Background technology
According to clinical data statistics display, annual about 20,000,000 examples in the number only fractured in the osteopathia whole nation, needing the case load of surgical menopause to account for 15%, about 3,000,000 examples, the current overwhelming majority is all with fixing in metal.Current domestic use can absorb product and is mostly used for non-bony site case of weighing and probably has 390,000 examples/year, only account for about the 13% of whole market, if the product for load-bearing bone can be produced, this product keeps corresponding support strength when of support in vivo, the needs of osteogenesis can also be coordinated, control degradation speed with osteogenesis well, be then preferable product in orthopaedics internal fixation material.
Degradable bone internal fixation material material category is a lot, has mineral substance, macromolecular material and degradable metal material such as magnesium alloy and ferroalloy etc..Common medical can have polylactic acid (PLA), polyglycolic acid (PGA) and copolymer (PLGA), polycaprolactone and poly-dioxanone etc. by solving macromolecular material, and wherein polylactic acid (PLA), polyglycolic acid (PGA) and copolymer (PLGA) application thereof are the most extensive.Wherein polylactic acid includes PLLA and PDLA, the degraded of the polylactic acid of high molecular slowly, in vivo can longer-term persistence, the local sour environment produced after polylactic acid inner fixing member vivo degradation in addition, easily cause osseous tissue aseptic inflammation, have impact on the formation of new bone；And polylactic acid fixture mechanical strength is not enough, lack synosteosis ability.Therefore, polylactic acid modified having become study hotspot improving its correlated performance, modified main purpose is the mechanical strength for reinforcing material, controls its degradation rate and neutralize the acidity of catabolite so that it is have more preferable biocompatibility.
Degradable magnesium alloy material is the degradation material that recent research is hotter, and magnesium is the element that body metabolism is required, and the content in human body is only second to potassium, sodium, calcium, constitutes about the half of internal all magnesium in osseous tissue.Research thinks that magnesium is the cofactor of many enzymes, has stabilized DNA and RNA structure；Magnesium is maintained between 0.7 and 1.05mmol/L by kidney and intestinal in vivo；Magnesium can stimulate new bone growth, and histocompatibility is good.The major defect of magnesium is low corrosion resistance, and in the physiological environment of pH (7.4-7.6), magnesium has the strongest reduction thus loses mechanical integrity before tissue fully healing, and produces the hydrogen that body cannot absorb in time.So reducing the consumption of magnesium metal material, the magnesium base alloy of controlled degradation, the hydrogen produced in magnesium degradation process is made to be fallen to have the most real meaning by tissue fluid metabolism.
Such as Invasive lumbar fusion device (cage), has been widely used in spinal fusion, it is to avoid the generation of autologous bone transplanting related complication.Present stage, for the mainly tradition fusion device of clinical intervertebral fusion, including metal class, polyether-ether-ketone (PEEK) class, carbon fiber class etc..But tradition Invasive lumbar fusion device has the existence of the related complications such as stress shielding, sedimentation, pseudoarticulation formation, affects postoperative effect.Elastic modelling quantity and nonabsorable that these complication are largely superfluous with tradition fusion device are relevant.Compared to tradition Invasive lumbar fusion device, absorbable interbody cage becomes the focus in clinical research application because of advantages such as its less stress-shielding effect, good x-ray permeability, degradability and the generations increasing bone conduction and promotion osteogenic response.
Preferably orthopaedics implants degradable internal fixation material should be to have enough bending strengths and comprcssive strength in the period needing support function, later stage autologous osteoplastic during can fast degradation, do not affect the growth of autologous bone, the catabolite of composite of the present invention reacts due to the neutralization of magnesium hydroxide and lactic acid, more accelerate the fast degradation of later stage polylactic acid, solve in clinical practice owing to polylactic acid produces the problem that acidity accumulation causes aseptic inflammation during degraded, due to the degraded of early stage magnesium alloy, polylactic acid expansion the most slightly further strengthens the support function of composite, there is good potential applicability in clinical practice.
Summary of the invention
The invention discloses fixing composite material in a kind of high-strength degradable bone, by filled high polymer material in magnesium-alloy tube, forming the composite of high intensity, one of catabolite is magnesium lactate, and its comprcssive strength is more than 200MPa, bending strength is more than 120Mpa, by weight percentage, wherein degradable magnesium alloy pipe is 5～70%, and surplus is macromolecular material, wherein the macromolecular material preferred viscosity-average molecular weight polylactic acid more than 150,000, specifically includes PLLA, PDLA and PLGA.
