Injectable collapse-resistant magnesium / calcium phosphate composite bone cement and preparation method thereof

Abstract

The invention discloses injectable collapse-resistant magnesium / calcium phosphate composite bone cement and a preparation method thereof. The bone cement is prepared from solid-phase powder and curing liquid, the solid-phase powder comprises trimagnesium phosphate, calcium phosphate and dipotassium phosphate; the curing liquid is an aqueous solution containing 0.5-2% (w / v) of gelatin and 0-1% (w / v) of citric acid; and mixing the solid-phase powder and the curing liquid to obtain the injectable collapse-resistant magnesium / calcium phosphate composite bone cement. The calcium phosphate and the gelatin are introduced into the magnesium phosphate bone cement, so that the water retention capacity, the collapse resistance and the mechanical property after curing of the blended slurry are improved, the operation safety is improved, and the clinical PVP treatment requirement is met.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to an injectable anti-collapse magnesium phosphate / calcium composite bone cement and a preparation method thereof. Background Art

[0002] Osteoporosis (OP) is a common systemic bone metabolic disease characterized by low bone mass and bone microstructure damage, which can easily lead to non-traumatic fractures. Osteoporotic vertebral compression fractures (OVCFs) are the most common osteoporotic fractures, accounting for about 45% of osteoporotic fractures. Percutaneous vertebroplasty (PVP) is the most commonly used minimally invasive technique for the treatment of OVCFs. Currently, PMMA bone cement is commonly used as a filler in PVP surgery. This bone cement has high mechanical strength, but a large elastic modulus and does not have the biological activity of stimulating osteogenesis. Research reports show that about 8% to 52% of OVCFs patients will suffer from adjacent vertebral compression fractures (AVF) after PVP surgery. Magnesium phosphate bone cement has the characteristics of fast solidification and high initial strength. Studies have shown that a certain concentration of extracellular magnesium ions can promote osteoblast activity and inhibit osteoclast activity. Therefore, magnesium phosphate bone cement has good biological activity and osteogenic ability, and has received widespread attention from researchers. However, the uncontrollable degradation rate, low viscosity, and easy disintegration in water of magnesium phosphate bone cement limit its further application. At the same time, single magnesium phosphate bone cement cannot provide the calcium ions required for bone growth, and its bone-forming ability is limited. Summary of the invention

[0003] Purpose of the invention: The first purpose of the present invention is to provide an injectable anti-disintegration magnesium / calcium composite bone cement to overcome the shortcomings of the existing magnesium phosphate bone cement system; the second purpose of the present invention is to provide a preparation method of the injectable anti-disintegration magnesium / calcium composite bone cement.

[0004] Technical solution: The injectable anti-collapse magnesium phosphate / calcium composite bone cement described in the present invention includes solid phase powder and solidifying liquid; the solid phase powder includes trimagnesium phosphate, calcium phosphate and dipotassium hydrogen phosphate; the solidifying liquid is an aqueous solution containing gelatin at a concentration of 0.5-2% (w / v) and citric acid at a concentration of 0-1% (w / v).

[0005] Preferably, the solid-to-liquid ratio of the solid phase powder to the solidified liquid is 2 to 5 g / mL.

[0006] Preferably, the solid phase powder comprises, by weight: 30 to 80 parts of trimagnesium phosphate, 10 to 40 parts of calcium phosphate, and 10 to 45 parts of dipotassium hydrogen phosphate.

[0007] Preferably, the calcium phosphate salt is α-tricalcium phosphate or monocalcium phosphate.

[0008] The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement of the present invention comprises the following steps:

[0009] (1) mixing trimagnesium phosphate, calcium phosphate and dipotassium hydrogen phosphate to obtain a solid phase powder;

[0010] (2) preparing an aqueous solution having a gelatin concentration of 0.5 to 2% (w / v) and a citric acid concentration of 0 to 1% (w / v) as a bone cement curing liquid;

[0011] (3) Mixing the solid phase powder and the solidifying liquid to obtain the injectable anti-collapse magnesium phosphate / calcium composite bone cement.

[0012] Preferably, in step (1), the mixing is performed by crushing and mixing using a crusher in a dry environment.

[0013] Preferably, in step (2), the aqueous solution is prepared by heating and dissolving at 45-60° C., assisted by mechanical stirring or magnetic stirring.

