CN101856509A - Calcium magnesium injectable bone cement and preparation method and application thereof - Google Patents
Calcium magnesium injectable bone cement and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a product used for forming calcium magnesium injectable bone cement, comprising solid phase powder obtained by uniformly mixing composite phosphoric acid calcium salt and magnesium phosphate powder as well as curing solution obtained by dissolving dextrin and hydrophosphate in water. The invention also discloses a calcium magnesium injectable bone cement and preparation method and application thereof. The curing solution and solid phase powder in the product are uniformly mixed and blended into paste, thus obtaining water phase high efficiency scattering-resistant rapid curing bone cement capable of being injected with calcium magnesium and injectable product used for preparing bone tissue wound repairing. The invention is low in cost of raw materials, preparation method is simple, the obtained calcium magnesium injectable bone cement has strong scattering-resistance and rapid curing speed.
Description
Technical field
The invention belongs to medical repair materials field, relate to a kind of product that is used to form calcium magnesium injectable bone cement, a kind of calcium magnesium injectable bone cement and preparation method thereof and application, be particularly related to a kind of product that is used to form the efficient anti-collapsibility fast setting of water calcium magnesium injectable bone cement, the efficient anti-collapsibility fast setting of a kind of water calcium magnesium injectable bone cement and preparation method thereof and application.
Background technology
Some common clinically fracture, as radius far-end fracture, fracture of the tibial plateau, fracture of calcaneus, compression fracture of vertabral body etc., only need closed reduction, percutaneous injection bone renovating material just can carry out the defect repair treatment, avoid the cutting operation position, simplified operation process, and can reduce iatrogenic soft tissue injury and approach related complication, do not destroy and repair district's blood confession, to patient's wound minimum, expense is lower, is easy to be accepted by the patient.At present, the syringeability bone that develops efficient Wicresoft substitutes repair materials has become inevitable direction, and for satisfying the needs of clinical practice, injectable bone cement should have rational hardening time (being generally 8-20 minute), higher intensity and good anti-collapsibility performance.
Water injectable calcium phosphate bone cement (Injectable calcium phosphate cement, ICPC) owing to have the characteristic of " fixed-point injection, in-situ solidifying, bio-compatible, progressively degraded ", can obtain significant progress over nearly 10 years according to any plastotype of defect.Yet in order to obtain better injectable performance, with respect to conventional bone cement, the ICPC that minimally-invasive treatment is used has higher liquid-solid ratio, has caused the prolongation of hardening time.Meanwhile, because some ions and most of Organic substance have and stop or postpone the effect that cured product hydroxyapatite (HA) forms in the blood plasma, this makes that again the setting time of ICPC is more external much longer.Both being unfavorable for that operation carried out long hardening time, the ICPC slurry is broken up by operative site hemorrhage or having washed away, having worsened the anti-collapsibility performance of slurry then.If anti-collapsibility is bad, in being expelled to body before the after fixing, slurry with easily be etched and rare diffusing not molding after blood plasma or body fluid contact, finally influence the curing of slurry even limit its clinical practice.Particularly in the molding of percutaneous vertebral body, in a single day uncured micro-nano powder enters cardiovascular system with blood, then can cause blood vessel blockage, causes thrombosis and other complication.At present, this defective has greatly limited application (Biomaterials, 1996, the 17:1429-1435 of ICPC in clinical; Bioceramics, 1996,9:235-238).Therefore, be necessary on the basis of improving slurry anti-collapsibility performance, ICPC to be cured regulation and control.
