprolactone, rac-Lactide and glycollide random copolymers matrix material, productive rate is 97.5%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.3% Wt in the matrix material.
Embodiment 28:
The preparation of the modified hydroxylapatite micron particle of surface grafting load oxyacetic acid.(diameter is about 20～50nm), and other reaction is identical with preparation condition, obtains the modified hydroxylapatite micron particle of area load oxyacetic acid with the nanoparticle among hydroxyapatite (HA) micron particle (diameter is about 20～50 μ m) the replacement embodiment 1.Thermogravimetry obtains that the oxyacetic acid charge capacity sees Table 10 on the micron particle.
Table 10:
| Numbering | ????HA/GAc ????(g/g) | Oxyacetic acid charge capacity (%Wt) on the modified hydroxylapatite |
| ????1 | ????2 | ?????6.2 |
| ????2 | ????1 | ?????12.7 |
| ????3 | ????0.5 | ?????30.1 |
At solvent-free bulk reaction down, prepare the modified hydroxylapatite micron particle of area load oxyacetic acid equally.
Embodiment 29:
The solvent-free direct preparation of micron hydroxyapatite/polylactide matrix material.Under the anhydrous and oxygen-free condition, 6g modified hydroxylapatite micron particle (the oxyacetic acid charge capacity is 9.4%Wt) is dispersed in the 97g lactide monomer, add the stannous octoate catalyst of monomer weight 0.1% again, 120 ℃ of following stirring reactions 72 hours.Obtain the matrix material of inorganic micron particle and polylactide, sample is observed through transmission electron microscope, test result shows that hydroxyapatite disperses with micro-meter scale in the material.Productive rate is 97.4%, and thermal weight loss gets that hydroxyapatite nano particle content is 5.2%Wt in the matrix material.
Can prepare the micron hydroxyapatite composite material of poly-epsilon-caprolactone, poly-glycollide with quadrat method, and binary and ternary is random and the micron hydroxyapatite composite material of segmented copolymer between the 6-caprolactone, glycollide, lactide monomer.
Claims (5)
1, a kind of biological ceramics and biodegradable aliphatic polyester matrix material, be made up of the biological ceramics nano/micrometre particle of weight percent 0.1～70% and 30～99.9% aliphatic polyester, wherein aliphatic polyester is binary or ternary random copolymers or the segmented copolymer between polylactide, poly-epsilon-caprolactone, poly-glycollide or the three kinds of monomers.
2, biological ceramics as claimed in claim 1 and biodegradable aliphatic polyester matrix material is characterized in that described biological ceramics is hydroxyapatite, tricalcium phosphate or the mixture of the two.
3, biological ceramics as claimed in claim 1 and biodegradable aliphatic polyester matrix material, the mean diameter scope that it is characterized in that described Nano/micron biological ceramics particle is at 10nm～100 μ m.
4, biological ceramics as claimed in claim 1 and biodegradable aliphatic polyester matrix material, it is characterized in that described monomer rac-Lactide is L-rac-Lactide, D-rac-Lactide, racemize D, L-rac-Lactide, meso D, the mix monomer of wherein one or two or more kinds of L-rac-Lactide.
5, a kind of method for preparing described biological ceramics of claim 1 and biodegradable aliphatic polyester matrix material at first prepares the modification biological ceramic nano/micron particle of area load oxyacetic acid, and preparation process is as follows:
The nano/micrometre particle of hydroxyapatite, tricalcium phosphate or the two the mixture of the particle dia scope that drying is good between 10nm～100 μ m is dispersed in the toluene solvant, add oxyacetic acid again, then at 0-80 ℃ of following stirring reaction 0.5-5 hour, after further reacting 1-48 hour under the methylbenzene azeotropic dehydration conditions, the solid collected by filtration product; Perhaps directly stirred dehydration reaction 0.5～5 hour down at 80～120 ℃ with oxyacetic acid with the biological ceramics particle, collect solid product, solid product repeatedly with chloroform and ethanol alternately washing remove with the biological ceramics particle surface oxyacetic acid of graft reaction not, obtain the modification biological ceramic particle of surface grafting oxyacetic acid behind the filtration drying;
The preparation of biological ceramics-biodegradable aliphatic polyester matrix material, selecting biological ceramics-biodegradable aliphatic polyester matrix material is that 0.1～70% biological ceramics nano/micrometre particle and weight percent are that 30～99.9% aliphatic polyester is formed by weight percent, and wherein aliphatic polyester is polylactide, poly-epsilon-caprolactone, gathers binary or ternary random copolymers or segmented copolymer between glycollide or the three kinds of monomers; Adopt four kinds of methods:
(1) in-situ solution polymerization
Modification biological ceramic nano/micron particle is dispersed in refined tetrahydrofuran (THF), toluene, in dimethylbenzene or the dioxane, add aliphatics cyclic ester monomer and stannous octoate catalyst then, the aliphatics cyclic ester monomer is a rac-Lactide, glycollide or 6-caprolactone, initiated polymerization under the anhydrous and oxygen-free condition, the weight percent of monomer and modification biological ceramic particle is 10～99.9%, catalyzer and monomeric weight percent are 2～0.01%, solvent volume is 2 times of monomer weight, polymerization temperature is 60-160 ℃, polymerization time is 12-72 hour, the product dissolution with solvents, go out polymkeric substance with the sinking agent sedimentation, after filtration, washing, vacuum-drying obtains the matrix material of Nano/micron biological ceramics-polymkeric substance;
(2) original position mass polymerization
Dried modification biological ceramic particle and the direct blending dispersion of polymerization single polymerization monomer is even, add stannous octoate catalyst then, initiated polymerization under the anhydrous and oxygen-free condition, the weight percent of monomer and modification biological pottery is 10～99.9%, catalyzer and monomeric weight percent are 2～0.01%, polymerization temperature is 100-160 ℃, and polymerization time is 12-72 hour, obtains the matrix material of Nano/micron biological ceramics-polymkeric substance;
(3) solution blended process
The matrix material that obtains in modification biological ceramic nano/micron particle or (1) and (2) method is dispersed in tetrahydrofuran (THF), trichloromethane, in dimethyl formamide or the toluene, add polylactide, poly-epsilon-caprolactone, binary or ternary random copolymers or segmented copolymer between poly-glycollide or the three kinds of monomers, the weight percent of matrix material and polyester is 10～90%, solvent volume is matrix material and polyester gross weight 10 times, stir sedimentation then, solvent shifts out, solvent evaporation, drying obtains biological ceramics-biodegradable aliphatic polyester matrix material;
(4) melt-blending process
Method with the composite material by adopting melt blending that obtains in modification biological ceramic nano/micron particle or (1) and (2) method, and binary or ternary random copolymers or segmented copolymer between polylactide, poly-epsilon-caprolactone, poly-glycollide or the three kinds of monomers, directly obtain biological ceramics-biodegradable aliphatic polyester matrix material with Banbury mixer or twin screw extruder blend processing, wherein the weight percent of polyester is 10～90% in the matrix material.
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