CN1270783C - Degradable nanometer composite material for biological and medical use - Google Patents
Degradable nanometer composite material for biological and medical use Download PDFInfo
- Publication number
- CN1270783C CN1270783C CN 03142161 CN03142161A CN1270783C CN 1270783 C CN1270783 C CN 1270783C CN 03142161 CN03142161 CN 03142161 CN 03142161 A CN03142161 A CN 03142161A CN 1270783 C CN1270783 C CN 1270783C
- Authority
- CN
- China
- Prior art keywords
- calcium phosphate
- composite material
- poly
- composite powder
- preparation
- 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
- 239000002131 composite material Substances 0.000 title claims abstract description 70
- 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 108
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 106
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 77
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 77
- 239000000843 powder Substances 0.000 claims abstract description 49
- 235000019731 tricalcium phosphate Nutrition 0.000 claims abstract description 29
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims abstract description 29
- 229940078499 tricalcium phosphate Drugs 0.000 claims abstract description 29
- 229920006237 degradable polymer Polymers 0.000 claims abstract description 28
- 229910052586 apatite Inorganic materials 0.000 claims abstract description 19
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 claims abstract description 19
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000011575 calcium Substances 0.000 claims abstract description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- 239000000463 material Substances 0.000 claims description 54
- 238000002360 preparation method Methods 0.000 claims description 28
- 238000002347 injection Methods 0.000 claims description 22
- 239000007924 injection Substances 0.000 claims description 22
- 239000002114 nanocomposite Substances 0.000 claims description 22
- 229920000642 polymer Polymers 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 10
- 238000004945 emulsification Methods 0.000 claims description 10
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 10
- 239000004626 polylactic acid Substances 0.000 claims description 10
- 238000002604 ultrasonography Methods 0.000 claims description 10
- 238000005266 casting Methods 0.000 claims description 9
- 239000004310 lactic acid Substances 0.000 claims description 9
- 239000011148 porous material Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000011049 filling Methods 0.000 claims description 8
- 239000008240 homogeneous mixture Substances 0.000 claims description 8
- 230000010355 oscillation Effects 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 150000002596 lactones Chemical class 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 238000000465 moulding Methods 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-UHFFFAOYSA-N 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 3
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 3
- 239000004633 polyglycolic acid Substances 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 abstract description 29
- 238000006731 degradation reaction Methods 0.000 abstract description 12
- 230000015556 catabolic process Effects 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 5
- 238000001914 filtration Methods 0.000 abstract description 4
- 239000002245 particle Substances 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract 2
- 239000003519 biomedical and dental material Substances 0.000 abstract 1
- 238000009940 knitting Methods 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 239000010408 film Substances 0.000 description 15
- 239000010409 thin film Substances 0.000 description 11
- 238000001291 vacuum drying Methods 0.000 description 10
- 238000004321 preservation Methods 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000007943 implant Substances 0.000 description 6
- 238000006065 biodegradation reaction Methods 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000009210 therapy by ultrasound Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000007669 thermal treatment Methods 0.000 description 3
- 238000013019 agitation Methods 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000748 compression moulding Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000002481 ethanol extraction Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000003808 methanol extraction Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- -1 polyethylene Polymers 0.000 description 2
- 238000013138 pruning Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011173 biocomposite Substances 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 229910010293 ceramic material Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000805 composite resin Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 229910003471 inorganic composite material Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229950000845 politef Drugs 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000003856 thermoforming Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The present invention discloses a degradable biomedical nanometer composite material and a preparing method thereof. The speed rate of biological degradation of the composite material is adjusted through different Ca/P ratios in an inorganic phase, different crystalline states and different composite ratios of the inorganic phase, and the composite material is compounded with degradable polymers, so that the speed rate of biological degradation of the whole composite material can be adjusted. The inorganic phase is composed of one or two of amorphous calcium phosphate, alpha phase tricalcium phosphate, beta phase tricalcium phosphate, apatite and calcium hydrophosphate. Organic solvent is selected in the preparing method to make calcium phosphate powder uniformly dispersed in degradable polymeric matrices through solvent dissolution, pouring or dissolution and non solvent precipitation, so that the composite material reaches nanometer composition, and the efficacy of the composite material can be performed sufficiently. In addition, a particle filtering method can be adopted to obtain porous nanometer composite material. The nanometer composite material of the present invention can be widely used in biomedical material fields of bone screws, bone knitting boards, bone tissue engineering, etc.