The raising of anti-collapsibility performance can realize by the prescription that adds anti-collapsibility agent or change itself.(J Biomed Mater Res, 1997,36 (3): 393-399) in consolidation liquid, add sodium alginate, found that to put into water immediately after slurry is in harmonious proportion less defeated and dispersed, and can normally solidify such as Ishikaw.Its mechanism of action be calcium ion in sodium alginate and the slurry in conjunction with forming water-fast calcium alginate hydrogel, thereby give the slurry anti-collapsibility.(J Mater sci:Mater Med such as Takechi, 1996,7 (6):, make the syringeability of ICPC improve, but prolonged hardening time 317-322) by in ICPC, adding additives such as hydroxy methocel, carboxymethyl cellulose, chitosan acetate, chitosan lactate.(Journal of Inorganic Materials such as Wang Ying, 2006,21 (6): 1435-1442) agent joins ICPC as anti-collapsibility with cellulose, the slurry of finding preparation has good water repelling property, comprcssive strength is 20-30MPa, and cured product is HA, good biocompatibility, but be 50-55min hardening time, can't satisfy clinical actual needs.Above-mentioned anti-collapsibility agent has limited to a certain extent that water has improved the anti-collapsibility of slurry to the infiltration of slurry inside in the external environment, but still has certain powder body loss in solidification process, and has delayed the curing reaction time of slurry.
Dextrin be starchy material heated, acid or diastatic action issue estranged when separating with hydrolysis and transform the micromolecule intermediate material of generation.According to the preprocess method of starch and the difference of heat-treat condition, dextrin can be divided into white dextrin, yellow starch gum, Britain glue and maltodextrin.General acidity or the oxidative catalyst of adopting prepares white dextrin or yellow starch gum; Roasting direct and dextrin be called Britain glue.Maltodextrin is to be made through low hydrolysis, purification, spray drying by starch, does not contain the starch derivatives of free starch.Dextrin is soluble in water, have very strong adhesivity, good mobile and good water retention property, embossability is strong, can form water-solubility membrane and adhesives, but instead of part carboxymethyl cellulose (CMC) on toothpaste is produced, can improve the structure of toothpaste as thickening agent and stabilizing agent, and be widely used in fields such as medicine, food, papermaking, casting, wallpaper, label, stamp, adhesive tape, have excellent biological compatibility.
The magnesium phosphate bone cement (magnesium phosphate cement, MPC) early than 1945 as cement for building, afterwards the Brookhaven development in laboratory ammonium magnesium phosphate Binder Materials as remedial cement material fast.As a class inorganic reaction type adhesive, magnesium phosphate cement is similar to calcium phosphate bone cement (CPC), can solidify voluntarily under the Human Physiology environment, hydrated product is the biological Ore of ammonium magnesium phosphate class, good biocompatibility (Biomaterials, 2002,23:1283-1293).People such as Lilley prepared the structure that magnesium ion substitutes CaPs (Mg, Ca) Ps system think by adding the structure of the CaPs that magnesium ion can stable amorphous in the CaPs system, thus solidification process that can adjustment and control system and change the solidification intensity of system.Studies show that (Biomed Mater, 2008,3 (4): 1243-1249 for many years; J.R.Soc.Interface, 2010, doi:10.1098/rsif.2009.0559), MPC solidifies soon, early strength is high, biocompatibility and biological degradability are good, is a kind of ideal bone impairment renovation material.
Do not see the report that has dextrin raising ICPC slurry anti-collapsibility, MPC to be used to regulate and control anti-collapsibility type ICPC curing rate and anti-collapsibility performance up to now.
Summary of the invention
It is relatively poor that first purpose of the present invention is to overcome existing water injectable calcium phosphate bone cement anti-collapsibility, the blood that slurry is easily occurred by the art district gushes and breaks up or wash away and reduce the calcium phosphate bone cement syringeability and prolong deficiency such as hardening time, and a kind of product that is used to form calcium magnesium injectable bone cement is provided.
Another object of the present invention is to provide the method that is prepared calcium magnesium injectable bone cement by the said goods.
A further object of the present invention is to provide a kind of calcium magnesium injectable bone cement by method for preparing.
Last purpose of the present invention is to provide the application of above-mentioned calcium magnesium injectable bone cement.
The product that is used to form calcium magnesium injectable bone cement of the present invention comprises: the solid phase powder that is obtained by compound phosphoric acid calcium salt and magnesium phosphate powder uniform mixing; And by dextrin, the hydrophosphate consolidation liquid that obtains soluble in water.
According to the present invention, described dextrin is at least a in white dextrin, yellow starch gum, Britain glue and the maltodextrin.Described hydrophosphate is at least a in sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate and the potassium dihydrogen phosphate.The mass percent concentration of dextrin described in the described consolidation liquid is 1%～25%, the mass percent concentration 1%～18% of described hydrophosphate.
