CN1314462C - Degradable biomedicine composite material in nanometer structure and its prepn process - Google Patents
Degradable biomedicine composite material in nanometer structure and its prepn process Download PDFInfo
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- CN1314462C CN1314462C CNB2005100496525A CN200510049652A CN1314462C CN 1314462 C CN1314462 C CN 1314462C CN B2005100496525 A CNB2005100496525 A CN B2005100496525A CN 200510049652 A CN200510049652 A CN 200510049652A CN 1314462 C CN1314462 C CN 1314462C
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 95
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- Materials For Medical Uses (AREA)
Abstract
The present invention discloses nanometer structured degradable biomedical composite material and a preparing method thereof. The composite material is prepared by the composition of nanometer structured calcium phosphate powder and degradable polymers, wherein the nanometer structured calcium phosphate powder is composed of any two of alpha phase tricalcium phosphate, beta phase tricalcium phosphate and apatite. The composite material preparing method comprises: the nanometer structured calcium phosphate powder is uniformly dispersed on degradable polymeric matrices through solution casting or non-solvent precipitation to make the composite material reach nanometer composition, so that the performance of the composite material is improved. The nanometer structured degradable biomedical composite material of the present invention can be widely used in the fields of bone screws, bone knitting boards, bone tissue engineering and other biological medical material.
Description
Technical field
The present invention relates to a kind of degradable biomedicine composite material in nanometer structure and preparation method thereof, belong to the technical field of bio-medical substitution material preparation.
Background technology
Owing to reasons such as disease or wounds, sclerous tissueses such as people's skeleton or tooth produce sclerous tissues's damage or disappearance, need a large amount of synthetic substitution material to repair and treat.Hard tissue substituting material mainly contains metal, pottery and polymer three class materials at present.They respectively have characteristics.
Strength of Metallic Materials height, processing easily.But cost an arm and a leg, do not match with bone stress, can produce osseous tissue and absorb, the metal ion that the physiology corrosion produces produces untoward reaction to tissue, and this class material require second operation takes out after the organization healing.
Calcium phosphate material because of its have with skeleton in inorganic mutually similar chemical composition, good biological activity and bone conductibility, be the ceramic material of using widely.But its relatively poor mechanical property has limited the range of application of calcium phosphate, is mainly used in nonweight-bearing field (as the filling of bone lacks and bone cement etc.).
Polymeric material mainly contains two kinds: biological non-degradable material and Biodegradable material.The former is as polyethylene, polypropylene, politef and polymethyl methacrylate etc.These materials have mechanical property and bio-compatible preferably, but they do not possess biological activity, and cannot degrade, and need second operation to take out.The latter such as α-polyester polymer have good mechanical performance and biocompatibility, and its maximum characteristics are can degrade behind the implant into body, along with the healing of tissue, implant is slowly degraded, after the organization healing, the implant degraded is complete, thereby does not want second operation.But this class degradation material also exists many deficiencies: X ray did not develop after material implanted, and can't effectively detect the implantation situation; This class material is along with the increase of degradation time, and mechanical properties decrease is too fast; The acidic materials that produce in degradation process can cause tissue to produce the aseptic inflammation reaction.
The biodegradation rate of calcium phosphate material can be regulated.The degradation rate of the calcium phosphate of Different Ca/P ratio and degree of crystallinity is different, and their descending orders are: α-TCP＞β-TCP＞HA, the calcium phosphate of the calcium phosphate＞high-crystallinity of amorphous calcium phosphate＞low-crystallinity.If the calcium phosphate of different crystalline phases is together compound, promptly can regulate the degradation rate of calcium phosphate.
Therefore, people join the degradable polymer preparation organic/inorganic composite material similar to bone structure from the structure angle of osseous tissue with calcium phosphate.Calcium phosphate is filled into polymer manufacture degradable biomedical Biocomposite material has the incomparable advantage of single constituent: (1) can improve the deficiency of the mechanical property of calcium phosphate own aspect the mechanical property, has improved the toughness of material; (2) aspect biological activity, add biological that not commensurability calcium phosphate can reinforced polymeric material; (3) aspect biodegradation, the acidic materials that add calcium phosphate post polymerization deposits yields can be suppressed effectively, the crystalline phase by regulating calcium phosphate and crystalline phase is formed or the proportion of composing of the monomer of polymer and each monomeric proportion of composing of copolymer or calcium phosphate and polymer can be regulated the biodegradation rate of composite; (3) in the medical science context of detection, behind the interpolation calcium phosphate, implant can develop by X ray, detects the implantation situation and is more prone to; In addition, the acidic materials that polymer produces can promote the degraded of calcium phosphate, help the healing of osseous tissue more.
