Calcium sulfate composite bone cement and preparation method thereof

Abstract

The invention discloses calcium sulfate composite bone cement and a preparation method thereof, the bone cement comprises powder and liquid, the powder is composed of 60-98% by mass of alpha-calcium sulfate hemihydrate and 2-40% by mass of metal powder, the liquid is water or 0.01-2.5% by mass of a sodium carboxymethyl cellulose solution, and the mass ratio of the powder to the liquid is 2: 1. The invention discloses a preparation method of calcium sulfate composite bone cement. Calcium sulfate hemihydrate is prepared by using a new method, and metal elements necessary for a human body are compounded in a prepared calcium sulfate matrix to endow the material with a novel bone induction function, for example, the added metal zinc powder is widely distributed in most tissues of the human body, but is highly specifically distributed in bone tissues, so that the bone induction function of the material is enhanced. According to the present invention, it has been proved that the polypeptide has a direct and specific proliferation effect on osteoblasts, and can stimulate bone formation and mineralization by directly activating methionine-tRNA synthetase in osteoblasts, inhibit the activity of osteoclasts, and maintain the dynamic balance of bone metabolism.

Description

Technical Field

[0001] The present invention relates to bone cement and a preparation method thereof, in particular to a calcium sulfate composite bone cement and a preparation method thereof. Background Art

[0002] Calcium sulfate has become a very important medical bone repair implant material because it has many characteristics of ideal bone replacement materials, including biocompatibility, degradability, injectability, osteoconductivity and certain mechanical strength. It can be used in the surgery and treatment of diseases such as fractures, bone defects and bone tumors.

[0003] Calcium sulfate can be divided into calcium sulfate dihydrate, calcium sulfate hemihydrate, and calcium sulfate anhydrous based on its molecular structure and the amount of crystalline water it contains. Calcium sulfate hemihydrate can be further divided into α-calcium sulfate hemihydrate and β-calcium sulfate hemihydrate based on the dehydration temperature and system environment. The preparation and performance research of α-calcium sulfate hemihydrate (α-CSH) is crucial for the application and development of artificial bone implant materials.

[0004] Currently, commonly used methods for preparing α-CSH include autoclaving, hydrothermal processing, and atmospheric pressure saline solution processing. Autoclaving, hydrothermal processing, and other commonly used methods have high production costs and energy consumption, which limits their industrial application. While the atmospheric pressure saline solution method significantly reduces production costs, it typically has a high saline concentration, making desalination difficult and, therefore, has not yet been widely adopted.

[0005] In addition, studies have shown that calcium sulfate, as a traditional bone repair material, only has osteoconductivity and does not have osteoinduction itself. It mainly provides physical support for the creeping replacement of new bone tissue by constructing a three-dimensional porous scaffold. Its osteoinductivity and antibacterial properties need to be further enhanced. Summary of the Invention

[0006] In order to solve the shortcomings of the above technology, the present invention provides a calcium sulfate composite bone cement and a preparation method thereof.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is: a calcium sulfate composite bone cement, including powder and liquid, wherein the powder is composed of 60-98% by mass of α-calcium sulfate hemihydrate and 2-40% by mass of metal powder, and the liquid is water or a sodium carboxymethyl cellulose solution with a mass fraction of 0.01-2.5%, and the mass ratio of powder to liquid is 2:1.

[0008] Preferably, the metal powder is any one of zinc powder, iron powder, copper powder, manganese powder, cobalt powder and molybdenum powder, or alloy powder of several of them.

[0009] Preferably, the metal powder is zinc powder or iron powder or alloy powder thereof, wherein the mass ratio of zinc to iron in the alloy powder is 1 to 5:1.

[0010] Preferably, the metal powder is zinc powder, and its content accounts for 2-30% of the total powder amount.

[0011] Preferably, the metal powder is iron powder, and its content accounts for 3.5-22% of the total powder.

[0012] Preferably, the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50 μm, the particle size distribution range of the metal powder is 0.5-74 μm, and the purity thereof is ≥99.5%.