In the magnesium alloy that the magnesium-alloy tube of the present invention is used, the content of pure magnesium is more than 90%, weight ratio, remaining adding ingredient is ferrum, copper, zinc, cobalt, manganese, chromium, selenium, iodine, nickel, fluorine, molybdenum, vanadium, stannum, silicon, strontium, boron, rubidium, arsenic, silver, a kind of combination of or many Zhang Yuansu, each addO-on therapy percentage by weight is: ferrum 0-2.0%, copper 0-2.0%, zinc 0-2.0%, cobalt 0-2.0%, manganese 0-2.0%, chromium 0-2.0%, selenium 0-2.0%, iodine 0-2.0%, nickel 0-2.0%, fluorine 0-2.0%, molybdenum 0-2.0%, vanadium 0-2.0%, stannum 0-2.0%, silicon 0-2.0%, strontium 0-2.0%, boron 0-2.0%, rubidium 0-2.0%, silver 0.1～4%；Including: one or both combinations in high purity iron (purity is more than 99.0%), high purity magnesium (purity is more than 99.0%), Mg-Fe alloy (percentage by weight is 1: 0.01-10), Mg-Zn based alloy (percentage by weight is 1: 0.01-1), magnesium calcium alloy (percentage by weight is 1: 0.01-1), Magnesium-aluminum alloys (percentage by weight is 1: 0.01-0.1).Wherein Mg-Fe alloy (percentage by weight preferably 1: 0.01-0.1), Mg-Zn based alloy (percentage by weight preferably 1: 0.01-0.1), such as: Mg-Nd-Zn-Zr, Mg-Zn-Mn, Mg-Zn-Mn-Se-Cu alloy, Zn content is 3.5wt%, Mn content is 0.5-1.0wt%, Se content is 0.4-1.0wt%, Cu content is 0.2-0.5wt%, Mg surplus；Magnesium calcium alloy (percentage by weight preferably 1: 0.01-0.1), such as: (percentage by weight is preferably 1: 0.01-0.1 for Mg-Zn-Ca-Fe, Magnesium-aluminum alloys, such as: aluminum (Al): 2.0-3.0wt.%, zinc (Zn): 0.5-1.0wt.%, manganese (Mn), Mg surplus.The macromolecule polymer material of the present invention, selected from polyglycolic acid, polylactic acid, PLLA, degradable medical polyurethane, poly-hydroxy acrylate, poly-to dioxane ketone, condensing model, poly phosphazene, polymer-amino-acid, one or more combination in any in poly-β-hybroxybutyric acid and hydroxypentanoic acid fat and copolymer thereof, degradable ceramics can be injected, composition is hydroxyapatite, strontium containing hydroxyapatite, Silicon-Substituted Hydroxyapatite, one or more combination in any in bata-tricalcium phosphate and phosphoric acid oxygen four calcium, preferably polyglycolic acid, polylactic acid, PLLA, poly lactic acid type degradable medical polyurethane, more preferably Poly-L-lactic acid and PDLLA, its viscosity-average molecular weight is more than 150,000.
The preparation method of the high-strength degradable composite of the present invention:
One of its preparation method:
Polymer P LLA is dissolved in dichloromethane or chloroform and makes the fluid solution that percentage composition is 15-30%, inject in the magnesium alloy pipe that Passivation Treatment is good, add heat fusing, the evacuation bubble that volatilized by solvent is extracted out and be get final product, and the percentage by weight of wherein magnesium-alloy tube: PLLA is (0.1: 1)；
The two of its preparation method:
Being loaded in the magnesium alloy pipe that Passivation Treatment is good by Poly-L-lactic acid powder, add heat fusing, bubble is extracted out and get final product by evacuation, wherein magnesium-alloy tube: the percentage by weight of PLLA is (0.1: 1)；
The three of its preparation method:
Being melted by polymer P LLA, inject in the good magnesium alloy hollow tube of Passivation Treatment by injector or injection machine, cooling molding both obtained, and the percentage by weight of wherein magnesium-alloy tube: PLLA is (0.1: 1)；；
The composite pipe one of above-mentioned three kinds of methods prepared, is hot pressed into Sandwich board stock pressure 10～150Mpa, furnace temperature 100～140 DEG C, stock, by Digit Control Machine Tool or laser engraving equipment or finishing become variously-shaped in fixing medical apparatus and instruments.