Chinese patent (CN1403167) and United States Patent (USP) (US5981619) disclose calcium phosphate added and have obtained mechanical property composite preferably in the polymer.But these composite structures are compared with the structure of osseous tissue, also exist difference: the particle size that mainly is calcium phosphate is bigger, and (calcium phosphate in the skeleton is tens nm, and their calcium phosphate is 1～100 μ m), the degradation property of composite is good inadequately, goes back organic/inorganic substance and disperses even inadequately at polymeric matrix.Foregoing invention can not be regulated composite degradation speed effectively, to satisfy the requirement of different implant sites to the implant degradation rate.In addition, the appearance of bone tissue engineer and development need also to have proposed the adjustable requirement of biodegradation rate to porous support materials.
Summary of the invention
The object of the present invention is to provide tiny and each granule of a kind of calcium phosphate granules all have compoundization of two-phase structure, and can be in polymeric matrix finely dispersed degradable biomedicine composite material in nanometer structure and preparation method thereof.
Degradable biomedicine composite material in nanometer structure of the present invention is that 5～50% nano-structured calcium phosphate and mass percentage content are that 95～50% degradable polymer is formed by mass percentage content, wherein, nano-structured calcium phosphate is that size is the multiple phase calcium phosphate calcium granule of 40nm～500nm, each multiple phase calcium phosphate calcium granule is compound or apatite/β phase tricalcium phosphate is compound or the compound crystal grain of α phase tricalcium phosphate/compound two-phase of β phase tricalcium phosphate constitutes by apatite/α phase tricalcium phosphate, and crystallite dimension is 5nm-40nm.
Degradable biomedicine composite material in nanometer structure of the present invention can be film like complex or Powdered complex or supply other form bio-medical succedaneum of preparation, as the composite of bone screw or bone fishplate bar.
The preparation method of the degradable biomedicine composite material in nanometer structure of invention has following two kinds of schemes:
Scheme 1
Preparation method may further comprise the steps:
1) with ultrasound wave or machinery emulsification machine nano-structured calcium phosphate granules is dispersed in the organic solvent, the mass/volume degree of nano-structured calcium phosphate in organic solvent is 0.1%～10%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, forms homogeneous mixture solotion, the mass/volume percent concentration of polymer solution is 1%～10%;
3) homogeneous mixture solotion is made the film like complex with the solution casting method casting, or adopt the non-solvent sedimentation method to make Powdered complex, carry out drying again.
Further preparation, can adopt composite hot-forming or that injection mo(u)lding is made confession preparation bio-medical succedaneum with the film like complex or the Powdered complex of gained, its hot-forming step is as follows: above-mentioned laminated film or composite powder are put in the mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5MPa～40MPa, be that 80～190 ℃, pressure are under the condition of 0.5～100MPa in temperature then, pressurize 5～30 minutes, goods are taken out in cooling;
The injection mo(u)lding step is as follows: with above-mentioned film like complex or Powdered complex pulverize at low temperature, add hot injection mo(u)lding in the injection machine to, condition of molding is: injection pressure is 0.1MPa～5Mpa, and temperature is 100 ℃～250 ℃.
The bending strength of the degradable biomedicine composite material in nanometer structure of the densification that scheme 1 makes is 80～250MPa, and bending modulus is 1～10Gpa.
Scheme 2
Preparation method may further comprise the steps:
1) under the effect of ultrasound wave or machinery emulsification machine, nano-structured calcium phosphate granules and pore creating material are joined in the organic solvent, the mass/volume degree of nano-structured calcium phosphate in organic solvent is 0.1%～10%, and the mass/volume degree of pore creating material in organic solvent is 1%～20%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, forms homogeneous mixture solotion, the mass/volume percent concentration of polymer solution is 1%～10%;
3) homogeneous mixture solotion is made the film like complex with the solution casting method casting, or adopt the non-solvent sedimentation method to make Powdered complex, carry out drying again.
Further preparation, the film like complex that contains pore creating material or the Powdered complex of gained can be put in the mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5～40MPa, be that 80～190 ℃, pressure are under the condition of 0.5～100MPa in temperature then, pressurize 5～30 minutes, goods are taken out in cooling, it is immersed in 37 ℃ the thermostatic water bath, and stripping pore creating material under the frequency of oscillation of 10～100 times/h obtains composite porous.
