A calcium phosphate-based bioceramic with high crystal phase purity and a preparation method thereof

Abstract

The present invention discloses a high-crystalline purity calcium phosphate bioceramic and a preparation method thereof. The method comprises: 1) mixing citric acid, phytic acid, and a portion of a calcium source in water to prepare a main solution; and adding a cross-linking agent to prepare a mixed solution; 2) mixing the remaining calcium source with an esterified dispersant to prepare a calcium pre-dispersant; 3) mixing the calcium pre-dispersant in step 2) and the mixed solution in step 1) with an initiator, reacting to prepare a gel; and 4) calcining the gel in step 3) to prepare the calcium phosphate bioceramic. The method solves the problems of product crystalline phase difference and low purity caused by uneven mixing, and at the same time, replaces ammonium phosphate with phytic acid, avoiding the problems of environmental pollution and wastewater recovery caused by ammonium salts.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and in particular relates to a high-crystalline purity calcium phosphate bioceramic and a preparation method thereof. Background Art

[0002] In the 1980s, American researchers invented a variety of calcium phosphate compositions that can self-fix in body fluids to form hydroxyapatite, which is used in the field of absorbable bone cement materials. Among them, tetracalcium phosphate (Ca4(PO4)2O) is a key component of self-setting calcium phosphate systems. Compared with stable tricalcium phosphate and hydroxyapatite, it has a higher molar calcium content and an unstable crystal structure. In simulated body fluids, it immediately releases calcium ions and reacts with calcium and phosphorus sources to form more stable hydroxyapatite, thereby promoting bone tissue repair.

[0003] Traditionally, tetracalcium phosphate is prepared by solid-phase mixing an excess calcium source with hydroxyapatite followed by high-temperature melting. However, due to drawbacks such as large solid-solid mixing particle size, difficulty in uniform dispersion, and low production efficiency, this leads to an uneven calcium-phosphorus ratio during the melting reaction, resulting in low crystallinity, contamination with other calcium phosphates, and poor batch production stability. Therefore, overcoming the uneven dispersion of materials caused by solid-solid mixing is key to producing high-quality tetracalcium phosphate. Summary of the Invention

[0004] To address the difficulty in preparing high-crystalline purity calcium phosphate bioceramics using a high-temperature solid-phase melting method, the present invention provides a method for preparing high-purity calcium phosphate bioceramics using a sol-gel method. By selecting different sol precursors (such as citric acid, phytic acid, a calcium source, an initiator, or a cross-linking agent), a double network gel is formed through polymerization and esterification reactions, and then calcined to prepare high-crystalline purity calcium phosphate bioceramics, such as at least one of high-crystalline purity tetracalcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate, and hydroxyapatite.

[0005] The technical solutions of the present invention are as follows:

[0006] A method for preparing a calcium phosphate bioceramic, comprising the following steps:

[0007] 1) mixing citric acid, phytic acid, and a portion of a calcium source in water to prepare a main solution; and adding a cross-linking agent to prepare a mixed solution;

[0008] 2) mixing the remaining calcium source with the esterified dispersant to prepare a calcium pre-dispersant;

[0009] 3) mixing the calcium pre-dispersant in step 2), the mixed solution in step 1) and an initiator, and reacting them to prepare a gel;

[0010] 4) calcining the gel in step 3) to prepare the calcium phosphate bioceramic.

[0011] According to the present invention, in step 1), the main solution is acidic; specifically, the pH of the main solution is less than 5, preferably less than 4.2.

[0012] According to the present invention, in step 1), the cross-linking agent is acrylic acid.

[0013] According to the present invention, in step 1), the content of the cross-linking agent is 1 wt% to 25 wt% of the total mass of phytic acid, citric acid and calcium source, preferably 3 wt% to 22 wt%.

[0014] According to the present invention, in step 1) or step 2), the calcium source is selected from at least one of calcium oxide, calcium hydroxide, calcium carbonate, and the like.

[0015] According to the present invention, in step 1), the molar ratio of the total molar amount of phytic acid and citric acid to the part of the calcium source is (0.5-6):1, preferably (0.6-4):1.

[0016] According to the present invention, in step 1), the molar ratio of phytic acid to citric acid is 1:(0.7-8), preferably 1:(1-5).

[0017] In the present invention, phytic acid is a phosphorus source and citric acid is a complexing auxiliary agent.

[0018] In step 1) of the present invention, the amount of water added is not particularly limited, as long as the citric acid, phytic acid and part of the calcium source are uniformly mixed in the water.