[0013] Preferably, the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-20 μm, and the particle size distribution range of the metal powder is 0.5-35 μm.

[0014] Preferably, the liquid is a 0.5-1.5% sodium carboxymethylcellulose solution.

[0015] A method for preparing calcium sulfate composite bone cement comprises the following steps: Step S1, adding a certain amount of water into a container, setting the container rotation speed to 180-220 r / min, setting the heating temperature to 100-115°C, and continuing stirring and heating until the reaction is completed and the water occupies 30-60% of the container volume; Step S2: adding weighed succinic acid and calcium chloride to the container in sequence, dissolving, mixing and stirring to obtain a transparent solution; Step S3: Sodium sulfate is added to the transparent solution, and the transparent solution becomes a milky white suspension; Step S4: When the temperature of the milky white suspension reaches 95-105°C, start timing and react for 4-6 hours; Step S5, the reaction product is quickly filtered, and rinsed with water ≥95°C for 3 times, and then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven at 110°C for 12-24 hours to obtain α-calcium sulfate hemihydrate; Step S6, weighing the prepared 60-98% calcium sulfate hemihydrate and 2-40% metal powder according to a ratio, and mixing them for 3-6 hours to obtain bone cement powder; Step S7, dissolving sodium carboxymethyl cellulose in water to obtain a 0.01-2.5% sodium carboxymethyl cellulose solution; Step S8: Mix the bone cement powder and liquid in a mass ratio of 2:1, stir and mix, and obtain calcium sulfate composite bone cement containing metal powder after solidification.

[0016] Preferably, in step S2, the mass ratio of succinic acid to water is 0.001-0.01, and the mass ratio of calcium chloride to water is 0.15-0.25; in step S3, the mass ratio of sodium sulfate to water is 0.05-0.15.

[0017] Compared with the prior art, the present invention has the following beneficial effects: (1) Compared with the normal pressure salt solution method, the preparation of calcium sulfate hemihydrate uses soluble calcium chloride instead of water-insoluble calcium sulfate dihydrate as raw material, eliminating the requirements for the morphology, particle size and other parameters of the initial calcium sulfate dihydrate in the preparation process of calcium sulfate hemihydrate. It starts with a transparent solution, improves the reaction efficiency, and the reaction system is stable, which is conducive to the industrial production control of the process. α-calcium sulfate hemihydrate is prepared by the reaction raw material (calcium chloride) itself and high-temperature catalytic crystallization, and calcium chloride and sodium sulfate react and crystallize. (2) The prepared calcium sulfate hemihydrate is compounded with metal powder to prepare inorganic / metal composite bone cement. The addition of metal powder changes the color of calcium sulfate bone cement. For example, when zinc powder is added, it changes from white to gray, and when iron powder is added, it changes from white to brown-black. This makes it have a color difference with bone tissue and is used to distinguish the interface between bone and bone cement, which is beneficial for clinical operation and application. (3) During the hydration and solidification process of calcium sulfate, the metal powder is evenly dispersed in the calcium sulfate, acting as a reinforcing phase to increase the mechanical properties of the bone cement. At the same time, the zinc powder or iron powder reacts with water to generate zinc oxide or ferric hydroxide (or ferric oxide). The continuously released zinc ions or iron ions, after contacting bacteria, damage the bacterial cell membrane and interfere with bacterial metabolism, thus giving the metal powder-containing calcium sulfate bone cement certain antibacterial properties, increasing the porosity of the bone cement, and enhancing the bone inductivity of the bone cement. (4) The bone cement curing process only releases a slight amount of heat, and the unreacted metal iron powder is evenly dispersed in the calcium sulfate solid body. Under the action of the alternating magnetic field, the bone cement is heated by hysteresis, making the temperature of the calcium sulfate bone cement higher than 42°C, which kills or eliminates tumor cells and sterilizes them at high temperature. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the XRD pattern of calcium sulfate hemihydrate prepared in Example 1 of the present invention.

[0019] Figure 2 This is a compression performance diagram of the zinc-calcium sulfate composite bone cement prepared in Examples 1-4 of the present invention.