Wherein magnesium alloy pipe magnesium and various alloy, according to clinical degradation time length need carry out surface process, processing method can be the method mentioned in any open source literature, such as: the process of phosphate-permanganate, such as: the process of bichromate, such as: the process of phosphate-molybdate, stannate, cobaltatess etc., organic transformation film, rare earth etc. are conversional solution and fluohydric acid gas conversion infusion method etc..
Fixing composite material in the high-strength bone of the present invention, GUSUIPIAN in fracture fixation reparation, bone connect fixes, bone piece in osteopathy is fixed, specifically include vertebrae mixer, prepare hone lamella, nail, bone screw, spicule, rib nail, bone rod, internal fixation of spine equipment, patella fracture fixator, bone wax, breastbone fixing nail, medullary substance bone screws, the various bone renovating material of packing ring.
Fixing composite material in the high-strength bone of the present invention, it is characterized in that adding developing agent, specifically by zirconium dioxide, diodone and pure blanc fixe, one of them is dispersed in macromolecular material, add in composite with macromolecular material, wherein Operand is selected from ion-type: such as cardiografin or nonionic: such as the one in iohexol, Iopromide (iopromide) and B-15000 (iopamidol), preferably titanium dioxide zirconium powder or pure blanc fixe, more preferably titanium dioxide zirconium powder.Addition weight must be the 5-30% of macromolecular material, preferably 10-20%.
We once studied the poly-lactic acid material of magnesium base alloy surface-coated different-thickness, result of study shows linear relationship do not occur between the degraded of the thickness directly coated by polylactic acid and magnesium silk, is therefore difficult to prepare the magnesium base alloy polylactic acid medical material of controlled degradation.We have passed through research repeatedly, magnesium alloy is made tubing, filling polylactic acid family macromolecule material, make the composite construction of reinforced cement concrete, on the one hand making the control of trace elements in tubing by magnesium alloy controls the degradation time of material, to adapt to the needs that clinical different parts uses the degradation time of material, on the other hand the molecular weight Poly-L-lactic acid more than more than 150,000 is filled, further enhance the intensity of composite, thus improve the mechanical strength of material, to be applicable to the filling needs of human body different parts.The controlled degradation of the result of study display present invention of external degradation can absorb orthopedic implanting material and has good clinical compliance, has practical value widely.The magnesium hydroxide produced in degradation process and lactic acid neutralization, define the nutritional labeling magnesium lactate that human body easily absorbs, and with deficiency magnesia in supplement, to preventing various grass tetany, strengthening vitality has remarkable result.
In the high-strength bone of the present invention, fixing composite material can increase antiinflammatory or promote the ingredient of osteogenesis: such as Bone formation albumen, specifically includes: bone morphogenetic proteins, BMP2, the BMP7 etc. in such as BMP series；nullAntiproliferative can also be increased、Anti-migration、Angiogenesis inhibitor、Anti-inflammatory、Antiinflammatory、Or treatment osteoporosis and the slow-released carrier for the treatment of cells of tumorous bone，Specifically include the group of following material: sirolimus、Everolimus、Pimecrolimus、Somatostatin、Tacrolimus、Roxithromycin、Daunomycin、Ascosin、Ba Foluo mycin、Abboticine、Midecamycin、EN-141、ConA、Clarith、Triacetyloleandomycin、Folimycin、Cerivastatin、Simvastatin、Lovastatin、Fluvastatin、Rosuvastatin、Atorvastatin、Pravastatin、Pitavastatin、Catharanthine、Vincristine、Vindesine、Vinorelbine、Etoposide、Teniposide、Nimustine、Carmustine、Luo Mositing、Cyclophosphamide、Estramustine、Alkeran、Ifosfamide、Trofosfamide、Chlorambucil、Bendamustine、Dacarbazine、Busulfan、Procarbazine、Treosulfan、Temozolomide、Phosphinothioylidynetrisaziridine、Doxorubicin、Aclarubicin、Epirubicin、Mitoxantrone、Idarubicin、Bleomycin、Ametycin、Dactinomycin、Methotrexate、Fludarabine、Fludarabine-5 '-dihydrogen orthophosphate、Cladribine、Mercaptopurine、Thioguanine、Cytosine arabinoside、Fluorouracil、Gemcitabine、Capecitabine、Polyenoid taxol、Carboplatin、Cisplatin、Oxaliplatin etc..