the variation of lower viscosities il, obtains comprising the viscograph of initial viscosity, with this, weighs the injectable performance of slurry.

(4) cell compatibility

The bone cement slurry of above-mentioned preparation is filled in plastic mould, is placed in 37 ℃, the simulation human body environment of 100% humidity, after solidifying completely, take out, the demoulding obtains smooth lamellar (6 * 6 * 2mm of smooth surface³).Above-mentioned firming body is sub-packed in to vial, sealing, and at 120 ℃, high-temp steam sterilizing is standby after 20 minutes.Sample is put in to 24 orifice plate bottoms under aseptic condition, every hole adds MG₆₃cell suspension (1 * 10⁴individual/hole).10% the calf serum of take is culture medium, sample is placed in to 37 ℃, 100% humidity, 5%CO₂calorstat in cultivate, change a subculture every day.After cultivation 1h, 2d, 3d, utilize the growing state of inverted phase contrast microscope observation of cell.

Embodiment 1

Take compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, tetracalcium phosphate and the hydroxyapatite) 10g that particle diameter is less than 10 μ m, as solid phase powder;

Take white dextrin 0.48g, sodium hydrogen phosphate 0.48g, pours in the beaker that 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate are fully dissolved in deionized water, makes consolidation liquid;

Consolidation liquid is poured in solid phase powder, in vessel, is uniformly dispersed, with dedicated modulation cutter, be in harmonious proportion evenly, obtain water injectable calcium phosphate bone cement.

Embodiment 2～12 repeats the experimental procedure ofembodiment 1, and difference is experiment condition, specifically as shown in table 1.

The experiment condition of table 1embodiment 2～12

The performance test results of the water injectable calcium phosphate bone cement ofembodiment 1～12 preparation is as shown in table 2.From table 2, in consolidation liquid, add after anti-collapsibility agent, the slurry obtaining has good syringeability, and initial viscosity increases, and anti-collapsibility rate all increases, but is extending hardening time in varying degrees.Although add in consolidation liquid after sodium hydrogen phosphate, 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, water injectable calcium phosphate bone cement is expelled to after liquid phase, forms line, and the granulated slag dropping is less, and water body is limpid; While not adding white dextrin, slurry is expelled to can be defeated and dispersed in water, and water body is muddy, as shown in Figure 1.Adopt x-ray diffractometer to carry out material phase analysis to the cured product ofembodiment 1, result, as shown in Fig. 2 (e), shows that the cured product of this system is mainly hydroxyapatite, and white dextrin forms and has no significant effect cured product.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 2embodiment 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
				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 compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, OCP and the hydroxyapatite) 0.5g that particle diameter is less than 10 μ m, magnesium phosphate powder 9.5g, dry type is mixed and is formed solid phase powder; Take white dextrin 1.2g, sodium hydrogen phosphate 1.04g, pours in the beaker that 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate are fully dissolved in deionized water, makes consolidation liquid;

The consolidation liquid of above-mentioned preparation is poured in solid phase powder, in vessel, be uniformly dispersed, with dedicated modulation cutter, be in harmonious proportion evenly, obtain having Effective Anti collapsibility and quick-setting water calcium magnesium injectable bone cement (fa-ICMB).

Embodiment 14～24 repeats the experimental procedure ofembodiment 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 4embodiment 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
				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 compound phosphoric acid calcium salt powder (composition is calcium hydrogen phosphate, OCP and the calcium pyrophosphate) 5g that particle diameter is less than 10 μ m, magnesium phosphate powder 5g, dry type is mixed and is formed solid phase powder;

Take white dextrin 1.2g, sodium hydrogen phosphate 1.04g, pours in the beaker that 6g deionized water is housed, and fully stirs white dextrin, sodium hydrogen phosphate are fully dissolved in deionized water, makes consolidation liquid;

The consolidation liquid of above-mentioned preparation is poured in solid phase powder, in vessel, be uniformly dispersed, with dedicated modulation cutter, be in harmonious proportion evenly, obtain having Effective Anti collapsibility and quick-setting water calcium magnesium injectable bone cement fa-ICMB.

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

As 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 anti-collapsibility rate obviously improves.

Adopt x-ray diffractometer to carry out material phase analysis to the cured product of embodiment 34 and 37, as Fig. 2 (a) with (c), result shows that the cured product of this system is mainly hydroxyapatite, tricalcium phosphate and unreacted magnesium phosphate, and maltodextrin and white dextrin form and have no significant effect cured product.

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 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 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 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 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 6g deionized water is housed.

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 to carry out material phase analysis to the cured product of embodiment 41, as shown in Fig. 2 (b), result shows that the cured product of this system is mainly hydroxyapatite, tricalcium phosphate and unreacted magnesium phosphate, and yellow starch gum forms and has no significant effect cured product.The cured product of sem observation embodiment 42, as shown in Figure 3, result shows: the cured product of this system is mainly the unreacted magnesium phosphate of the hydroxyapatite of needle-like, dicalcium phosphate and lamellar, and as shown in Fig. 2 (d), Britain glue forms and has no significant effect cured product.Adopt cell culture experiments to carry out biocompatibility analysis to the cured product ofembodiment 40, as shown in Figure 4, result shows MG₆₃cell has good adhesive attraction on fa-ICMB cured product surface, can not only sprawl completely, and propagation obviously, has good biocompatibility.