[0014] Preferably, the preparation method of trimagnesium phosphate comprises the following steps:

[0015] (1) Mix magnesium hydrogen phosphate trihydrate and magnesium hydroxide at a molar ratio of 2:1 and grind;

[0016] (2) The material ground in step (1) is calcined in a furnace at 1150-1400° C. for 2-5 hours, and then ground again after cooling to obtain trimagnesium phosphate powder with a particle size of 1-10 μm.

[0017] Preferably, in step (1), the grinding is: mixing magnesium hydrogen phosphate trihydrate and magnesium hydroxide in an ethanol medium by ball milling at 300-400 rpm for 2-4 hours, and drying at 60-100°C.

[0018] Preferably, in step (2), the grinding is: ball milling the sintered cake in an ethanol medium at 300-400 rpm for 4-18 hours, and drying at 60-100°C.

[0019] Mechanism of the invention: The bone cement of the present invention is a composite of self-curing calcium phosphate salt and magnesium phosphate bone cement, with gelatin solution or gelatin and citric acid solution as the curing liquid. During the curing process, the excellent water retention capacity of gelatin improves the initial fluidity and anti-collapse property of the prepared slurry. As the anhydrous dipotassium hydrogen phosphate powder absorbs water to form a gel, the prepared slurry further has high viscosity and fluidity, and then forms potassium magnesium phosphate hexahydrate with trimagnesium phosphate during the hydration process, and finally solidifies. Calcium phosphate salt has self-curing ability, and hydrates to form calcium-deficient hydroxyapatite or calcium hydrogen phosphate, which has high mechanical strength and osteoconductivity. It releases calcium ions during degradation to promote new bone formation. The bone cement provided by the present invention has good surgical safety and osteogenic ability to meet the clinical PVP treatment needs.

[0020] The innovation of the present invention lies not only in using gelatin solution as a solidifying liquid to improve the anti-collapse property of bone cement, but also in introducing self-solidifying calcium phosphate salt into magnesium phosphate bone cement, so that it can simultaneously participate in the hydration process to form a continuous calcium phosphate phase, which helps to improve the anti-collapse property of the mixed slurry and enhance the mechanical properties after solidification. At the same time, the calcium salt provides bone conductivity.

[0021] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) By introducing calcium phosphate and gelatin into magnesium phosphate bone cement, the water retention capacity, anti-collapse property and mechanical properties after curing of the mixed slurry are improved, the surgical safety is improved to meet the clinical PVP treatment needs; (2) The preparation method of the present invention is simple, the raw materials used are simple, suitable for mass production, and has broad clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a graph showing the anti-collapse property of the magnesium phosphate / calcium composite bone cement prepared in Example 1 of the present invention;

[0023] Figure 2 This is a compressive strength curve of the magnesium phosphate / calcium composite bone cement prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further described below in conjunction with embodiments.

[0025] Example 1

[0026] The preparation method of the injectable anti-collapse magnesium phosphate / calcium composite bone cement of the present invention comprises the following steps:

[0027] (1) 120 g of magnesium hydrogen phosphate trihydrate and 20 g of magnesium hydroxide were mixed in an ethanol medium at 300 rpm for 4 h, and dried at 60° C. The mixed powder was calcined in a muffle furnace at 1150° C. for 5 h, and the product was ball-milled in an ethanol medium at 400 rpm for 18 h, and dried at 60° C. to obtain trimagnesium phosphate powder with a particle size of 1 to 10 μm;

[0028] (2) 45 parts (by weight) of the above-mentioned trimagnesium phosphate, 10 parts of α-tricalcium phosphate, and 45 parts of anhydrous dipotassium hydrogen phosphate were crushed and mixed using a crusher in a dry environment to prepare a bone cement solid phase powder;

[0029] (3) heating and dissolving at 45° C., with the aid of magnetic stirring, to prepare a gelatin aqueous solution with a gelatin concentration of 0.5% (w / v) as a bone cement curing liquid;

[0030] The bone cement solid phase powder and the bone cement solidifying liquid are blended at a solid-liquid ratio of 4 g / mL to obtain magnesium phosphate / calcium composite bone cement.

[0031] Depend on Figure 2 The anti-collapse graph of the magnesium phosphate / calcium composite bone cement prepared in Example 1 of the present invention shows that the mixed slurry does not collapse when injected into deionized water.

[0032] The bone cement prepared in Example 1 has an injectability of 95% and an average compressive strength of 27 MPa.