According to the present invention, the mean diameter of described compound phosphoric acid calcium salt comprises less than 10 microns: a kind of in calcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, hydroxyapatite, fluor-apatite, the calcium pyrophosphate or their mixture.The mass ratio of described compound phosphoric acid calcium salt and described magnesium phosphate powder is (9.5～0.5): (0.5～9.5).
The preparation method of calcium magnesium injectable bone cement of the present invention with the described consolidation liquid and the described solid phase powder mix homogeneously of the said goods, is in harmonious proportion and forms pastel; Wherein, the mass ratio of described consolidation liquid and described solid phase powder is (0.5～3): 1.Preferably, the mass ratio of described consolidation liquid and described solid phase powder is (0.5～0.9): 1.
According to the present invention, calcium magnesium injectable bone cement by method for preparing is provided, be the efficient anti-collapsibility fast setting of a kind of water calcium magnesium injectable bone cement (fast-setting and anti-washout injectable calcium magnesiium-based bone cement, fa-ICMB).
Product and the calcium magnesium injectable bone cement of the present invention that is used to form calcium magnesium injectable bone cement of the present invention all can be used for preparing osseous tissue repair in trauma injectable product.Described pastel can be filled into operative site by the syringe direct injection and use, and perhaps solidifies back formation firming body and recharge in the body in vitro human n-body simulation n environment, carries out clinical practice.The efficient anti-collapsibility fast setting of the water calcium magnesium injectable bone cement of the present invention's preparation is used for the treatment of osteoporosis and osseous tissue repair in trauma, be used in particular for auxiliary fixing, pulp cavity internal fixation, the bone cyst of common fracture such as distal radius, tibial plateau, calcaneus and fracture thereof and the bone tuberculosis postoperative is repaired, the root pipe is filled and vertebral body plastic operation, be particularly useful for treating collapse of vertebra and prevent spinal fracture.
The present invention has that cost of material is low, preparation is simple, be convenient to advantage such as operation technique, and the fa-ICMB anti-collapsibility of preparation is strong, syringeability good, and curing rate is fast.
Description of drawings
Fig. 1 has shown white dextrin to ICPC anti-collapsibility Effect on Performance, wherein, and (a) for not contain the ICPC (b) of white dextrin for containing white dextrin ICPC.
Fig. 2 is the X ray diffracting spectrum of the efficient anti-collapsibility fast setting of water calcium magnesium injectable bone cement firming body, wherein, (a) is the synthetic fa-ICMB of maltodextrin; (b) be the synthetic fa-ICMB of yellow starch gum; (c) be the synthetic fa-ICMB of white dextrin; (d) be the synthetic fa-ICMB of Britain glue; (e) be the synthetic ICPC of white dextrin.
Fig. 3 is the SEM picture of the efficient anti-collapsibility fast setting of water calcium magnesium injectable bone cement firming body.
Fig. 4 has shown the biocompatibility of the efficient anti-collapsibility fast setting of water calcium magnesium injectable bone cement firming body, wherein, and (a) for cultivating 1h; (b) for cultivating 2d; (c) for cultivating 3d.
The specific embodiment
The inventor is through extensive and deep research, be surprised to find that first, the compound phosphoric acid calcium salt of different proportionings is mixed the formation solid phase powder by a certain percentage with magnesium phosphate, the consolidation liquid of being prepared with the anti-collapsibility agent that contains good biocompatibility is in harmonious proportion again, can make the efficient anti-collapsibility fast setting of the water calcium magnesium injectable bone cement (fa-ICMB) of class toothpaste-like or thick paste.On this basis, the inventor has finished the present invention.
