Octacalcium phosphate pentahydrate nanoflower and preparation method thereof

Abstract

The present invention proposes a pentahydrate octacalcium phosphate nanoflower and a preparation method thereof. Dopamine and a divalent calcium salt solution are added to a phosphate buffer solution of pH 7.5 to 7.8 to form a reaction solution. After being mixed evenly, the mixture is allowed to stand for reaction. The polymerization of dopamine and the growth of crystals are synchronized by controlling the reaction conditions. After the reaction is completed, the precipitate is separated to obtain the pentahydrate octacalcium phosphate nanoflower. The present invention controls the synchronization of dopamine polymerization and crystal growth, and induces the crystal to continue to grow around the crystal nucleus, thereby realizing a nanoflower structure. The present invention is low in cost, and the raw materials used are only phosphate buffer solution, dopamine and divalent calcium salt solution, which has a large raw material cost advantage. The pentahydrate octacalcium phosphate nanoflower produced by the present invention can be widely used in human implant materials, such as fillers or artificial dental implants that replace bones. It has good resorbability and affinity, and has made contributions to human health.

Description

Technical Field

[0001] The invention belongs to the field of nano materials, and relates to a preparation technology of octacalcium phosphate nano materials, and specifically to an octacalcium phosphate pentahydrate nano flower and a preparation method thereof. Background Art

[0002] Hydroxyapatite, also known as hydroxyapatite and basic calcium phosphate, is the main inorganic component of human teeth and bones. Therefore, in the field of filling materials or artificial dental implants to replace damaged bones, it can promote the repair of defective tissues. Hydroxyapatite shows biological activity in the body, stimulates or induces bone hyperplasia, and forms chemical bonds with body tissues at the interface. It is mainly used as a coating to promote bone ingrowth and to increase the proliferation of bone cells. However, hydroxyapatite has the problem that it is difficult to resorb in the body even if bone regeneration is achieved at the damaged site. Therefore, the medical community is conducting research on the role of octacalcium phosphate, a precursor of hydroxyapatite, in improving in vivo resorption and improving the bioaffinity for bone cells. Octacalcium phosphate of different morphologies has a certain influence on reabsorption and affinity. Among the many microscopic morphologies, the nanoflower structure has the largest specific surface area and is theoretically the best microscopic morphology for reabsorption and affinity. However, the existing technology for the synthesis of octacalcium phosphate often obtains nanorods or nanospheres, and it is difficult to obtain nanoflowers. Therefore, it is necessary to find a new process and synthesis method to obtain the nanoflower-like microscopic morphology. Summary of the invention

[0003] The purpose of the present invention is to solve the above problems and propose a method for preparing octacalcium phosphate pentahydrate nanoflowers. By adding dopamine as a crystal forming agent, nano-flower-shaped octacalcium phosphate is obtained, which improves the resorbability and affinity of octacalcium phosphate as a bone filler or dental implant material, and expands the application scope and application market of octacalcium phosphate materials.

[0004] In order to achieve the above object, the present invention adopts the following technical solution:

[0005] A method for preparing octacalcium phosphate pentahydrate nanoflowers comprises the following steps: adding dopamine and a divalent calcium salt solution to a phosphate buffer solution with a pH value of 7.5 to 7.8 to form a reaction solution, mixing the mixture evenly and then standing the mixture for reaction, controlling the reaction conditions to synchronize dopamine polymerization and crystal growth, and separating the precipitate after the reaction to obtain the octacalcium phosphate pentahydrate nanoflowers.

[0006] The reaction condition is mainly the pH value of the phosphate buffer solution.

[0007] Furthermore, the divalent calcium salt solution described in the preparation method includes calcium chloride solution and calcium nitrate solution.

[0008] Furthermore, the phosphate buffer solution with a pH of 7.5 to 7.8 is prepared by mixing a disodium hydrogen phosphate solution and a sodium dihydrogen phosphate solution in a certain proportion.

[0009] The invention controls the growth rate of octacalcium phosphate crystals by the pH value of a phosphate buffer solution, and controls the growth rate of octacalcium phosphate crystals by the concentrations of a divalent calcium salt solution, dopamine and a phosphate buffer solution in a reaction solution, so as to obtain a nano-flower-like morphology crystal structure.

[0010] Furthermore, the configuration ratio of the disodium hydrogen phosphate solution to the sodium dihydrogen phosphate solution is 84:16 to 91.5:8.5.