Description
Technical field
The present invention relates to a kind of degradable biological medical nano composite material 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 a kind of calcium phosphate granules tiny, in polymeric matrix finely dispersed degradable biological medical nano composite material and preparation method thereof.
Laminated film that degradable biological medical nano composite material of the present invention is made up of calcium phosphate and degradable polymer or composite powder or for the composite of preparation bio-medical succedaneum, wherein the content of calcium phosphate (mass percent) is 5～50%, and the content of degradable polymer (mass percent) is 95～50%.
The preparation method of degradable biological medical nano composite material of the present invention has:
Scheme 1
Preparation method may further comprise the steps:
1) under the effect of ultrasound wave or machinery emulsification machine calcium phosphate is dispersed in the organic solvent, the content (by mass/volume percentage ratio) of calcium phosphate in organic solvent is 0.1%～10%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, through the effect formation homogeneous mixture solotion of ultrasound wave or machinery emulsification machine, the mass/volume percent concentration of polymer solution is 1%～10%.
3) adopt conventional solution casting method to be cast into calcium phosphate/degradable polymer laminated film homogeneous mixture solotion, or adopt conventional non-solvent intermediate processing to be settled out calcium phosphate/degradable polymer composite powder, 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 laminated film or the composite powder 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 composite powder or laminated film 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 biological medical nano composite material 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 calcium phosphate and pore creating material are joined in the organic solvent, the content (by mass/volume percentage ratio) of calcium phosphate in organic solvent is 0.1%～10%;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in the above-mentioned mixed solution, through the effect formation homogeneous mixture solotion of ultrasound wave or machinery emulsification machine, the mass/volume percent concentration of polymer solution is 1%～10%.
3) homogeneous mixture solotion is adopted conventional solution casting method be cast into calcium phosphate/degradable polymer laminated film, or adopt conventional non-solvent intermediate processing to be settled out calcium phosphate/degradable polymer composite powder, to carry out drying again.
Further preparation, can adopt hot-forming laminated film or composite powder to make for the composite for preparing the bio-medical succedaneum with gained, 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 100 times/h obtains composite porous.
The aperture of the degradable biological medical nano composite material 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 calcium phosphate comprises: amorphous calcium phosphate or α phase tricalcium phosphate or β phase tricalcium phosphate or apatite or calcium hydrogen phosphate or apatite/α phase tricalcium phosphate composite powder or apatite/β phase tricalcium phosphate composite powder or α phase tricalcium phosphate composite powder/β phase tricalcium phosphate composite powder, wherein apatite is fluoridated hydroxyapatite or contains carbonate apatite.These particles of powder are evenly distributed, size is generally about 40nm～500nm, wherein the content of each phase in the calcium phosphate composite powder is 0～100% scalable, and crystalline phase that the degradation rate of (promptly regulate Ca/P than) 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.Non-solvent is methanol or ethanol.
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 to precipitate in the calcium phosphate powder homodisperse 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 the porous nano composite by particle filtering method.Biological medical nano composite of the present invention, its biodegradation rate can be by changing calcium phosphate composition or the composition of polymer or the proportion of composing of calcium phosphate and polymer regulated effectively, thereby can satisfy the requirement of different tissues engineering.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 biological medical nano composite material of the present invention is made up of calcium phosphate and degradable polymer, and wherein the content of calcium phosphate (mass percent) is 5～50%, and the content of degradable polymer (mass percent) is 95～50%.
During employing scheme 1 preparation degradable biological medical nano composite material, earlier calcium phosphate is joined and under ultrasound wave or the effect of machinery emulsification machine, form uniform calcium phosphate aaerosol solution in the organic solvent, under 10 ℃～60 ℃, polymer is joined in the calcium phosphate aaerosol 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 thin film again or add a large amount of ethanol or methanol extraction goes out calcium phosphate/degradable polymer composite powder.Again with powder or thin film 40～60 ℃ dry 24 hours down, again 40～60 ℃ of following vacuum dryings 48 hours, till the quality of dry thing no longer reduced, taking out calcium phosphate/degradable polymer thin film or powder, to put into 5 ℃ of cold preservations of exsiccator standby.