In the context of the present invention, described compound phosphoric acid calcium salt is not particularly limited, be the blended by a certain percentage mixture of several calcium phosphate, press the preparation of US5525148 and US5545254 disclosed method, described calcium phosphate is selected from: calcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, hydroxyapatite, fluor-apatite, calcium pyrophosphate, and the mean diameter of described complex calcium phosphate salt particle is less than 10 microns.Described magnesium phosphate powder is not particularly limited, and is alkali compounds and phosphatic mixture, presses the preparation of ZL 01 1 05373.9 and US 7094286B2 disclosed method, and described alkali compounds is that magnesium oxide is or/and calcium oxide; Described phosphate is dihydric phosphate, and described dihydric phosphate is at least a in Ammonium biphosphate, dalcium biphosphate, the APP.Described human body simulation body fluid is SBF, according to Kukubo T etc. (Kukubo T, J Biomed Mater Res, 1990,24:721-734) disclosed ion concentration is prepared.
Below in conjunction with specific embodiment, the present invention will be further described.Should be understood that following examples only are used to the present invention to be described but not to be used to limits the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.
Universal method
(1) anti-collapsibility rate
Prepared water calcium magnesium injectable bone cement is poured into syringe, No. 9 syringe needles of following termination, with push rod 37 ℃ human body simulation body fluid (simulated body fluid is released and placed to slurry, SBF) in, vibration in the shaken cultivation case (HZQ-F160, Taicang experimental facilities factory) of 120r/min.Take out after 10 minutes, oven dry, the percentage by weight that not defeated and dispersed firming body accounts for initial total firming body is calculated in weighing, is designated as the anti-collapsibility rate.
(2) hardening time
The bone cement slurry of above-mentioned preparation is made the sample of Φ 6mm * 5mm by mould, immerse SBF solution and in 37 ℃, 100% humidity environment, solidify, measure hardening time.
(3) initial viscosity
Adopt the flow graph of controlling strain (CR), by measuring different shear rate
The variation of following viscosities il obtains comprising the viscograph of initial viscosity, weighs the injectable performance of slurry with this.
(4) cell compatibility
The bone cement slurry of above-mentioned preparation is filled in the plastic mould, places 37 ℃, the simulation human body environment of 100% humidity, treat to take out after the full solidification, the demoulding obtains smooth lamellar (6 * 6 * 2mm of smooth surface
3).Above-mentioned firming body is sub-packed in vial, seals, standby after 20 minutes 120 ℃ of following high-temperature steam sterilizations.Under aseptic condition sample is put in 24 orifice plates bottom, every hole adds MG
63Cell suspension (1 * 10
4Individual/hole).Calf serum with 10% is a culture medium, sample is placed 37 ℃, 100% humidity, 5%CO
2Calorstat in cultivate, change a subculture every day.Utilize the growing state of inverted phase contrast microscope observation of cell behind cultivation 1h, 2d, the 3d.
Embodiment 1
Take by weighing compound phosphoric acid calcium salt powder (composition be calcium hydrogen phosphate, tetracalcium phosphate and the hydroxyapatite) 10g of particle diameter, as solid phase powder less than 10 μ m;
Take by weighing white dextrin 0.48g, sodium hydrogen phosphate 0.48g pours in the beaker that the 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate fully are dissolved in the deionized water, makes consolidation liquid;
Consolidation liquid is poured in the solid phase powder, in vessel, is uniformly dispersed, be in harmonious proportion evenly, obtain water injectable calcium phosphate bone cement with special-purpose modulation cutter.
The experiment condition of table 1 embodiment 2～12
The The performance test results of the water injectable calcium phosphate bone cement of embodiment 1～12 preparation is as shown in table 2.By table 2 as seen, after the agent of adding anti-collapsibility, the slurry that obtains has good syringeability in consolidation liquid, and initial viscosity increases, and the anti-collapsibility rate all increases, but is prolonging hardening time in varying degrees.Although add sodium hydrogen phosphate in consolidation liquid after, curing rate is accelerated, but still has surpassed rational hardening time.
Under the dual function of anti-collapsibility agent white dextrin and coagulant sodium hydrogen phosphate, after water injectable calcium phosphate bone cement is expelled to liquid phase, form line, the granulated slag that drops is less, and water body is limpid; When not adding white dextrin, slurry is expelled to can be defeated and dispersed in the water, the water body muddiness, as shown in Figure 1.Adopt x-ray diffractometer that the cured product of embodiment 1 is carried out material phase analysis, the result shows that the cured product of this system is mainly hydroxyapatite shown in Fig. 2 (e), and white dextrin is formed cured product does not have obviously influence.Effect after yellow starch gum, Britain glue, maltodextrin add is identical with white dextrin.