[0019] According to the present invention, the molar ratio of the calcium source in step 1) to the calcium source in step 2) is (0.2-1):1, preferably (0.3-0.9):1.

[0020] According to the present invention, in step 2), the esterification dispersant is ethylene glycol.

[0021] According to the present invention, in the calcium pre-dispersant of step 2), the concentration of the calcium source is 10wt% to 55wt%, preferably 15wt% to 50wt%, for example, 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, 35wt%, 40wt%, 45wt% or 50wt%.

[0022] According to the present invention, in step 3), the initiator is dibenzoyl peroxide.

[0023] According to the present invention, in step 3), the mass of the initiator is 0.5 wt% to 9 wt% of the cross-linking agent, preferably 1 wt% to 7.5 wt%.

[0024] According to the present invention, in step 3), the reaction is an esterification reaction and a cross-linking reaction.

[0025] According to the present invention, in step 3), the reaction time is 0.5h to 12h.

[0026] According to the present invention, in step 3), the gel system may be heated and dried before being crushed. Exemplarily, the gel system may be dried at 180° C. for 6 hours.

[0027] According to the present invention, in step 4), the calcination temperature is 900° C. to 1800° C., preferably 1200° C. to 1500° C., illustratively 1200° C., 1300° C., 1400° C., 1450° C. or 1500° C. The calcination time is 2 h to 12 h, preferably 3 h to 8 h.

[0028] According to the present invention, in step 4), the gel may be dried first to obtain a dry gel, which may then be crushed and calcined to uniformly distribute the raw materials.

[0029] As an exemplary embodiment of the present invention, the preparation method of the calcium phosphate bioceramic specifically includes:

[0030] 1) preparing an acid solution of citric acid and phytic acid, adding a portion of a calcium source, and mixing the solution to make it uniform and strongly acidic to prepare a main solution; adding a crosslinking agent to the main solution and stirring to prepare a mixed solution;

[0031] 2) adding the remaining calcium source to the esterified dispersant and dispersing with high-speed stirring to prepare a calcium pre-dispersant;

[0032] 3) adding the calcium pre-dispersant prepared in step 2) to the mixed solution prepared in step 1), stirring the mixture until uniform, and then adding an initiator (e.g., dibenzoyl peroxide) to carry out esterification and cross-linking reactions to form a gel;

[0033] 4) After drying the gel in step 3), the gel is crushed and calcined to produce a calcium phosphate bioceramic.

[0034] The invention uses phytic acid solution as a phosphorus source, citric acid as a complexing auxiliary agent, calcium oxide, calcium hydroxide, calcium carbonate and the like as a calcium source, water as a solvent, ethylene glycol as an esterification dispersant, acrylic acid as a cross-linking agent, and prepares calcium phosphate bioceramics with high crystal phase purity through high-temperature calcination.

[0035] Preferably, the calcium phosphate bioceramic is at least one selected from tetracalcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate and hydroxyapatite.

[0036] The present invention also provides a calcium phosphate bioceramic prepared by the method.

[0037] The present invention also provides applications of the calcium phosphate bioceramics in the fields of orthopedics and dentistry.

[0038] Beneficial effects of the present invention

[0039] The present invention utilizes phytic acid and calcium, citric acid and calcium to react respectively to form a complex in aqueous solution, then by cross-linking agent (such as acrylic acid) through free radical initiated polymerization, and esterification dispersant (such as ethylene glycol) and phytic acid or citric acid esterification to form a double network structure, calcium ions are restricted and evenly dispersed in the gel network, and calcium phosphate bioceramics are obtained through drying, pulverization and high-temperature calcination. The organic matter in the gel is all converted into carbon dioxide and water during high-temperature calcination, which solves the problems such as the crystalline phase difference and purity low of the product brought by uneven mixing, while replacing ammonium phosphate with phytic acid, avoiding the problem of environmental pollution and wastewater recovery brought by ammonium salt. The present invention can be used not only for the preparation of tetracalcium phosphate, but also for high-quality α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) with a calcium-phosphorus molar ratio greater than 1.0. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 4 is the XRD pattern of TTCP obtained in Example 4.

[0041] Figure 2 This is the XRD pattern of β-TCP obtained in Example 5.

[0042] Figure 3 This is the XRD pattern of α-TCP obtained in Example 5.

[0043] Figure 4 This is the XRD pattern of HA obtained in Example 6.

[0044] Figure 5 Be the SEM figure of the TTCP obtained among Example 7. DETAILED DESCRIPTION

[0045] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0046] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0047] Example 1

[0048] Citric acid and phytic acid were weighed, water was added to form a solution, and a portion of calcium hydroxide was added. The solution was homogeneously strongly acidic and used as the main solution. The molar ratio of phytic acid, citric acid and calcium hydroxide, as well as the pH and solution state of the main solution are shown in Table 1. The samples were recorded as samples 1-5.