In 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 fa-ICMB particle surface, the effect of playing fixing fa-ICMB granule and stoping moisture to infiltrate; Dextrin chain is in the bridging effect of particle surface on the other hand, the intergranular electrostatic attraction effect of dextrin and fa-ICMB and Ca²⁺with the chelation of anion in dextrin, form compact texture, thereby play anti-collapsibility effect.In compound phosphoric acid calcium salt solid phase powder, introduce MPC, after mixing with water, the acidic components in MPC dissolve and ionize rapidly in water, discharge H⁺, PO₄^3-, MPC neutral and alkali component MgO is subject to water and H⁺attack after, particle surface dissolves, and generates Mg (OH)₂and Mg²⁺.While Mg²⁺dissociate out, with PO₄^3-effect forms magnesium phosphate crystallization, and Ca²⁺free out same PO₄^3-effect generates calcium phosphate-phosphate complex gel, has accelerated fa-ICMB curing proceeding.Along with the acceleration of fa-ICMB hydration reaction, on slurry surface, form gel reactant 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 first at least one the anti-collapsibility agent in white dextrin, yellow starch gum, Britain glue and maltodextrin, utilize dexterously its stronger water conservation conformality, water-soluble formation high viscosity solution, on surface, form fine and close moisture film and with reactant and product efficient adsorption and form the feature of extensive chemical adhesion, efficiently solve slurry and meet sepage and fall slag, be scattered and the problem such as 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 fast solidifying, early strong and there is the magnesium phosphate of good plasticity, biocompatibility and degradability.After contacting with consolidation liquid, there is hydration reaction in fa-ICMB fast, forms gel reactant and clogged intergranular space and defect, and the collaborative formation that has promoted a great deal of contact point, makes slurry have fast setting and high early strong feature.Its fast setting and high early strong feature have further promoted again the raising of fa-ICMB anti-collapsibility performance.After the defeated and dispersed fast setting calcium magnesium injectable bone cement of water Effective Anti 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 not change the curing characteristics of protocalcium magnesium bone cement by anti-collapsibility agent and the standby consolidation liquid of hydrophosphate solution mixing system, and do not change the composition that solidifies rear 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 the performances such as anti-collapsibility, syringeability and fast setting concurrently.

The present invention is by the application extension of dextrin to preparation tissue repair field, and this had both opened up new way for putting forward the performance of high contents of calcium and magnesium bone cement, also for dextrin has been opened up a new application.The defeated and dispersed fast setting calcium magnesium injectable bone cement of water Effective Anti of preparation, has that cost of material is low, preparation is simple, be convenient to the advantages such as operation technique, and anti-collapsibility is strong, curing rate is fast, can under blood/body fluid environment, use safely.When the efficient suspending stabilized calcium phosphate bone cement of application injectable of the present invention, can adopt direct mastic fill method, can be injected directly into by special syringe (needle exchange head) method of operative site, also method that can percutaneous vertebroplasty, or by firming body bone grafting in art of curing molding in advance.

Claims

1. a product that is used to form calcium magnesium injectable bone cement, is characterized in that, comprising:

The solid phase powder being evenly mixed to get by compound phosphoric acid calcium salt and magnesium phosphate powder; And

By dextrin, the hydrophosphate consolidation liquid obtaining soluble in water;

Wherein, the mean diameter of described compound phosphoric acid calcium salt is less than 10 microns, comprising: the mixture in calcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, hydroxyapatite, fluor-apatite, calcium pyrophosphate; Described hydrophosphate is at least one in sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate and potassium dihydrogen phosphate; 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 mass percent concentration of dextrin described in described consolidation liquid is 1%～25%, the mass percent concentration 1%～18% of described hydrophosphate; The mass ratio of described consolidation liquid and described solid phase powder is (0.5～3): 1.

2. product according to claim 1, is characterized in that, described dextrin is at least one in white dextrin, yellow starch gum, Britain glue and maltodextrin.

3. a preparation method for calcium magnesium injectable bone cement, is characterized in that, the described consolidation liquid of the product described in any one in claim 1～2 is mixed homogeneously with described solid phase powder, 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.

4. method according to claim 3, is characterized in that, the mass ratio of described consolidation liquid and described solid phase powder is (0.5～0.9): 1.

5. a calcium magnesium injectable bone cement of preparing according to the preparation method described in claim 3 or 4.

6. the application of the product as described in any one in claim 1～2 or calcium magnesium injectable bone cement claimed in claim 5, is characterized in that, for the preparation of osseous tissue repair in trauma injectable product.