[0011] Furthermore, in the reaction solution composed of the divalent calcium salt solution, dopamine and phosphate buffer solution, the concentration ratio of the three is 1:1.5-3.25:150-250.

[0012] Furthermore, the calcium ion concentration in the reaction solution is 0.1-0.2 mol / L.

[0013] Furthermore, the static reaction time is 48 to 96 hours.

[0014] Furthermore, after the reaction is completed, the precipitate is separated, washed with water or a volatile solvent, and then dried at 50° C. to 60° C. to obtain octacalcium phosphate pentahydrate nanoflowers.

[0015] Furthermore, the drying is carried out in an oven, and the volatile organic solvent is ethanol.

[0016] The present invention also protects a kind of octacalcium phosphate pentahydrate nanoflower, which is prepared by any one of the above-mentioned preparation methods.

[0017] The present invention also protects the use of octacalcium phosphate pentahydrate nanoflowers for use as fillers for bone replacement or artificial dental implants.

[0018] The control principle of the crystal form of the present invention is as follows:

[0019] During the crystal growth process, the concentration of the reaction solution, temperature and reaction time all have an impact on the crystal morphology. Concentration and time affect the diameter and length of the material, and time also affects the width. In general, the higher the temperature, the longer the diameter of the material, and the better the crystallinity and stability. pH has a huge impact on the morphology. For example, copper phosphate trihydrate can form sheets under acidic phosphate buffer solution and nanoflowers under alkaline conditions. However, the crystal kinetics of different chemical substances are different. For example, manganese phosphate trihydrate nanosheets are not affected by pH. The applicant found in the experiment that for octacalcium phosphate pentahydrate, disc-shaped nanosheets are generated under acidic conditions, and nano-particle crystals (about 10nm) are generated under alkaline conditions. Simply adjusting the crystallization time, concentration and pH value cannot change its morphology, that is, the crystal nucleus will no longer continue to grow after it grows up, such as Figure 1 As shown. The present invention controls the synchronization of dopamine polymerization and crystal growth, inducing the crystal to continue to grow around the crystal nucleus, thereby realizing a nanoflower structure. If the two are not synchronized, the nanoflower structure will not be generated. The main reaction condition affecting dopamine polymerization is the pH value of the phosphate buffer solution. For example, when the pH is 7.2, the self-polymerization speed of dopamine is too slow, and polydopamine induces octacalcium phosphate pentahydrate to grow along the direction of each point, resulting in the production of large flowers with rod-shaped petals with large diameter, thickness and width, such as Figure 2 When pH is 8, dopamine self-polymerizes too fast, and octacalcium phosphate pentahydrate is wrapped by a large number of polydopamine particles, as shown in Figure 3 If octacalcium phosphate pentahydrate is generated first and then dopamine is added, large aggregates are seen, such as Figure 4 shown.

[0020] The synthesis mechanism of using polydopamine to induce octacalcium phosphate pentahydrate nanoparticles to continue growing into nanoflowers is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism of the present invention is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism is different from the cross-linking effect of polydopamine "universal glue" in the prior art. Instead, the synthesis mechanism is different from the cross-linking effect of polydopamine "universal glue" in the prior art. The cross-linking effect ...

[0021] Therefore, the present invention controls the pH of the phosphate buffer solution to 7.5-7.8 to control the polymerization rate of dopamine; controls the concentration of the reaction solution to control the growth rate of octacalcium phosphate crystals. The ratio of the concentrations of the divalent calcium salt solution, dopamine and phosphate buffer solution is 1:1.5-3.25:150-250, and the calcium ion concentration in the reaction solution is 0.1-0.2 mol / L. The structure of the octacalcium phosphate pentahydrate nanoflower is as follows: Figure 5 , XRD pattern and standard XRD pattern of octacalcium phosphate pentahydrate are as follows Figure 6 .

[0022] In addition, whether octacalcium phosphate pentahydrate contains water of crystallization is related to the drying method. The water of crystallization can be removed by heat treatment to form octacalcium phosphate.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The preparation process of the invention is simple and easy to control. Only the pH value and the concentration of the reaction solution need to be controlled to obtain the octacalcium phosphate pentahydrate nanoflowers. The invention can be used in large-scale industrial production and can be widely promoted.