[0049] Example 2

[0050] Acrylic acid monomer was added to the homogeneous acidic main solution of Example 1 and stirred for 1 hour. The remaining powdered solid calcium source, calcium hydroxide, was then added to a high-concentration ethylene glycol solution and dispersed with high-speed stirring. The solution was then added to the main solution and stirred evenly. Dibenzoyl peroxide was then added and stirred until the esterification and cross-linking reactions were complete to form a gel. The concentration of the cross-linking agent, the concentration of calcium hydroxide in ethylene glycol, and the gel state of the system are shown in Table 2. Each sample is designated as Sample 6-9.

[0051] Example 3

[0052] The crosslinking agent acrylic acid monomer was added to the homogeneous solution of Example 1 and stirred for 1 hour. The remaining powdered solid calcium source, calcium carbonate, was then added to a high-concentration ethylene glycol solution and dispersed with high-speed stirring. The mixture was then added to the solution and mixed evenly. An initiator (dibenzoyl peroxide) was added and stirred until the esterification and crosslinking reactions were complete and a gel was formed. The concentration of the crosslinking agent, the concentration of calcium carbonate in ethylene glycol, and the gel state of the system are shown in Table 3. Each sample is designated as Samples 10-13.

[0053] Example 4

[0054] 10g of commercially available phytic acid and 10.2g of citric acid were added to a beaker, 20mL of water was added and stirred to dissolve, 3.14g of calcium hydroxide was added and stirred for 1h to form a homogeneous solution, 6.29g of calcium hydroxide was dispersed in 31mL of ethylene glycol and added to the homogeneous solution, 2.4g of acrylic acid monomer was then added and stirred for 2h, 0.1g of benzoyl peroxide was added and stirred for 1h, and the mixture was allowed to stand to form a gel, which was dried at 180℃ for 6h to obtain a dry gel. After crushing and calcining at 1500℃ for 9h, a tetracalcium phosphate (TTCP) product was obtained, and its XRD was as follows: Figure 1 shown.

[0055] Example 5

[0056] 10g of commercially available phytic acid and 10.2g of citric acid were added to a beaker, 20mL of water was added and stirred to dissolve, 3.14g of calcium hydroxide was added and stirred for 1h to form a homogeneous solution, 3.93g of calcium hydroxide was dispersed in 20mL of ethylene glycol and added to the homogeneous solution, 2.2g of acrylic acid monomer was then added and stirred for 2h, 0.1g of benzoyl peroxide was added and stirred for 1h, and the mixture was allowed to stand to form a gel, which was dried at 180℃ for 6h to obtain a dry gel. After crushing and calcining at 1400℃ for 3h, the β-tricalcium phosphate (β-TCP) product was obtained, and its XRD was as follows: Figure 2 As shown; then calcined at 1450℃ for 8h, directly quenched to obtain α-tricalcium phosphate (α-TCP) product, its XRD is as shown Figure 3 shown.

[0057] Example 6

[0058] 10g of commercially available phytic acid and 10.2g of citric acid were added to a beaker, 20mL of water was added and stirred to dissolve, 3.14g of calcium hydroxide was added and stirred for 1h to form a homogeneous solution, 4.72g of calcium hydroxide was dispersed in 25mL of ethylene glycol and added to the homogeneous solution, 2.2g of acrylic acid monomer was then added and stirred for 2h, 0.08g of benzoyl peroxide was added and stirred for 1h, the mixture was allowed to stand to form a gel, and dried at 180℃ for 6h. The hydroxyapatite (HA) product was obtained by calcining at 1200℃ for 3h, and its XRD was as follows: Figure 4 shown.

[0059] Example 7

[0060] 10g of commercially available phytic acid and 4.1g of citric acid were added to a beaker, 10mL of water was added and stirred to dissolve, 3.18g of calcium carbonate was added and stirred for 1h to form a homogeneous solution, 9.56g of calcium carbonate was dispersed in 32mL of ethylene glycol and added to the homogeneous solution, 1.6g of acrylic acid monomer was then added and stirred for 2h, 0.06g of benzoyl peroxide was added and stirred for 1h, and the mixture was allowed to stand to form a gel, which was dried at 180℃ for 6h to obtain a dry gel. After crushing and calcining at 1500℃, a tetracalcium phosphate (TTCP) product was obtained, and its SEM was as follows: Figure 5 shown.

