A kind of novel degradable bone implant and preparation method thereofTechnical field
The present invention relates to medical bone implanting appliance field more particularly to a kind of novel degradable bone implant and its preparation sidesMethod.
Background technique
When fracture, disease equivalent damage occurs in bone tissue, need to carry out bone implant.Bone implant mainly has self bone implantObject, allogeneic bone implant and biomaterial bone implant., because of limited amount, clinical application is restricted for the above two.MeshBefore, bone implant made of biomaterial is clinically commonly used, this biomaterial includes non-degradable and degradation material.It can notDegradable material bone implant as made of stainless steel, titanium alloy, PEEK etc. needs second operation to take due to non-degradable in vivoOut.In addition the problems such as metal bone implant be easy to cause stress shielding, although PEEK material mechanics and bone tissue are similar, millIt reams the particle fallen and be easy to cause the complication such as inflammation.Degradation material bone implant as made of PGA, PLLA, magnesium alloy etc.,Its catabolite after being implanted into generates adverse effect to tissue.In addition, degradable biological ceramics bone implant, because of its brittlenessGreatly, the disadvantages of bending strength is insufficient receives certain limitation in clinical application.
Fusion device is a kind of clinically common bone implant, and the research about degradable fusion device is very more in recent years,Such fusion device is mainly made of pure magnesium, magnesium alloy, polylactic acid or its copolymer, bioceramic etc..For example, Chinese patent201310388513.X discloses a kind of Invasive lumbar fusion device, by poly-DL-lactic acid, Poly-L-lactide/ethanol copolymer, hydroxyl phosphorusLime stone and tricalcium phosphate are made, and have high-intensitive, good bone-inducting active, can degradable absorption in vivo, but still deposit dropSolve the problems such as rate is partially slow, catabolite is in acid.
Chinese patent 201410073104.5 discloses a kind of spinal fusion device that degradation rate is controllable, component and weightPercentage are as follows: lithotroph ceramics 1%-10%, magnesium or magnesium alloy 10%-80%, remaining is degradable high polymer, canDegraded macromolecular material is coated in surface, keeps its degradation rate controllable.
Based on this, a kind of good mechanical properties are designed and developed out, can degradable absorption and degradation rate and new bone growthIt matches, the bone implant of processus styloideus radii fusion rate, is one of the target that Recent study is pursued.
Summary of the invention
The purpose of the present invention is to provide a kind of novel degradable bone implants and preparation method thereof, take pressurization preparationAfter be placed on thermo-humidistat cabinet processing, and degradable metal is added in bone implant.Degradable bone implant of the invention is alsoIncluding degradable macromolecule coating, the degradation rate of bone implant is controlled by adjusting the thickness of coating.Gather around bone implantThere is processus styloideus radii fusion rate, degradable can absorb.Degradable bone implant of the invention includes silicon-containing compound, is being degradedCheng Zhong, bone implant surface can generate the porous gel layer of rich Si-O-Si.It can be generated on silicon gel layer surface a large amount of negatively chargedSi-OH, with different types of protein pass through hydrogen bond and ion amine key (- Si-O-H3N+) combine form highdensity albumenAbsorption, to promote extracellular response.In addition, the metal ion that silicon gel layer can be formed with degradation generates chelation, dropFreedom of the low metal ion in body fluid, mitigates the toxicity of these ion abnormal increases generation, so that biocompatibility is improved,Promote Bony union.
The technical solution adopted by the present invention to solve the technical problems is:
A kind of novel degradable bone implant, the bone implant are made by solidifying after pulvis and liquor mixing pressurization, instituteIt is composed of the following components to state pulvis: the phosphate of 32-70wt%, the metal oxide of 28-65wt% and 1-15wt% it is siliceousThe liquid-solid ratio of compound, the liquor and pulvis is 0.1-0.5ml/g.
The purpose of the present invention can also be further realized by technical solution below:
Preferably, the phosphate include potassium dihydrogen phosphate, sodium dihydrogen phosphate, calcium dihydrogen phosphate, ammonium dihydrogen phosphate oneOr mixtures thereof kind.
Preferably, the metal oxide includes magnesia, aluminum oxide, iron oxide, di-iron trioxide, four oxidations threeIron, zinc oxide or zirconium oxide.
Preferably, the pulvis further includes degradable rush adhesives.