[0033] Example 2

[0034] The preparation method of the injectable anti-collapse magnesium phosphate / calcium composite bone cement of the present invention comprises the following steps:

[0035] (1) The preparation of trimagnesium phosphate is the same as in Example 1;

[0036] (2) 60 parts of trimagnesium phosphate, 10 parts of α-tricalcium phosphate, and 30 parts of anhydrous dipotassium hydrogen phosphate prepared in Example 1 were crushed and mixed using a crusher in a dry environment to prepare a bone cement solid phase powder;

[0037] (3) Heat to 45°C to dissolve, and stir with magnetic force to prepare a gelatin aqueous solution with a gelatin concentration of 1% (w / v) as the bone cement curing liquid.

[0038] The bone cement solid phase powder and the bone cement solidifying liquid are blended at a solid-liquid ratio of 4 g / mL to obtain magnesium phosphate / calcium composite bone cement.

[0039] The injectability of Example 2 is 99%, and the average compressive strength is 34 MPa.

[0040] Example 3

[0041] The preparation method of the injectable anti-collapse magnesium phosphate / calcium composite bone cement of the present invention comprises the following steps:

[0042] (1) The preparation of trimagnesium phosphate is the same as in Example 1;

[0043] (2) 60 parts of trimagnesium phosphate, 10 parts of monocalcium phosphate, and 30 parts of anhydrous dipotassium hydrogen phosphate prepared in Example 1 were crushed and mixed using a crusher in a dry environment to prepare a bone cement solid phase powder;

[0044] (3) Heat and dissolve at 45°C, and stir with magnetic force to prepare an aqueous solution with a gelatin concentration of 1% (w / v) and a citric acid concentration of 1% (w / v) as a bone cement solidifying solution. The bone cement solid phase powder and the bone cement solidifying solution are blended at a solid-liquid ratio of 4 g / mL to obtain a magnesium phosphate / calcium composite bone cement.

[0045] The injectability of Example 3 is 99%, and the average compressive strength is 37 MPa.

Claims

1. An injectable anti-disintegration magnesium phosphate / calcium composite bone cement, characterized in that: It comprises solid phase powder and solidifying liquid; the solid phase powder comprises trimagnesium phosphate, calcium phosphate and dipotassium hydrogen phosphate; the solidifying liquid is an aqueous solution containing gelatin at a concentration of 0.5-2% (w / v) and citric acid at a concentration of 0-1% (w / v).

2. The injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 1, characterized in that: The solid-to-liquid ratio of the solid phase powder to the solidified liquid is 2-5 g / mL.

3. The injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 1, characterized in that: The solid phase powder comprises, by weight: 30 to 80 parts of trimagnesium phosphate, 10 to 40 parts of calcium phosphate, and 10 to 45 parts of dipotassium hydrogen phosphate.

4. The injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 1, characterized in that: The calcium phosphate salt is α-tricalcium phosphate or monocalcium phosphate.

5. A method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to any one of claims 1 to 4, characterized in that: The following steps are involved: (1) mixing trimagnesium phosphate, calcium phosphate and dipotassium hydrogen phosphate to obtain a solid phase powder; (2) preparing an aqueous solution having a gelatin concentration of 0.5 to 2% (w / v) and a citric acid concentration of 0 to 1% (w / v) as a bone cement curing liquid; (3) Mixing the solid phase powder and the solidifying liquid to obtain the injectable anti-collapse magnesium phosphate / calcium composite bone cement.

6. The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 5, characterized in that: In step (1), the mixing is performed by crushing and mixing using a crusher in a dry environment.

7. The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 5, characterized in that: In step (2), the aqueous solution is prepared by heating and dissolving at 45-60° C., assisted by mechanical stirring or magnetic stirring.

8. The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 5, characterized in that: The preparation method of trimagnesium phosphate comprises the following steps: (1) Mix magnesium hydrogen phosphate trihydrate and magnesium hydroxide at a molar ratio of 2:1 and grind; (2) The material ground in step (1) is calcined in a furnace at 1150-1400° C. for 2-5 hours, and then ground again after cooling to obtain trimagnesium phosphate powder with a particle size of 1-10 μm.

9. The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 8, characterized in that: In step (1), the grinding is as follows: magnesium hydrogen phosphate trihydrate and magnesium hydroxide are mixed by ball milling at 300-400 rpm in an ethanol medium for 2-4 hours, and then dried at 60-100°C.

10. The method for preparing the injectable anti-collapse magnesium phosphate / calcium composite bone cement according to claim 8, characterized in that: In step (2), the grinding is as follows: the sintered cake is ball-milled in an ethanol medium at 300-400 rpm for 4-18 hours, and then dried at 60-100°C.

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