[0020] Figure 3 This is an SEM image of the zinc-calcium sulfate composite bone cement prepared in Example 2 of the present invention.

[0021] Figure 4 This is the XRD pattern of the zinc-calcium sulfate composite bone cement prepared in Example 3 of the present invention after curing.

[0022] Figure 5 This is a compression performance diagram of the iron-containing calcium sulfate composite bone cement prepared in Examples 5-8 of the present invention.

[0023] Figure 6 This is a magnetocaloric performance diagram of the calcium sulfate composite bone cement prepared in Example 7 of the present invention.

[0024] Figure 7 This is a magnetocaloric performance diagram of the calcium sulfate composite bone cement prepared in Example 9 of the present invention.

[0025] Figure 8 This is a simulated degradation curve of the calcium sulfate composite bone cement prepared in Example 10 of this invention.

[0026] Figure 9 This is a mechanical test curve diagram of the calcium sulfate composite bone cement prepared in Example 11 of the present invention. DETAILED DESCRIPTION

[0027] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0028] The bone cement of the present invention is mainly composed of calcium sulfate and metal powder. The calcium sulfate / metal powder bone cement has the advantages of high mechanical strength and degradable absorption. At the same time, zinc powder and the like undergo an oxidation reaction in an aqueous environment to produce partial zinc oxide, which has certain antibacterial properties. At the same time, a new method is used to prepare α-calcium sulfate hemihydrate, which overcomes the shortcomings of the existing technology. Excess soluble calcium chloride is used instead of water-insoluble calcium sulfate dihydrate as a raw material. Calcium chloride serves as both a reaction raw material and a crystal-transforming agent. The added calcium chloride first reacts with sodium sulfate to produce calcium sulfate dihydrate, reducing the concentration of the calcium chloride salt solution. The excess calcium chloride acts as a crystal-transforming agent, converting the prepared calcium sulfate dihydrate into calcium sulfate hemihydrate. Excess calcium chloride and other salts are removed through high-temperature water rinsing and ethanol rinsing processes to obtain pure calcium sulfate hemihydrate powder (as can be seen from the XRD pattern of Example 1, the powder contains only calcium sulfate hemihydrate). The desalination efficiency is high and the cost is reduced.

[0029] Example 1

[0030] A zinc-calcium sulfate composite bone cement, the powder is composed of 70% calcium sulfate hemihydrate and 30% zinc powder, and the liquid is a 2.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm, the particle size distribution range of zinc powder is 0.5-74μm, and the purity is ≥99.5%; A preparation method of zinc-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water to a container (e.g., a reactor), set the container speed to 180 r / min, set the heating temperature to 115°C, and continue stirring and heating until the reaction is complete and the water occupies 60% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.01, and the mass ratio of calcium chloride to water is 0.25; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.15; (4) When the temperature of the milky white suspension reaches 105°C, start timing and react for 6 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 12 h to obtain α-calcium sulfate hemihydrate.

[0031] (6) Weigh 70% of the prepared calcium sulfate hemihydrate and 30% of zinc powder according to the ratio, mix them for 6 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 2.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-containing calcium sulfate bone cement.

[0032] The prepared calcium sulfate hemihydrate was characterized by XRD. Figure 1 As shown, the prepared calcium sulfate hemihydrate is α-calcium sulfate hemihydrate.

[0033] The zinc-calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 2 As shown in the figure, the compressive strength of zinc-calcium sulfate bone cement is 18.12±2.82MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0034] Example 2

[0035] A zinc-calcium sulfate composite bone cement, the powder is composed of 90% calcium sulfate hemihydrate and 10% zinc powder, and the liquid is a 0.01% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-20μm, the particle size distribution range of zinc powder is 0.5-74μm, and the purity is ≥99.5%; A preparation method of zinc-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water into the container, set the container speed to 190 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume;

[0036] (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.001, and the mass ratio of calcium chloride to water is 0.15; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.05; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 5 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0037] (6) Weigh 90% of the prepared calcium sulfate hemihydrate and 10% of zinc powder according to the ratio, mix them for 5 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 0.01% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-containing calcium sulfate bone cement.