Preferably, the degradable rush adhesives includes beeswax, Sodium Hyaluronate, gelatine, carbohydrate or derivatives thereof.
Preferably, the silicon-containing compound includes silica and/or silicate.
Preferably, the phosphate further includes calcium phosphate, and the calcium phosphate includes type alpha tricalcium phosphate, bata-tricalcium phosphateOr mixtures thereof one kind.
Preferably, the liquor includes or mixtures thereof deionized water, sodium chloride solution, one kind of phosphoric acid solution.
Preferably, the bone implant further includes degradable metal framework or metal inner support, the degradable goldBelong to includes pure magnesium or magnesium alloy.
Preferably, the bone implant further includes degradable high polymer material, and the degradable high polymer material includes poly-Glycolic, polylactic acid or its copolymer.
A kind of preparation method of above-mentioned novel degradable bone implant, the bone implant is by pulvis and liquor mixing noteIt penetrates after pressurizeing to solidify and be made, the pulvis is composed of the following components: the metal oxidation of the phosphate, 28-65wt% of 32-70wt%The liquid-solid ratio of the silicon-containing compound of object and 1-15wt%, the liquor and pulvis is 0.1-0.5ml/g, and the pulvis further includes canDegradation promotees adhesives, and the degradable rush adhesives includes beeswax, Sodium Hyaluronate, gelatine, carbohydrate or derivatives thereof, stepIt is rapid as follows:
A. paste is obtained after the pulvis and liquor being mixed in 0.1-0.5ml/g ratio；
B. paste is injected in mold, and keeps injection pressure >=5atm；
C. to paste curing and demolding, bone implant is obtained；
D. by bone implant be placed on 37 DEG C of temperature, humidity 50-100% thermo-humidistat cabinet in >=for 24 hours.
Preferably, it before the step a, first by the degradable intermetallic composite coating at silk, item, frame or netted, and putsEnter mold.
Preferably, further comprising the steps of between the step c and d:
(1) degradable high polymer material is dissolved in organic solvent and obtains solution A；
(2) solution A is coated on by bone implant surface, bone implant surface coating layer thickness using spray coating method or dip coatingAbout 0.01-2mm.
Preferably, before the step a, first degradable high polymer material is previously added in pulvis, and is uniformly mixed.
Compared with the existing technology, advantages of the present invention and progress are as follows:
1. degradable bone implant of the invention is in degradation process, surface can generate porous gel layer, in silicon gel layerSurface will form highdensity protein adsorption, to promote extracellular response.In addition, silicon gel layer can be generated with metal ionChelation reduces freedom of the metal ion in body fluid, mitigates the toxicity of these ion abnormal increases generation, to improveBiocompatibility promotes Bony union.
2. degradable bone implant of the invention takes pressurization measure in injection mold process, and by the bone after demouldingImplantation material is placed on thermo-humidistat cabinet processing, so that degradable bone implant obtained has good mechanical property.
3. degradable bone implant of the invention further includes degradable metal, degradable metal be processed to silk, item, frame orIt is netted to be uniformly distributed in bone implant, it can further promote the mechanical property of degradable bone implant.
4. degradable bone implant of the invention can generate suitable magnesium ion in degradation process, bone group can be promotedKnit growth.In addition, degradable bone implant of the invention can also be planted by the content or thickness of control polymeric coating layer, control boneEnter the degradation rate of object, to match bone growth.
Detailed description of the invention
Fig. 1 is the degradable bone filler particles schematic diagram of φ 3x3 of the invention.
Fig. 2 is the structural schematic diagram of the degradable fusion device of the invention containing magnesium alloy frame.
Fig. 3 is the structural schematic diagram of the degradable fusion device of the invention containing pure magnesium rod.
Fig. 4 is the structural schematic diagram of the degradable fusion device of the coating of the invention containing polylactic acid.
Fig. 5 is the structural schematic diagram of the degradable bone stick of the filler of the invention containing polyglycolic acid.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, as follows in conjunction with drawings and embodimentsThe present invention is described in detail.
Pulvis and liquor exemplary formulations of the invention is as follows:
It is formulated 1.:
Pulvis is prepared by following weight percent (wt%):
Liquor is deionized water, and the liquid-solid ratio of pulvis and liquor is 0.2ml/g.
It is formulated 2.:
Pulvis is prepared by following weight percent (wt%):
Liquor is physiological saline, and the liquid-solid ratio of pulvis and liquor is 0.22ml/g.