The performance of the water injectable calcium phosphate bone cement of table 2 embodiment 1～12 preparation
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??1 | ??98.34±0.91 | ??23.2±1.7 | ??151.22 |
| ??2 | ??65.42±1.46 | ??20.3±0.5 | ??79.85 |
| ??3 | ??74.77±1.58 | ??34.6±1.4 | ??96.32 |
| ??4 | ??91.56±0.79 | ??25.2±2.1 | ??171.22 |
| ??5 | ??65.52±1.76 | ??22.7±1.2 | ??89.15 |
| ??6 | ??61.23±1.44 | ??38.5±1.6 | ??98.97 |
| ??7 | ??93.11±1.34 | ??27.2±1.4 | ??193.78 |
| ??8 | ??60.48±1.20 | ??19.7±1.1 | ??95.13 |
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??9 | ??77.65±1.72 | ??36.5±1.2 | ??118.97 |
| ??10 | ??86.46±1.56 | ??25.2±1.0 | ??163.22 |
| ??11 | ??51.44±1.06 | ??18.4±1.3 | ??87.05 |
| ??12 | ??62.75±1.29 | ??33.5±1.2 | ??107.07 |
Embodiment 13
Take by weighing compound phosphoric acid calcium salt powder (composition be calcium hydrogen phosphate, OCP and the hydroxyapatite) 0.5g of particle diameter less than 10 μ m, magnesium phosphate powder 9.5g, dry type is mixed and is formed solid phase powder; Take by weighing white dextrin 1.2g, sodium hydrogen phosphate 1.04g pours in the beaker that the 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate fully are dissolved in the deionized water, makes consolidation liquid;
The consolidation liquid of above-mentioned preparation is poured in the solid phase powder, in vessel, be uniformly dispersed, be in harmonious proportion evenly, obtain having efficient anti-collapsibility and quick-setting water calcium magnesium injectable bone cement (fa-ICMB) with special-purpose modulation cutter.
Embodiment 14～24 repeats the experimental procedure of embodiment 13, and difference is experiment condition, and specifically as shown in table 3, The performance test results is as shown in table 4.
The experiment condition of table 3 embodiment 14～24
The performance of the water injectable calcium phosphate bone cement of table 4 embodiment 13～24 preparations
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??13 | ??99.34±0.87 | ??13.2±1.7 | ??141.78 |
| ??14 | ??82.58±1.54 | ??11.3±0.5 | ??79.85 |
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??15 | ??88.22±1.78 | ??22.9±1.3 | ??121.55 |
| ??16 | ??98.04±0.95 | ??14.0±1.2 | ??172.55 |
| ??17 | ??75.64±1.12 | ??11.9±0.8 | ??88.61 |
| ??18 | ??87.05±1.21 | ??27.2±1.9 | ??128.46 |
| ??19 | ??91.54±0.87 | ??14.0±1.7 | ??185.22 |
| ??20 | ??72.18±1.02 | ??13.2±0.5 | ??87.85 |
| ??21 | ??84.09±1.15 | ??30.9±1.3 | ??143.46 |
| ??22 | ??93.54±0.87 | ??16.0±1.7 | ??195.22 |
| ??23 | ??69.90±1.96 | ??14.7±0.7 | ??98.40 |
| ??24 | ??86.43±1.72 | ??32.8±1.9 | ??153.87 |
Embodiment 25
Take by weighing compound phosphoric acid calcium salt powder (composition be calcium hydrogen phosphate, OCP and the calcium pyrophosphate) 5g of particle diameter less than 10 μ m, magnesium phosphate powder 5g, dry type is mixed and is formed solid phase powder;
Take by weighing white dextrin 1.2g, sodium hydrogen phosphate 1.04g pours in the beaker that the 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate fully are dissolved in the deionized water, makes consolidation liquid;
The consolidation liquid of above-mentioned preparation is poured in the solid phase powder, in vessel, be uniformly dispersed, be in harmonious proportion evenly, obtain having efficient anti-collapsibility and quick-setting water calcium magnesium injectable bone cement fa-ICMB with special-purpose modulation cutter.