The injection mo(u)lding step is as follows: with above-mentioned film like complex or Powdered complex pulverize at low temperature, add hot injection mo(u)lding in the injection machine to, condition of molding is: injection pressure is 0.1MPa～5Mpa, and temperature is 100 ℃～250 ℃.The bending strength of the degradable biomedicine composite material in nanometer structure of the densification that this scheme makes is 80～250MPa, and bending modulus is 1～10Gpa.
The aperture of the porous degradable biomedicine composite material in nanometer structure that scheme 2 makes is 10 μ m～200 μ m, and porosity is 75%～95%, and compressive strength is 0.5MPa～3MPa.
Among the present invention, described nano-structured calcium phosphate composite powder comprises: apatite/α phase tricalcium phosphate composite powder or apatite/β phase tricalcium phosphate composite powder or α phase tricalcium phosphate/β phase tricalcium phosphate composite particles, wherein apatite is fluoridated hydroxyapatite or contains carbonate apatite.Crystallite dimension in the granule is about 5nm～40nm.The content of each phase in the nano-structured calcium phosphate multiphase granules is 0～100% scalable, and crystalline phase that the degradation rate of calcium phosphate can be by changing calcium phosphate or crystalline phase are formed and regulated.
Among the present invention, described degradable polymer comprises: polylactic acid or polyglycolic acid or poly butyric or poly-own lactone or poly-to dioxanone or poly-anhydride or poly-former ester or their monomeric copolymers, wherein polylactic acid is poly--L-lactic acid or poly--(D, L)-and lactic acid or poly--L-(D, L)-lactic acid.The degradation rate of polymer can be regulated by the monomer composition and the ratio that change in the polymer.
In the preparation process of the present invention, described organic solvent can be dichloromethane or chloroform or oxolane or dimethyl formamide or dimethyl sulfoxide or dioxane.Pore creating material can be with sodium chloride or sugar.Used reagent is methanol or ethanol when adopting the non-solvent sedimentation method.
The preparation process condition that the present invention adopts is simple, simple to operate, and cost is low, is easy to industrialization.This preparation method adopts solvent solution-cast or solution-non-solvent precipitation that nano-structured calcium phosphate powder is dispersed in the degradable polyalcohol group body by selecting organic solvent, thereby it is compound to make composite reach nanoscale, brings into play the usefulness of composite more fully.In addition, can obtain porous nanometer structure degradable biological medical composite by particle filtering method.Degradable biomedicine composite material in nanometer structure of the present invention, its biodegradation rate can be by changing nano-structured calcium phosphate composition and kind or the composition of polymer or the proportion of composing of calcium phosphate and polymer regulated effectively, special needs to be pointed out is, nano-structured among the present invention, the two-phase complex calcium phosphate has unique, be different from the Synergistic degradation behavior of arbitrary single-phase calcium phosphate in its component, its degradation rate is greater than arbitrary single-phase calcium phosphate in its component, and this can make this material in the requirement of satisfying the different tissues engineering to a greater extent.The acidic materials that this material polymers produces can promote the degraded of calcium phosphate, help the healing of osseous tissue more.The mechanical property of its mechanical property and bone is complementary.Can be widely used for biomedical materials field such as bone screw, bone fishplate bar and bone tissue engineer.
The specific embodiment
Degradable biomedicine composite material in nanometer structure of the present invention is made up of nano-structured calcium phosphate and degradable polymer, wherein the mass percentage content of nano-structured calcium phosphate is 5～50%, and the mass percentage content of degradable polymer is 95～50%.
When preparing fine and close degradable biomedicine composite material in nanometer structure, earlier calcium phosphate is joined in the organic solvent, under ultrasound wave or the effect of machinery emulsification machine, form uniform calcium phosphate solution, under 10 ℃～60 ℃, polymer is joined in the calcium phosphate solution again, treat under the magnetic agitation that polymer dissolves back ultrasound wave or the effect of machinery emulsification machine 10～30 minutes fully, be cast into calcium phosphate/degradable polymer film like complex again or add a large amount of ethanol or methanol extraction goes out the Powdered complex of calcium phosphate/degradable polymer.Again that Powdered complex or film like complex is following dry 24 hours at 40～60 ℃, again 40～60 ℃ of following vacuum dryings 48 hours,, take out Powdered complex of calcium phosphate/degradable polymer or film like complex and put into exsiccator 5 ℃ of cold preservations are standby to constant weight up to dry thing.