Calcium phosphate/degradable polymer thin film or powder thermoforming have dual mode: hot compression molding and hot injection mo(u)lding.Hot compression molding route: above-mentioned laminated film or composite powder 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 composite powder or laminated film 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.
Employing scheme 2 can prepare porous, degradable biological medical nano composite, earlier 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 aaerosol solution in the organic solvent, polymer is joined in the calcium phosphate aaerosol solution again, magnetic agitation treats that polymer dissolves back ultrasound wave or the effect of machinery emulsification machine 10～30 minutes fully, again casting film or add a large amount of ethanol or methanol extraction goes out calcium phosphate/degradable polymer composite powder.Again with powder or thin film 40～60 ℃ dry 24 hours down, again 40～60 ℃ of following vacuum dryings 48 hours, till the quality of dry thing was not reducing, taking out calcium phosphate/degradable polymer thin film or powder, to put into 5 ℃ of cold preservations of exsiccator standby.
Above-mentioned thin film or powder 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 calcium phosphate/degradable pollutant polyalcohol stephanoporate nano composite material of 10 μ m～200 μ m.
Further specify the present invention below in conjunction with embodiment
Embodiment 1
Apatite/β phase tricalcium phosphate composite powder of 0.4g is added in the oxolane of 200ml, after the supersonic oscillations 15 minutes, add the 3.6g polylactic acid, casting in film forming in the mould that diameter is 38mm after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving, 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 10wt% is put into exsiccator cold preservation with the apatite/β phase tricalcium phosphate composite powder content that obtains.
Embodiment 2
The α phase tricalcium phosphate powder of 0.2g is added in the dimethyl formamide of 200ml, after the supersonic oscillations 15 minutes, add the poly-own lactone of 3.8g, casting in film forming in the mould that diameter is 38mm after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving, 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
α phase tricalcium phosphate composite powder/β phase tricalcium phosphate composite powder of 0.8g is added in the dimethyl sulfoxide of 200ml, after the supersonic oscillations 15 minutes, add the 3.2g polylactic acid, casting in film forming in the mould that diameter is 38mm after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving, 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 sodium chloride that apatite/α phase tricalcium phosphate composite powder and the granularity of 0.8g is 200～300 μ m adds in the oxolane of 200ml, after the supersonic oscillations 15 minutes, add the 3.2g polylactic acid, casting in film forming in the mould that diameter is 38mm after the ultrasonic Treatment after 50 ℃ of lower magnetic force stirring and dissolving, after under 40 ℃ dry 24 hours, vacuum drying is calcium phosphate/sodium chloride/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.The aperture that obtains behind the filtering sodium chloride is 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. the preparation method of degradable biological medical nano composite material is characterized in that may further comprise the steps:
1) under the effect of ultrasound wave or machinery emulsification machine calcium phosphate is dispersed in the organic solvent, the content of calcium phosphate in organic solvent is 0.1%～10% by mass/volume percentage ratio;
2) under 10 ℃～60 ℃ degradable polymer is dissolved in calcium phosphate-organic solvent mixed solution, through the effect formation homogeneous mixture solotion of ultrasound wave or machinery emulsification machine, the mass/volume percent concentration of polymer solution is 1%～10%;
3) adopt conventional solution casting method to be cast into calcium phosphate/degradable polymer laminated film homogeneous mixture solotion, or adopt conventional non-solvent intermediate processing to be settled out calcium phosphate/degradable polymer composite powder, carry out drying again.
2. according to the described preparation method of claim 1, it is characterized in that organic solvent is dichloromethane or chloroform or oxolane or dimethyl formamide or dimethyl sulfoxide or dioxane.
3. according to the preparation method of the described degradable biological medical nano composite material of claim 1, it is characterized in that also comprising and adopt hot-forming or injection mo(u)lding to make composite the laminated film of gained or composite powder for preparation bio-medical succedaneum, 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, 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 composite powder or laminated film 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 ℃.