[0038] The prepared zinc-calcium sulfate composite bone cement was ground into powder after solidification and subjected to SEM characterization analysis. Figure 3 As shown in the figure, the morphology of the zinc-calcium sulfate composite bone cement after curing is a lamellar block structure.

[0039] The zinc-calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 2 As shown in the figure, the compressive strength of zinc-calcium sulfate composite bone cement is 14.28±1.88MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0040] Example 3

[0041] A zinc-calcium sulfate composite bone cement, the powder is composed of 94% calcium sulfate hemihydrate and 6% zinc powder, and the liquid is a 0.12% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm, the particle size distribution range of zinc powder is 0.5-35μm, and the purity is ≥99.5%; A preparation method of zinc-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water into the container, set the container speed to 180 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.01, and the mass ratio of calcium chloride to water is 0.25; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.1; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 5 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0042] (6) Weigh the prepared 94% calcium sulfate hemihydrate and 6% zinc powder according to the ratio, mix them for 4 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 0.12% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-calcium sulfate composite bone cement.

[0043] The cured zinc-calcium sulfate composite bone cement was characterized by XRD. Figure 4 As shown, the components of the cured zinc-calcium sulfate composite bone cement are calcium sulfate dihydrate, zinc oxide, and unreacted zinc metal.

[0044] The zinc-calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 2 As shown in the figure, the compressive strength of zinc-calcium sulfate composite bone cement is 16.46±1.49MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0045] Example 4

[0046] A zinc-calcium sulfate composite bone cement, the powder is composed of 98% calcium sulfate hemihydrate and 2% zinc powder, and the liquid is a 1.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm; the particle size distribution range of zinc powder is 0.5-74μm, and the purity is ≥99.5%; A preparation method of zinc-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water into the container, set the container speed to 200 r / min, set the heating temperature to 115 °C, continue stirring and heating until the reaction is completed and the water occupies 40% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.006, and the mass ratio of calcium chloride to water is 0.22; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.09; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 4 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0047] (6) Weigh the prepared 98% calcium sulfate hemihydrate and 2% zinc powder according to the ratio, mix them for 3 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 1.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-calcium sulfate composite bone cement.

[0048] The zinc-calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 2 As shown in the figure, the compressive strength of zinc-calcium sulfate composite bone cement is 17.97±1.46MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0049] Example 5

[0050] An iron-containing calcium sulfate composite bone cement, the powder is composed of 78% calcium sulfate hemihydrate and 22% iron powder, and the liquid is a 0.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm; the particle size distribution range of iron powder is 0.5-74μm, and the purity is ≥99.5%; A preparation method of iron-containing calcium sulfate composite bone cement is: (1) Add a certain amount of water into the container, set the container speed to 180 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.2; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.1; (4) When the temperature of the milky white suspension reaches 95°C, start timing and react for 5 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0051] (6) Weigh the prepared 78% calcium sulfate hemihydrate and 22% iron powder according to the ratio, mix them for 6 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 0.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain iron-containing calcium sulfate composite bone cement.

[0052] The iron-containing calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 5 As shown in the figure, the compressive strength of the iron-calcium sulfate composite bone cement is 17.43±2.33MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0053] Example 6

[0054] An iron-containing calcium sulfate composite bone cement, the powder is composed of 90% calcium sulfate hemihydrate and 10% iron powder, and the liquid is a 0.8% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-20μm; the particle size distribution range of iron powder is 0.5-35μm, and the purity is ≥99.5%; A preparation method of iron-containing calcium sulfate composite bone cement is: (1) Add a certain amount of water into the container, set the container speed to 190 r / min, set the heating temperature to 115 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.006, and the mass ratio of calcium chloride to water is 0.22; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.12; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 5 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 18 h to obtain α-calcium sulfate hemihydrate.

[0055] (6) Weigh 90% of the prepared calcium sulfate hemihydrate and 10% of the iron powder according to the ratio, mix them for 3 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 0.8% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain iron-containing calcium sulfate composite bone cement.