The Powdered complex of calcium phosphate/degradable polymer or the thermoforming of film like complex has dual mode: hot compression molding and hot injection mo(u)lding.Hot compression molding route: above-mentioned Powdered complex or film like complex are put in the special mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5MPa～40MPa, be that 80～190 ℃, pressure are under the condition of 0.5～100MPa in temperature then, pressurize 5～30 minutes, goods are taken out in cooling, are processed into the samples such as bone screw, bone fishplate bar of required form then on lathe.It is standby to seal cold preservation after sample process oxireme or the gamma-radiation sterilization up for safekeeping.
Hot injection mo(u)lding route:, add hot injection mo(u)lding in the injection machine to above-mentioned Powdered complex or film like complex pulverize at low temperature.Condition of molding is: injection pressure is that 0.1MPa～5MPa temperature is 100 ℃～250 ℃.Injection mold is bone screw bone fishplate bar mould of required special shape etc.Can obtain required bone screw, bone fishplate bar etc. after sample process pruning that injection mo(u)lding obtains and oxireme or the gamma-radiation sterilization, it is standby that sample is sealed cold preservation up for safekeeping.
Prepare porous degradable biomedicine composite material in nanometer structure, earlier nano-structured calcium phosphate and pore creating material (sodium chloride or sugar) are joined and under the ultrasound wave or the situation of machinery emulsification machine effect, form uniform solution in the organic solvent, polymer is joined in the calcium phosphate solution again, magnetic agitation treats that polymer dissolves back ultrasound wave or the effect of machinery emulsification machine 10～30 minutes fully, is cast into the film like complex again or adds a large amount of ethanol or methanol extraction goes out the Powdered complex of calcium phosphate/degradable polymer.Again with Powdered complex or film like complex 40～60 ℃ dry 24 hours down, again 40～60 ℃ of following vacuum dryings 48 hours, to constant weight, taking out calcium phosphate/degradable polymer thin film or powder, to put into 5 ℃ of cold preservations of exsiccator standby up to dry thing.
Above-mentioned Powdered complex or film like complex are put in the special mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5～40MPa, be that 80～190 ℃, pressure are under the condition of 0.5～100MPa in temperature then, pressurize 5～30 minutes, goods are taken out in cooling, be immersed in then in 37 ℃ the thermostatic water bath, stripping pore creating material under the frequency of oscillation of 100 times/h, soak time is 72 hours, per hour changed one time water in preceding 12 hours, changed water one time, changed once in later per 8 hours in back 36 hours 6 hours.The aperture that obtains behind the filtering pore creating material is nano-structured calcium phosphate/degradable pollutant polyalcohol stephanoporate composite of 10 μ m～200 μ m.
Further specify the present invention below in conjunction with embodiment
Embodiment 1
Nano-structured apatite/β phase tricalcium phosphate composite powder of 1g is added in the oxolane of 400ml, after the supersonic oscillations 15 minutes, add the 7.2g polylactic acid, become film like casting in after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving in the mould that diameter is 38mm, after under 40 ℃ dry 24 hours, putting in the vacuum drying oven vacuum drying till the constant mass of thin film, is that calcium phosphate/lactic acid composite material of 12.2wt% is put into exsiccator cold preservation with the apatite/β phase tricalcium phosphate composite powder content that obtains.
Embodiment 2
Nano-structured apatite/α phase tricalcium phosphate composite powder of 2g is added in the dimethyl formamide of 1500ml, after the supersonic oscillations 15 minutes, add the poly-own lactone of 38g, become film like casting in after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving in the mould that diameter is 38mm, after under 160 ℃ dry 24 hours, putting in the vacuum drying oven vacuum drying till the constant mass of thin film, with the α phase tricalcium phosphate content that obtains be the calcium phosphate/poly-of 5wt% in oneself resin composite material put into exsiccator cold preservation.
Embodiment 3
Nano-structured α phase tricalcium phosphate/β phase tricalcium phosphate composite powder of 1g is added in the dimethyl sulfoxide of 300ml, after the supersonic oscillations 15 minutes, add the 4g polylactic acid, become film like casting in after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving in the mould that diameter is 38mm, after under 160 ℃ dry 24 hours, putting in the vacuum drying oven vacuum drying till the constant mass of thin film, is that calcium phosphate/lactic acid composite material of 20wt% is put into exsiccator cold preservation with the α phase tricalcium phosphate composite powder/β phase tricalcium phosphate composite powder content that obtains.