Embodiment 26～37 repeats the experimental procedure of embodiment 25, and difference is experiment condition, and specifically as shown in table 5, The performance test results is as shown in table 6.
The experiment condition of table 5 embodiment 26～37
The performance of the water injectable calcium phosphate bone cement of table 6 embodiment 25～37 preparations
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??25 | ??96.48±1.23 | ??16.2±1.3 | ??131.22 |
| ??26 | ??83.47±2.46 | ??13.3±0.5 | ??72.43 |
| ??27 | ??89.22±1.22 | ??27.9±1.7 | ??110.45 |
| ??28 | ??91.23±1.78 | ??17.8±1.90 | ??155.12 |
| ??29 | ??73.47±2.46 | ??13.3±0.5 | ??72.43 |
| ??30 | ??84.77±1.09 | ??29.1±1.9 | ??133.78 |
| ??31 | ??90.48±1.23 | ??16.2±1.6 | ??171.52 |
| ??32 | ??69.47±2.46 | ??14.5±0.5 | ??82.57 |
| ??33 | ??81.22±1.22 | ??33.1±0.7 | ??110.65 |
| ??34 | ??92.18±1.23 | ??17.7±1.6 | ??189.82 |
| ??35 | ??68.47±2.46 | ??15.5±0.5 | ??89.43 |
| ??36 | ??84.22±1.22 | ??34.1±0.7 | ??120.35 |
| ??37 | ??99.45±0.13 | ??15.40±1.28 | ??1437.4 |
Shown in table 4 and table 6, under the combined effect of MPC, dextrin and hydrophosphate, slurry has good syringeability, and initial viscosity increases, but curing rate obviously accelerates, and the anti-collapsibility rate obviously improves.
Adopt x-ray diffractometer that the cured product of embodiment 34 and 37 is carried out material phase analysis, as Fig. 2 (a) with (c), the result shows that the cured product of this system is mainly hydroxyapatite, tricalcium phosphate and unreacted magnesium phosphate, and maltodextrin and white dextrin are formed cured product does not have obviously influence.
Embodiment 38～42 repeats the experiment of embodiment 25, and difference is:
Embodiment 38: compound phosphoric acid calcium salt powder 9.5g, magnesium phosphate powder 0.5g; White dextrin 0.6g, maltodextrin 0.6g, sodium hydrogen phosphate 0.6g pours in the beaker that the 6g deionized water is housed.
Embodiment 39: compound phosphoric acid calcium salt powder 4g, magnesium phosphate powder 6g; White dextrin 0.96g, yellow starch gum 0.96g, sodium hydrogen phosphate 1.08g pours in the beaker that the 6g deionized water is housed.
Embodiment 40: compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, OCP and hydroxyapatite) 4g, magnesium phosphate powder 6g; White dextrin 0.14g, yellow starch gum 0.35g, Britain glue 0.12g, maltodextrin 0.35g, sodium hydrogen phosphate 0.02g, sodium dihydrogen phosphate 0.02g pours in the beaker that the 4g deionized water is housed.
Embodiment 41: compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite) 8g, magnesium phosphate powder 2g; Yellow starch gum 0.06g, potassium dihydrogen phosphate 0.96g pours in the beaker that the 6g deionized water is housed.
Embodiment 42: compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, tetracalcium phosphate and fluor-apatite) 7g, magnesium phosphate powder 3g; Britain glue 0.24g, dipotassium hydrogen phosphate 0.18g pours in the beaker that the 6g deionized water is housed.
The The performance test results of the water injectable calcium phosphate bone cement of embodiment 38～42 preparations is as shown in table 7.