4. according to the preparation method of the described degradable biological medical nano composite material of claim 1, it is characterized in that described calcium phosphate is amorphous calcium phosphate or α phase tricalcium phosphate or β phase tricalcium phosphate or apatite or calcium hydrogen phosphate or apatite/α phase tricalcium phosphate composite powder or apatite/β phase tricalcium phosphate composite powder or α phase tricalcium phosphate composite powder/β phase tricalcium phosphate composite powder, wherein apatite is fluoridated hydroxyapatite or contains carbonate apatite.
5. according to the preparation method of the described degradable biological medical nano composite material of claim 1, it is characterized in that described degradable polymer is 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.
6. the preparation method of degradable biological medical nano composite material is characterized in that may further comprise the steps:
1) calcium phosphate and pore creating material are joined in the organic solvent, the content of calcium phosphate in organic solvent is 0.1%～10% by mass/volume percentage ratio;
2) degradable polymer is dissolved in the above-mentioned mixed solution forms homogeneous mixture solotion, the mass/volume percent concentration of polymer solution is 1%～10%;
3) homogeneous mixture solotion is adopted conventional solution casting method be cast into calcium phosphate/degradable polymer laminated film, or adopt conventional non-solvent intermediate processing to be settled out calcium phosphate/degradable polymer composite powder, to carry out drying again.
7. according to the described preparation method of claim 6, it is characterized in that organic solvent is chloroform or oxolane or dimethyl formamide or dimethyl sulfoxide or dioxane; Pore creating material is sodium chloride or sugar.
8. according to the preparation method of the described degradable biological medical nano composite material of claim 6, it is characterized in that also comprising that laminated film or composite powder 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 100 times/h obtains composite porous.
9. according to the preparation method of the described degradable biological medical nano composite material of claim 6, it is characterized in that described calcium phosphate is amorphous calcium phosphate or α phase tricalcium phosphate or β phase tricalcium phosphate or apatite or calcium hydrogen phosphate or apatite/α phase tricalcium phosphate composite powder or apatite/β phase tricalcium phosphate composite powder or α phase tricalcium phosphate composite powder/β phase tricalcium phosphate composite powder, wherein apatite is fluoridated hydroxyapatite or contains carbonate apatite.
10. according to the preparation method of the described degradable biological medical nano composite material of claim 6, it is characterized in that described degradable polymer is 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03142161 CN1270783C (en) | 2003-08-08 | 2003-08-08 | Degradable nanometer composite material for biological and medical use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03142161 CN1270783C (en) | 2003-08-08 | 2003-08-08 | Degradable nanometer composite material for biological and medical use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1485098A CN1485098A (en) | 2004-03-31 |
| CN1270783C true CN1270783C (en) | 2006-08-23 |
Family
ID=34155628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03142161 Expired - Fee Related CN1270783C (en) | 2003-08-08 | 2003-08-08 | Degradable nanometer composite material for biological and medical use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1270783C (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1314462C (en) * | 2005-04-25 | 2007-05-09 | 浙江大学 | Degradable biomedicine composite material in nanometer structure and its prepn process |
| CN100356991C (en) * | 2005-09-28 | 2007-12-26 | 浙江大学 | Biological medical material with biological responding coating and preparing method |
| CN100428963C (en) * | 2005-11-30 | 2008-10-29 | 浙江大学 | Preparation method of non-sizing nano-calcium phosphate powder for medical slow release metal ion |
| CN101507841B (en) * | 2009-03-30 | 2012-11-07 | 西南交通大学 | Preparation method of inorganic calcium phosphate salt/biodegradable polymer fiber film composite material |
| CN101773690A (en) * | 2010-03-11 | 2010-07-14 | 浙江大学 | Polylactic acid based/20nm calcium phosphate composite stent material and preparation method thereof |
| CN102247624A (en) * | 2011-01-21 | 2011-11-23 | 北京中奥汇成生物材料科技有限公司 | Absorbable bone screw and preparation method thereof |