Embodiment 4
The 10g sugar that nano-structured apatite/α phase tricalcium phosphate composite powder and the granularity of 1.5g is 200～300 μ m adds in the oxolane of 200ml, after the supersonic oscillations 15 minutes, add the 6.0g polylactic acid, become film like casting in after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving in the mould that diameter is 38mm, after under 40 ℃ dry 24 hours, vacuum drying is calcium phosphate/sugar/lactic acid composite material of 20wt% with the calcium phosphate content that obtains till the constant mass of thin film in the vacuum drying oven putting into.At room temperature with the pressure precompressed of 30MPa, is 180 ℃, pressure be the condition of 40MPa under in temperature then with above-mentioned composite, and pressurize 5 minutes, is taken out goods at cooling.Goods are put into 37 ℃ thermostatic water bath and are soaked under the frequency of oscillation of 100 times/h, and soak time is 72 hours, per hour changes water one time, changes water one time, changed once in later per 8 hours in back 36 hours 6 hours in preceding 12 hours.Obtain the aperture after the filtering sugar and be about 200 μ m, porosity is 90%, compressive strength is at porous, degradable calcium phosphate/degradable polymer composite material of 2MPa.
Embodiment 5
Composite with embodiment 1 acquisition, put in the special mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 30MPa, be that 180 ℃, pressure are under the condition of 40MPa in temperature then, pressurize 5 minutes, is taken out goods at cooling, is processed into the samples such as bone screw, bone fishplate bar of required form then on lathe.It is standby to seal cold preservation after sample process oxireme or the gamma-radiation sterilization up for safekeeping.
Embodiment 6
With the composite that embodiment 1 obtains, pulverize at low temperature is added hot injection mo(u)lding in the injection machine to.Condition of molding such as table 1.Injection mold is the bone screw bone fishplate bar mould of required special shape.Can obtain required bone screw, bone fishplate bar etc. after sample process pruning that injection mo(u)lding obtains and oxireme or the gamma-radiation sterilization, it is standby that sample is sealed cold preservation up for safekeeping.
The injection molding process condition of table 1 calcium phosphate poly lactic acid nano composite material
| Labor and materials district temperature | First section thermal treatment zone | Second section thermal treatment zone | The 3rd section thermal treatment zone | The discharging opening temperature | Injection pressure | Mold temperature |
| 45℃ | 200℃ | 215℃ | 220℃ | 200℃ | 0.15MPa | Room temperature |
Claims (10)
1. a densification or porous degradable biomedicine composite material in nanometer structure, it is characterized in that by mass percentage content being that 5～50% nano-structured calcium phosphate and mass percentage content are that 95～50% degradable polymer is formed, wherein, nano-structured calcium phosphate is that size is the multiple phase calcium phosphate calcium granule of 40nm～500nm, each multiple phase calcium phosphate calcium granule is compound or apatite/β phase tricalcium phosphate is compound or the compound crystal grain of α phase tricalcium phosphate/compound two-phase of β phase tricalcium phosphate constitutes by apatite/α phase tricalcium phosphate, and crystallite dimension is 5nm-40nm.
2. according to the described degradable biomedicine composite material in nanometer structure of claim 1, it is characterized in that described apatite is fluoridated hydroxyapatite or contains carbonate apatite.
3. according to the described degradable biomedicine composite material in nanometer structure of claim 1, it is characterized in that described degradable polymer is polylactic acid, polyglycolic acid, poly butyric, poly-own lactone, poly-any or their monomeric copolymers in dioxanone, poly-anhydride or the poly-former ester, wherein polylactic acid is poly--L-lactic acid or poly--(D, L)-and lactic acid or poly--L-(D, L)-lactic acid.
4. according to the described degradable biomedicine composite material in nanometer structure of claim 1, it is characterized in that said composite is film like complex or Powdered complex or the composite that supplies other form bio-medical succedaneum of preparation, said bio-medical succedaneum is bone screw or bone fishplate bar.