[0056] The iron-containing calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 5 As shown in the figure, the compressive strength of the iron-calcium sulfate composite bone cement is 13.21±2.02MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0057] Example 7

[0058] An iron-containing calcium sulfate composite bone cement, the powder is composed of 92.5% calcium sulfate hemihydrate and 7.5% iron powder, and the liquid is a 1.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm; the particle size distribution range of iron powder is 0.5-35μm, and the purity is ≥99.5%; A preparation method of iron-containing calcium sulfate composite bone cement is: (1) Add a certain amount of water into the container, set the container speed to 220 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.25; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.14; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 5 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 12 h to obtain α-calcium sulfate hemihydrate.

[0059] (6) Weigh the prepared 92.5% calcium sulfate hemihydrate and 7.5% iron powder according to the ratio, mix them for 3 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 1.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain iron-containing calcium sulfate composite bone cement.

[0060] The iron-containing calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 5 As shown in the figure, the compressive strength of the iron-calcium sulfate composite bone cement is 14.87±4.24 MPa, which meets the requirement of 1~10 MPa for the compressive strength of human cancellous bone.

[0061] The solidified iron-containing calcium sulfate composite bone cement was subjected to magnetothermal test under an alternating magnetic field. Figure 6 As shown, under the heating of the alternating magnetic field, the temperature of the iron-containing bone cement reaches 47.9°C in 2 minutes, which meets the requirement that the bone cement temperature is higher than 42°C, thereby killing or eliminating tumor cells and achieving high-temperature sterilization.

[0062] Example 8

[0063] An iron-containing calcium sulfate composite bone cement, the powder is composed of 96.5% calcium sulfate hemihydrate and 3.5% iron powder, and the liquid is a 0.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid mass ratio of 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-20μm; the particle size distribution range of iron powder is 0.5-35μm, and the purity is ≥99.5%; A preparation method of iron-containing calcium sulfate composite bone cement is: (1) Add a certain amount of water into the container, set the container speed to 180 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.2; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.08; (4) When the temperature of the milky white suspension reaches 100°C, start timing and allow the reaction to continue for 6 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 16 h to obtain α-calcium sulfate hemihydrate.

[0064] (6) Weigh the prepared 96.5% calcium sulfate hemihydrate and 3.5% iron powder according to the ratio, mix them for 3 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 1.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain iron-containing calcium sulfate composite bone cement.

[0065] The iron-containing calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 5 As shown in the figure, the compressive strength of the iron-calcium sulfate composite bone cement is 15.41±1.15MPa, which meets the requirement of 1~10MPa compressive strength of human cancellous bone.

[0066] Example 9

[0067] A zinc-iron-calcium sulfate composite bone cement, comprising a powder composed of 76% calcium sulfate hemihydrate and 24% zinc-iron alloy powder, and a liquid consisting of a 1% sodium carboxymethyl cellulose solution, with a powder-to-liquid ratio of 2:1. The α-calcium sulfate hemihydrate particle size distribution range is 0.5-20 μm, the zinc powder particle size distribution range is 0.5-35 μm, and the purity is ≥99.5%. The zinc-iron alloy powder has a mass ratio of 2:1.

[0068] A preparation method of zinc-iron-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water into the container, set the container speed to 220 r / min, set the heating temperature to 100 °C, continue stirring and heating until the reaction is completed and the water occupies 30% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.2; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.10; (4) When the temperature of the milky white suspension reaches 95°C, start timing and react for 6 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0069] (6) Weigh the prepared 76% calcium sulfate hemihydrate and 24% zinc-iron alloy powder according to the ratio, mix them for 4 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 1% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-iron-calcium sulfate composite bone cement.

[0070] The cured zinc-iron-calcium sulfate composite bone cement was subjected to magnetothermal testing under an alternating magnetic field. Figure 7 As shown, under the heating of the alternating magnetic field, the temperature of the zinc-iron bone cement reaches 74.3°C in 2 minutes, which meets the requirement that the bone cement temperature is higher than 42°C, kills or eliminates tumor cells, and has the effect of high-temperature sterilization.