[0061] Example 8

[0062] 10g of commercially available phytic acid and 4.1g of citric acid were added to a beaker, and 20mL of water was added with stirring to dissolve. 3.18g of calcium carbonate was then added and stirred for 1 hour to form a homogeneous solution. 6.37g of calcium carbonate was dispersed in 20mL of ethylene glycol and added to the homogeneous solution. 1.4g of acrylic acid monomer was then added and stirred for 2 hours. 0.06g of benzoyl peroxide was then added and stirred for 1 hour. The mixture was allowed to stand until it formed a gel and dried at 180°C for 6 hours to obtain a dry gel. This gel was then pulverized and calcined at 1400°C for 3 hours to obtain the β-tricalcium phosphate (β-TCP) product. This product was then calcined at 1450°C for 8 hours and directly quenched to obtain the α-tricalcium phosphate (α-TCP) product.

[0063] Example 9

[0064] 10 g of commercially available phytic acid and 4.1 g of citric acid were added to a beaker, 20 mL of water was added and stirred to dissolve, 3.18 g of calcium carbonate was added and stirred for 1 hour to form a homogeneous solution, 7.43 g of calcium carbonate was dispersed in 25 mL of ethylene glycol and added to the homogeneous solution, 1.5 g of acrylic acid monomer was then added and stirred for 2 hours, 0.08 g of benzoyl peroxide was added and stirred for 1 hour, and the mixture was allowed to stand to form a gel, dried at 180 ° C for 6 hours, and calcined at 1200 ° C for 3 hours to obtain a hydroxyapatite (HA) product.

[0065] Table 1 Molar ratio of each raw material, pH value of main solution and solution state of Example 1

[0066]

[0067] Table 2 Molar ratio of each raw material, concentration of cross-linking agent and gel state of the system in Example 2

[0068]

[0069] Table 3 Molar ratio of each raw material, calcium carbonate concentration and gel state of the system in Example 3

[0070]

[0071]

[0072] As shown in Tables 1-3 above, by using the raw materials and the ratios of the raw materials within the scope of the present invention, a homogeneous main solution and a gel system can be prepared, so that the reaction materials are mixed evenly, thereby solving the problems of different crystal phases and low purity of the product caused by uneven mixing.

[0073] The above is an exemplary description of the embodiments of the present invention. However, the scope of protection of the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc. made by those skilled in the art within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A method for preparing calcium phosphate bioceramics, characterized in that: The method comprises the following steps: 1) Mixing citric acid, phytic acid, and a portion of a calcium source in water to prepare a main solution; and adding a crosslinking agent to prepare a mixed solution; 2) mixing the remaining calcium source with the esterified dispersant to prepare a calcium pre-dispersant; 3) mixing the calcium pre-dispersant prepared in step 2) and the mixed solution prepared in step 1) with an initiator, and reacting the mixture to prepare a gel; 4) calcining the gel in step 3) to prepare the calcium phosphate bioceramic; The cross-linking agent is acrylic acid; In step 1), the molar ratio of the total molar amount of phytic acid and citric acid to the portion of the calcium source is (0.6-4):1; The molar ratio of the calcium source in step 1) to the calcium source in step 2) is (0.2-1):

1.

2. The method according to claim 1, characterized in that In step 1), the content of the cross-linking agent is 1 wt% to 25 wt% of the total mass of phytic acid, citric acid and calcium source.

3. The method according to claim 1, characterized in that In step 1) or step 2), the calcium source is selected from at least one of calcium oxide, calcium hydroxide, and calcium carbonate.

4. The method according to claim 1, wherein In step 1), the molar ratio of phytic acid to citric acid is 1:(0.7-8).

5. The method according to claim 1, wherein In step 2), the esterification dispersant is ethylene glycol.

6. The method according to claim 1, characterized in that In the calcium pre-dispersant of step 2), the concentration of the calcium source is 10 wt % to 55 wt %.

7. The method according to claim 1, characterized in that In step 3), the initiator is dibenzoyl peroxide; And / or, in step 3), the mass of the initiator is 0.5 wt% to 9 wt% of the cross-linking agent.

8. The method according to claim 1, characterized in that In step 4), the calcination temperature is 900° C. to 1800° C., and the calcination time is 2 h to 12 h.

9. A calcium phosphate bioceramic, characterized in that: The invention is prepared by the method according to any one of claims 1 to 8.

10. The calcium phosphate bioceramic according to claim 9, characterized in that: The calcium phosphate bioceramic is selected from at least one of tetracalcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate and hydroxyapatite.

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