5. according to the preparation method of the degradable biomedicine composite material in nanometer structure of the described densification of claim 1, it is characterized in that may further comprise the steps:
1) with ultrasound wave or machinery emulsification machine nano-structured calcium phosphate granules is dispersed in the organic solvent, the mass/volume degree of nano-structured calcium phosphate granules in organic solvent is 0.1%～10%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, forms homogeneous mixture solotion, the mass/volume percent concentration of polymer solution is 1%～10%;
3) homogeneous mixture solotion is made the film like complex with the solution casting method casting, or adopt the non-solvent sedimentation method to make Powdered complex, carry out drying again.
6. according to the described preparation method of claim 5, it is characterized in that organic solvent is dichloromethane or chloroform or oxolane or dimethyl formamide or dimethyl sulfoxide or dioxane.
7. according to the preparation method of the degradable biomedicine composite material in nanometer structure of the described densification of claim 5, it is characterized in that also comprising and adopt hot-forming or injection mo(u)lding to make composite the film like complex of gained or Powdered complex for preparation bio-medical succedaneum, its hot-forming step is as follows: above-mentioned film like complex or Powdered complex are put in the mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5MPa～40MPa, it is 80～190 ℃ in temperature then, pressure is under the condition of 0.5～100MPa, pressurize 5～30 minutes, goods are taken out in cooling;
The injection mo(u)lding step is as follows: with above-mentioned film like complex or Powdered complex pulverize at low temperature, add hot injection mo(u)lding in the injection machine to, condition of molding is: injection pressure is 0.1MPa～5Mpa, and temperature is 100 ℃～250 ℃.
8. according to the preparation method of the described porous degradable biomedicine composite material in nanometer structure of claim 1, it is characterized in that may further comprise the steps:
1) under the effect of ultrasound wave or machinery emulsification machine, nano-structured calcium phosphate granules and pore creating material are joined in the organic solvent, the mass/volume degree of nano-structured calcium phosphate granules in organic solvent is 0.1%～10%, and the mass/volume degree of pore creating material in organic solvent is 1%～20%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, forms homogeneous mixture solotion, the mass/volume percent concentration of polymer solution is 1%～10%;
3) homogeneous mixture solotion is made the film like complex with the solution casting method casting, or adopt the non-solvent sedimentation method to make Powdered complex, carry out drying again.
9. according to the described preparation method of claim 8, it is characterized in that organic solvent is dichloromethane or chloroform or oxolane or dimethyl formamide or dimethyl sulfoxide or dioxane.
10. according to the preparation method of the described porous degradable biomedicine composite material in nanometer structure of claim 8, it is characterized in that also comprising that film like complex or Powdered complex with gained adopt the hot-forming composite of making for preparation bio-medical succedaneum, hot-forming step is as follows: above-mentioned laminated film or composite powder are put in the mould, amount of filling is 70% of a mould, earlier at room temperature with the pressure precompressed of 0.5～40MPa, it is 80～190 ℃ in temperature then, pressure is under the condition of 0.5～100MPa, pressurize 5～30 minutes, goods are taken out in cooling, it is immersed in 37 ℃ the thermostatic water bath, stripping pore creating material under the frequency of oscillation of 10～100 times/h obtains composite porous.
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| CN104146783A (en) * | 2014-08-27 | 2014-11-19 | 吉林大学 | Degradable micro-implant anchorage device |
| CN104606279B (en) * | 2014-12-31 | 2019-05-24 | 广东国源国药制药有限公司 | Porous nano biological multi-calcium and application thereof |
| CN108421088B (en) * | 2018-04-19 | 2021-06-11 | 奥精医疗科技股份有限公司 | Mineralized collagen-based medium-strength artificial bone repair material and preparation method thereof |
| CN111300841A (en) * | 2020-03-02 | 2020-06-19 | 华东理工大学 | High-strength absorbable composite active internal fixation device and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1488574A (en) * | 2003-07-28 | 2004-04-14 | 浙江大学 | Method for preparing biomedical amorphous nano calcium phosphate |
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| CN1485098A (en) * | 2003-08-08 | 2004-03-31 | 浙江大学 | Degradable nanometer composite material for biological and medical use |
Non-Patent Citations (3)
| Title |
|---|
| 有机-羟基磷灰石复合骨替代材料 沈序辉等，材料科学与工程，第17卷第4期 1999 * |
| 高聚物骨替代材料复合技术的研究进展 章蓉等，材料导报，第17卷第8期 2003 * |
| 高聚物骨替代材料复合技术的研究进展 章蓉等，材料导报，第17卷第8期 2003;有机-羟基磷灰石复合骨替代材料 沈序辉等，材料科学与工程，第17卷第4期 1999 * |
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