[0071] Example 10

[0072] A zinc-iron-calcium sulfate composite bone cement, comprising a powder composed of 60% calcium sulfate hemihydrate and 40% zinc-iron alloy powder, and a liquid consisting of a 1.5% sodium carboxymethyl cellulose solution, with a powder-to-liquid ratio of 2:1. The particle size distribution of α-calcium sulfate hemihydrate is 0.5-50 μm, the particle size distribution of zinc-iron powder is 0.5-35 μm, and the purity is ≥99.5%. The mass ratio of the zinc-iron alloy powder is 5:1.

[0073] A preparation method of zinc-iron-calcium sulfate composite bone cement is as follows: (1) Add a certain amount of water into the container, set the container speed to 180 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.22; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.10; (4) When the temperature of the milky white suspension reaches 95°C, start timing and react for 6 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0074] (6) Weigh the prepared 60% calcium sulfate hemihydrate and 40% zinc-iron alloy powder according to the ratio, mix them for 4 hours and obtain bone cement powder; (7) Dissolve sodium carboxymethyl cellulose in water to obtain a 0.5% sodium carboxymethyl cellulose solution; (8) Bone cement powder and liquid are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain zinc-iron-calcium sulfate composite bone cement.

[0075] The samples were prepared into blocks and subjected to a simulated degradation test in a phosphate buffer solution at 37°C with a liquid-to-solid ratio of 100:1. The phosphate buffer solution was replaced every 7 days. Figure 8 As shown in the figure, the cumulative mass loss of zinc-iron-calcium sulfate composite bone cement was 68.32% at 91 days.

[0076] Example 11

[0077] A copper-calcium sulfate composite bone cement, the powder is composed of 89% calcium sulfate hemihydrate and 11% copper powder, the liquid is water, and the mass ratio of powder to liquid is 2:1; the particle size distribution range of α-calcium sulfate hemihydrate is 0.5-50μm, the particle size range of copper powder is 0.5-74μm, and the purity is ≥99.5%; A preparation method of copper-containing calcium sulfate composite bone cement is: (1) Add a certain amount of water into the container, set the container speed to 180 r / min, set the heating temperature to 110 °C, continue stirring and heating until the reaction is completed and the water occupies 50% of the container volume; (2) Weigh succinic acid and calcium chloride in sequence, dissolve, mix and stir to obtain a transparent solution; the mass ratio of succinic acid to water is 0.005, and the mass ratio of calcium chloride to water is 0.25; (3) Sodium sulfate is then added to the transparent solution, and the transparent solution becomes a milky white suspension; the mass ratio of sodium sulfate to water is 0.15; (4) When the temperature of the milky white suspension reaches 95°C, start timing and react for 6 hours; (5) The reaction product was quickly filtered and rinsed with water ≥95°C for 3 times, then rinsed with anhydrous ethanol for 1 time, and then transferred to an oven and dried at 110°C for 24 hours to obtain α-calcium sulfate hemihydrate.

[0078] (6) Weigh the prepared 89% calcium sulfate hemihydrate and 11% copper powder according to the ratio, mix them for 6 hours and obtain bone cement powder; (7) Bone cement powder and water are mixed together in a mass ratio of 2:1, stirred, and solidified to obtain copper-containing calcium sulfate composite bone cement.

[0079] The copper-calcium sulfate composite bone cement was made into a Φ6mm×12mm cylinder and the compression performance test was carried out. Figure 9 The figure shows the mechanical test curve of the bone cement prepared in Example 11. According to the method of calculating the compressive strength by load / compression area, the compressive strength of the copper-calcium sulfate composite bone cement is calculated to be 14.85±2.37 MPa, which meets the requirement of 1-10 MPa compressive strength of human cancellous bone.