The performance of the water injectable calcium phosphate bone cement of table 7 embodiment 38～42 preparations
| Embodiment | Anti-collapsibility rate (%) | Hardening time (min) | Initial viscosity (Pas) |
| ??38 | ??95.82±1.73 | ??14.7±1.3 | ??125.16 |
| ??39 | ??98.16±1.22 | ??11.5±1.8 | ??114.99 |
| ??40 | ??99.06±1.82 | ??12.9±1.5 | ??195.38 |
| ??41 | ??93.26±0.29 | ??15.60±1.91 | ??2345.7 |
| ??42 | ??98.42±0.36 | ??18.70±2.12 | ??2522.3 |
As shown in table 7, under the combined effect of MPC, dextrin and hydrophosphate, the hardening time of fa-ICMB is reasonable, and anti-collapsibility is strong, and slurry has good syringeability.Adopt x-ray diffractometer that the cured product of embodiment 41 is carried out material phase analysis, shown in Fig. 2 (b), the result shows that the cured product of this system is mainly hydroxyapatite, tricalcium phosphate and unreacted magnesium phosphate, and yellow starch gum is formed cured product does not have obviously influence.The cured product of sem observation embodiment 42, as shown in Figure 3, the result shows: the cured product of this system is mainly acicular hydroxyapatite, dicalcium phosphate and flaky unreacted magnesium phosphate, and shown in Fig. 2 (d), Britain glue is formed cured product does not have obviously influence.The employing cell culture experiments is carried out the biocompatibility analysis to the cured product of embodiment 40, and as shown in Figure 4, the result shows MG
63Cell has good adhesive attraction on fa-ICMB cured product surface, can not only sprawl fully, and propagation obviously has excellent biological compatibility.
In the water calcium magnesium injectable bone cement, add anti-collapsibility agent dextrin, dextrin has formed the solution of high viscosity and extensive chemical adhesion in aqueous solution on the one hand, physical absorption is in the fa-ICMB particle surface, the effect of playing fixing fa-ICMB granule and stoping moisture to infiltrate; The dextrin chain is in the bridging effect of particle surface on the other hand, intergranular electrostatic attraction effect of dextrin and fa-ICMB and Ca
2+With the anionic chelation in the dextrin, form compact texture, thereby play the anti-collapsibility effect.Introduce MPC in compound phosphoric acid calcium salt solid phase powder, after water mixed, the acidic components among the MPC are dissolving and generation ionization rapidly in water, discharges H
+, PO
4 3-, MPC neutral and alkali component MgO is subjected to water and H
+Attack after, particle surface dissolving generates Mg (OH)
2And Mg
2+While Mg
2+Dissociate out, with PO
4 3-Effect forms the magnesium phosphate crystallization, and Ca
2+Same PO dissociates out
4 3-Effect generates calcium phosphate-phosphate complex gel, has quickened the fa-ICMB curing proceeding.Along with the acceleration of fa-ICMB hydration reaction, form the gel reactant on the slurry surface and clogged the intergranular hole of fa-ICMB, can effectively improve the anti-collapsibility performance of system.
Preparation method of the present invention, on the basis of existing water injectable calcium phosphate bone cement, in system, add at least a anti-collapsibility agent in white dextrin, yellow starch gum, Britain glue and the maltodextrin first, utilize its stronger water conservation conformality, water-soluble formation high viscosity solution dexterously, form fine and close moisture film on the surface and with reactant and the efficient absorption of product and form the characteristics of extensive chemical adhesion, efficiently solve slurry and meet sepage and problem such as fall slag, be scattered even can not solidify, improved the anti-collapsibility ability of water injectable calcium phosphate bone cement.And on the basis of anti-collapsibility type water injectable calcium phosphate bone cement, in system, added coagulate soon, strong and magnesium phosphate early with good plasticity, biocompatibility and degradability.After consolidation liquid contacted, hydration reaction took place in fa-ICMB fast, formed the gel reactant and had clogged intergranular space and defective, and the collaborative formation that has promoted a great deal of contact point makes slurry have fast setting and high early strong characteristics.Its fast setting and high strong characteristics have early further promoted the raising of fa-ICMB anti-collapsibility performance again.After the efficient anti-collapsibility fast setting of the water calcium magnesium injectable bone cement aquation, its ultimate constituent is unbodied magnesium-phosphate complex gel and hydroxyapatite, similar to the inorganic constituents of calculi in vivo and human body hard tissue respectively, good biocompatibility, nonirritant.Show that the consolidation liquid that is equipped with by anti-collapsibility agent and hydrophosphate solution mixing system does not change the curing characteristics of protocalcium magnesium bone cement, and do not change the composition that solidifies the back hydrated product.