| CN104524637A (en) * | 2014-06-03 | 2015-04-22 | 东莞天天向上医疗科技有限公司 | High-molecular biological ceramic composite nanometer particle biodegradable stent and manufacturing method thereof |
| CN105013006A (en) * | 2015-06-24 | 2015-11-04 | 东莞天天向上医疗科技有限公司 | Bioabsorbable bone repair material and its use and manufacturing method |
| CN107126582A (en) * | 2017-06-02 | 2017-09-05 | 北京航空航天大学 | The preparation of amorphous calcium phosphate/PLA electrospun scaffolds |
| CN108815579A (en) * | 2018-07-09 | 2018-11-16 | 苏州市贝克生物科技有限公司 | Nanocomposite and preparation method thereof |
| CN111744058A (en) * | 2019-03-28 | 2020-10-09 | 施吉生技应材股份有限公司 | Method for producing bone plate |
| CN111643736A (en) * | 2020-05-28 | 2020-09-11 | 北京市春立正达医疗器械股份有限公司 | Composite material for interface screw and preparation method thereof |
| CN112546294A (en) * | 2020-12-03 | 2021-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of polyanhydride modified controllable biodegradable calcium phosphate bone cement, product and application thereof |
| CN112933300A (en) * | 2021-02-03 | 2021-06-11 | 北京天星博迈迪医疗器械有限公司 | Absorbable fixed graft and preparation method thereof |
-
2003
- 2003-08-08 CN CN 03142161 patent/CN1270783C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1485098A (en) | 2004-03-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ju et al. | High-performance porous PLLA-based scaffolds for bone tissue engineering: Preparation, characterization, and in vitro and in vivo evaluation | |
| Jayanth et al. | A review on biodegradable polymeric materials striving towards the attainment of green environment | |
| CN1270783C (en) | Degradable nanometer composite material for biological and medical use | |
| Feng et al. | In situ generation of hydroxyapatite on biopolymer particles for fabrication of bone scaffolds owning bioactivity | |
| Liu et al. | High performance high-density polyethylene/hydroxyapatite nanocomposites for load-bearing bone substitute: fabrication, in vitro and in vivo biocompatibility evaluation | |
| Wei et al. | 3D-printed hydroxyapatite microspheres reinforced PLGA scaffolds for bone regeneration | |
| Boccaccini et al. | Bioresorbable and bioactive polymer/Bioglass® composites with tailored pore structure for tissue engineering applications | |
| CN1939543A (en) | Composite stand materials of polylactic acid base/nano-hydroxy-apatite and its production | |
| KR20170126416A (en) | Injectable composition for filler comprising porous biodegradable microspheres and water soluble natural polymers | |
| CN1792379A (en) | Method for preparing organic and inorganic nanometer composite organization engineering stent material by using thermal phase separation | |
| Zhu et al. | An injectable hydroxyapatite/poly (lactide-co-glycolide) composite reinforced by micro/nano-hybrid poly (glycolide) fibers for bone repair | |
| CN102397589A (en) | Bio-absorbable medical compound material and preparation method thereof | |
| CN1314462C (en) | Degradable biomedicine composite material in nanometer structure and its prepn process | |
| CN102397588A (en) | Porous magnesium alloy three-dimensional reinforced absorbable medical compound material and preparation method thereof | |
| CN111068106A (en) | Medical degradable antibacterial composite material and preparation method and application thereof | |
| CN101053673A (en) | High strength and tenacity degradable strontium calcium superphosphate composite bone cement and its preparation method | |
| KR100941511B1 (en) | Fabrication of biodegradable biopolymer/calcium phospate hybrid scaffold having high functional biodegradability | |
| CN1403165A (en) | Active composition for repairing hard tissue and its prepn | |
| Ali et al. | Effect of carbon based fillers on properties of Chitosan/PVA/βTCP based composite scaffold for bone tissue engineering | |
| Oyedeji et al. | Fabrication and characterization of hydroxyapatite-strontium/polylactic acid composite for potential applications in bone regeneration | |
| CN102552993B (en) | Magnesium alloy sheet-reinforced absorbable intrabony fixing composite material and preparation method thereof | |
| CN108096629B (en) | Polymethyl methacrylate bone cement and preparation method thereof | |
| WO2003103925A1 (en) | Co-continuous phase composite polymer blends for in-vivo and in-vitro biomedical applications | |
| CN1403167A (en) | Hard tissue repairing material and its prepn | |
| CN1242818C (en) | Degradable composite support frame and its preparing process |
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 | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060823 |