[0080] This invention uses a novel method to prepare calcium sulfate hemihydrate. Essential metal elements for the human body are compounded into the prepared calcium sulfate matrix to impart novel osteoinductive properties to the material. For example, the added metallic zinc powder is widely distributed in most tissues of the human body, but exhibits a highly specific distribution in bone tissue. It has been shown to have a direct and specific proliferative effect on osteoblasts. It can stimulate bone formation and mineralization by directly activating methionyl-tRNA synthetase in osteoblasts, while inhibiting osteoclast activity and maintaining bone metabolism homeostasis. Furthermore, the sustained release of zinc ions, upon contact with bacteria, also exhibits a certain degree of antibacterial properties by damaging bacterial cell membranes and interfering with bacterial metabolism.

[0081] The above embodiments are not limitations of the present invention, and the present invention is not limited to the above examples. Any changes, modifications, additions or substitutions made by technicians in this technical field within the scope of the technical solution of the present invention also fall within the scope of protection of the present invention.

Claims

1. A calcium sulfate composite bone cement comprising powder and liquid, characterized in that: The powder is composed of 60-98% by mass of α-calcium sulfate hemihydrate and 2-40% by mass of metal powder. The liquid is water or a sodium carboxymethyl cellulose solution with a mass fraction of 0.01-2.5%. The mass ratio of the powder to the liquid is 2:

1.

2. The calcium sulfate composite bone cement according to claim 1, wherein: The metal powder is any one of zinc powder, iron powder, copper powder, manganese powder, cobalt powder and molybdenum powder, or alloy powder of several of them.

3. The calcium sulfate composite bone cement according to claim 2, wherein: The metal powder is zinc powder or iron powder or alloy powder thereof.

4. The calcium sulfate composite bone cement according to claim 3, wherein: The metal powder is zinc powder, and its content accounts for 2-30% of the total powder amount.

5. The calcium sulfate composite bone cement according to claim 3, wherein: The metal powder is iron powder, and its content accounts for 3.5-22% of the total powder amount.

6. The calcium sulfate composite bone cement according to claim 1, wherein: The particle size distribution range of the α-calcium sulfate hemihydrate is 0.5-50 μm, the particle size distribution range of the metal powder is 0.5-74 μm, and the purity thereof is ≥99.5%.

7. The calcium sulfate composite bone cement according to claim 6, characterized in that: The particle size distribution range of the α-calcium sulfate hemihydrate is 0.5-20 μm, and the particle size distribution range of the metal powder is 0.5-35 μm.

8. The calcium sulfate composite bone cement according to claim 1, wherein: The liquid is a 0.5-1.5% sodium carboxymethyl cellulose solution.

9. A method for preparing a calcium sulfate composite bone cement according to any one of claims 1 to 8, characterized in that: The following steps are involved: Step S1, adding a certain amount of water into a container, setting the container rotation speed to 180-220 r / min, setting the heating temperature to 100-115°C, and continuing stirring and heating until the reaction is completed and the water occupies 30-60% of the container volume; Step S2: adding weighed succinic acid and calcium chloride to the container in sequence, dissolving, mixing and stirring to obtain a transparent solution; Step S3: Sodium sulfate is added to the transparent solution, and the transparent solution becomes a milky white suspension; Step S4: When the temperature of the milky white suspension reaches 95-105°C, start timing and react for 4-6 hours; Step S5, the reaction product was quickly filtered, and washed with water ≥95°C for 3 times, and then washed with anhydrous ethanol for 1 time, and then transferred to an oven at 110°C for 12-24 hours to obtain α-calcium sulfate hemihydrate; Step S6, weighing the prepared 60-98% calcium sulfate hemihydrate and 2-40% metal powder according to a ratio, and mixing them for 3-6 hours to obtain bone cement powder; Step S7, dissolving sodium carboxymethyl cellulose in water to obtain a 0.01-2.5% sodium carboxymethyl cellulose solution; Step S8: Mix the bone cement powder and liquid in a mass ratio of 2:1, stir and mix, and obtain calcium sulfate composite bone cement containing metal powder after solidification.

10. The method for preparing calcium sulfate composite bone cement according to claim 9, wherein: In step S2, the mass ratio of succinic acid to water is 0.001-0.01, and the mass ratio of calcium chloride to water is 0.15-0.25; in step S3, the mass ratio of sodium sulfate to water is 0.05-0.15.

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