It is formulated 3.:
Pulvis is prepared by following weight percent (wt%):
Liquor is phosphoric acid solution, and the liquid-solid ratio of pulvis and liquor is 0.25ml/g.
It is formulated 4.:
Pulvis is prepared by following weight percent (wt%):
Liquor is deionized water, and the liquid-solid ratio of pulvis and liquor is 0.16ml/g.
It is formulated 5.:
Pulvis is prepared by following weight percent (wt%):
Liquor is physiological saline, and the liquid-solid ratio of pulvis and liquor is 0.32ml/g.
Foregoing exemplary formula is some optimization formula ratios of the invention, is not intended to restrict the invention.
Embodiment 1
Fig. 1 is degradable bone filler particles schematic diagram prepared by the present invention, and specific preparation process is as follows:
A. paste is obtained after 1. the pulvis and liquor being mixed by formula；
B. paste is injected in the mold of φ 3x3, and keeps injection pressure 8atm；
C. to paste curing and demolding, bone filler particles are obtained；
D., bone filler particles are placed on to 28h in the thermo-humidistat cabinet of 37 DEG C of temperature, humidity 60%.
Prepared degradable bone filler particles can be used for the filling of bone defect position.
Embodiment 2
Fig. 2 is the structural schematic diagram of the degradable fusion device 1 of the metal framework 2 prepared by the present invention containing magnesium alloy, specificallyPreparation step is as follows:
A. magnesium alloy is processed into frame, and is put into mold.
B. paste is obtained after 2. the pulvis and liquor being mixed by formula；
C. paste injection is had in the mold of magnesium alloy frame, and keeps injection pressure 15atm；
D. to paste curing and demolding, degradable fusion device is obtained；
E., degradable fusion device is placed on to 48h in the thermo-humidistat cabinet of 37 DEG C of temperature, humidity 80%.
Prepared can be used for various fusions for degradation fusion device.
Embodiment 3
Fig. 3 is the structural schematic diagram of the degradable fusion device 1 of the metal inner support 3 prepared by the present invention containing pure magnesium rod, toolPreparation step is as follows:
A. into strips by the processing of pure magnesium, and it is put into mold.
B. paste is obtained after 3. the pulvis and liquor being mixed by formula；
C. paste injection is had in the mold of pure magnesium rod frame, and keeps injection pressure 12atm；
D. to paste curing and demolding, degradable fusion device is obtained；
E., degradable fusion device is placed on to 36h in the thermo-humidistat cabinet of 37 DEG C of temperature, humidity 90%.
Prepared can be used for various fusions for degradation fusion device.
Embodiment 4
Fig. 4 is the structural schematic diagram of the degradable fusion device 1 of coating containing polylactic acid prepared by the present invention 4, specific preparation stepIt is rapid as follows:
A. paste is obtained after 4. the pulvis and liquor being mixed by formula；
B. paste is injected in fusion device mold, and keeps injection pressure 10atm；
C. to paste curing and demolding, degradable fusion device is obtained；
D., polylactic acid is dissolved in the solution A that 0.1g/ml is formed in acetone；
E. solution A is coated on by degradable fusion device surface, surface covering thickness about 0.05mm using dip coating.
F., degradable fusion device is placed on to 36h in the thermo-humidistat cabinet of 37 DEG C of temperature, humidity 90%.
Prepared can be used for various fusions for degradation fusion device.
Embodiment 5
Fig. 5 is the structural schematic diagram of the degradable bone stick 5 of filler containing polyglycolic acid prepared by the present invention 6, specific preparation stepIt is rapid as follows:
A. polyglycolic acid powder is added and is formulated the 5. described pulvis, mass ratio 0.1: 1, and be uniformly mixed；
B. paste is obtained after pulvis and liquor being mixed；
C. paste is injected in fusion device mold, and keeps injection pressure 6atm；
D. to paste curing and demolding, degradable bone stick is obtained；
E. degradable bone stick is placed in the thermo-humidistat cabinet of 37 DEG C of temperature, humidity 100% for 24 hours.
The prepared bone stick that can will drop can be used for the filling etc. of nail hole.
Finally it should be noted that the foregoing is merely preferred embodiment of the invention, it is not limited to thisInvention, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in this hairWithin bright protection scope.