Preparation method of the present invention, dextrin and magnesium phosphate play synergistic function to the anti-collapsibility performance of system, and meanwhile magnesium phosphate also plays quick-setting effect to system.The fa-ICMB of preparation has performances such as anti-collapsibility, syringeability and fast setting concurrently.
The present invention arrives preparation tissue repair field with the application extension of dextrin, and this had both opened up new way for the performance of carrying the high contents of calcium and magnesium bone cement, had also opened up a new application for dextrin.The efficient anti-collapsibility fast setting of the water calcium magnesium injectable bone cement of preparation has that cost of material is low, preparation is simple, is convenient to advantage such as operation technique, and anti-collapsibility is strong, curing rate is fast, can use safely under blood/body fluid environment.When using the efficient suspending stabilized calcium phosphate bone cement of injectable of the present invention, can adopt direct mastic fill method, can be injected directly into the method for operative site by special syringe (changing syringe needle), method that also can the percutaneous vertebroplasty is perhaps by firming body bone grafting in art of curing molding in advance.
Claims (10)
1. a product that is used to form calcium magnesium injectable bone cement is characterized in that, comprising:
The solid phase powder that obtains by compound phosphoric acid calcium salt and magnesium phosphate powder uniform mixing; And
By dextrin, the hydrophosphate consolidation liquid that obtains soluble in water.
2. product according to claim 1 is characterized in that, described dextrin is at least a in white dextrin, yellow starch gum, Britain glue and the maltodextrin.
3. product according to claim 1 is characterized in that, the mass percent concentration of dextrin described in the described consolidation liquid is 1%～25%, the mass percent concentration 1%～18% of described hydrophosphate.
4. product according to claim 1 is characterized in that, the mass ratio of described compound phosphoric acid calcium salt and described magnesium phosphate powder is (9.5～0.5): (0.5～9.5).
5. product according to claim 1 is characterized in that, described hydrophosphate is at least a in sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate and the potassium dihydrogen phosphate.
6. product according to claim 1, it is characterized in that, the mean diameter of described compound phosphoric acid calcium salt comprises less than 10 microns: a kind of in calcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, hydroxyapatite, fluor-apatite, the calcium pyrophosphate or their mixture.
7. the preparation method of a calcium magnesium injectable bone cement is characterized in that, with the described consolidation liquid and the described solid phase powder mix homogeneously of each described product in the claim 1～6, is in harmonious proportion and forms pastel;
Wherein, the mass ratio of described consolidation liquid and described solid phase powder is (0.5～3): 1.
8. method according to claim 7 is characterized in that, the mass ratio of described consolidation liquid and described solid phase powder is (0.5～0.9): 1.
9. calcium magnesium injectable bone cement according to claim 7 or the preparation of 8 described preparation methoies.
10. as the application of each described product or the described calcium magnesium injectable bone cement of claim 9 in the claim 1～6, it is characterized in that, be used to prepare osseous tissue repair in trauma injectable product.
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| CN102552985A (en) * | 2012-01-20 | 2012-07-11 | 苏州大学 | Silk fibroin/calcium phosphate bone cement-based porous composite material and preparation method thereof |
| CN104107455A (en) * | 2013-04-19 | 2014-10-22 | 中国人民解放军第二军医大学 | Bone cement and slurry thereof |
| CN104591679A (en) * | 2015-01-31 | 2015-05-06 | 河南理工大学 | Modified magnesium oxychloride bone cement as well as preparation method and application thereof |
| CN104984388A (en) * | 2015-06-24 | 2015-10-21 | 苏州乔纳森新材料科技有限公司 | Skeletal system repairing material and preparation method thereof |
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Application publication date: 20101013 Assignee: Shanghai Rebone Biomaterials Co., Ltd. Assignor: East China University of Science and Technology Contract record no.: 2015310000019 Denomination of invention: Calcium magnesium injectable bone cement and preparation method and application thereof Granted publication date: 20140219 License type: Common License Record date: 20150130 |
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