[0025] The invention has low cost, uses only phosphate buffer solution, dopamine and divalent calcium salt solution as raw materials, and has great raw material cost advantage.

[0026] The present invention discovers a new use of dopamine for controlling crystalline magnolia. Through the present invention, the idea of ​​controlling crystalline magnolia with dopamine can be extended to other nanomaterials, providing a new way to control crystalline magnolia.

[0027] The octacalcium phosphate pentahydrate nanoflower produced by the present invention can be widely used in human implant materials, such as fillers for bone replacement or artificial dental implants. It has good resorption and affinity, and contributes to human health. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The SEM images of octacalcium phosphate pentahydrate generated at different pH values ​​without dopamine are shown. Figure 1 (a) is a SEM image of octacalcium phosphate pentahydrate generated at pH 6; Figure 1 (b) is a SEM image of octacalcium phosphate pentahydrate generated at pH 7; Figure 1 (c) is the SEM image of octacalcium phosphate pentahydrate generated at pH 8.

[0029] Figure 2 The SEM image shows that when the pH is 7.2, the self-polymerization rate of dopamine is too slow, and octacalcium phosphate pentahydrate forms a large flower with rod-shaped petals with large diameter, thickness and width.

[0030] Figure 3 It shows that when the pH is 8, the self-polymerization speed of dopamine is too fast, and octacalcium phosphate pentahydrate is wrapped by a large number of polydopamine particles.

[0031] Figure 4 The SEM image shows that octacalcium phosphate pentahydrate was first generated and then dopamine was added, and large agglomerates were observed.

[0032] Figure 5 The SEM image of the polydopamine-induced synthesis of octacalcium phosphate pentahydrate nanoflowers in Example 1 of the present invention is shown.

[0033] Figure 6The XRD spectra of the polydopamine-induced synthesis of octacalcium phosphate pentahydrate nanoflowers in the present invention are shown. (a) is the XRD spectrum of the synthesized octacalcium phosphate pentahydrate nanoflowers; (b) is the standard XRD spectrum of octacalcium phosphate pentahydrate. DETAILED DESCRIPTION

[0034] In order to more clearly understand the above-mentioned purpose, features and advantages of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

[0035] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Therefore, the protection scope of the present invention is not limited to the specific embodiments disclosed below.

[0036] Example 1

[0037] A method for preparing octacalcium phosphate pentahydrate nanoflowers comprises the following experimental steps.

[0038] 16 mL 0.2 mol / L sodium dihydrogen phosphate and 84 mL 0.2 mol / L sodium hydrogen phosphate were mixed to prepare pH 7.5 0.2 mol / L phosphate buffer solution. 1 mg dopamine hydrochloride and 0.5 mL 0.2 mol / L calcium sulfate solution (the ratio of calcium ion, dopamine and phosphate is 1:3.25:200) were added to 100 mL pH 7.5 phosphate buffer solution. After standing for 48 h, the precipitate was obtained by centrifugation. The precipitate was washed twice with distilled water and dried in an oven at 60 °C to obtain octacalcium phosphate trihydrate nanoflowers. Figure 5 .

[0039] Example 2

[0040] A method for preparing octacalcium phosphate pentahydrate nanoflowers comprises the following experimental steps.

[0041] Mix 26mL 0.2mol / L sodium dihydrogen phosphate and 174mL 0.2mol / L sodium hydrogen phosphate to prepare pH 7.60.2mol / L phosphate buffer solution, add 1mg dopamine hydrochloride and 1mL 0.2mol / L calcium sulfate solution (the ratio of calcium ion, dopamine and phosphate is: 1:1.5:200) to 200mL pH 7.6 phosphate buffer solution at the same time, let it stand for 48h, centrifuge to obtain a precipitate, wash it twice with distilled water, and dry it in a 60℃ oven to obtain octacalcium phosphate trihydrate nanoflowers.

[0042] Example 3

[0043] A method for preparing octacalcium phosphate pentahydrate nanoflowers comprises the following experimental steps.

[0044] Mix 10.5mL 0.2mol / L sodium dihydrogen phosphate and 89.5mL 0.2mol / L sodium hydrogen phosphate to prepare pH 7.70.2mol / L phosphate buffer solution, add 0.5mg dopamine hydrochloride and 0.5mL 0.2mol / L calcium sulfate solution (the ratio of calcium ion, dopamine and phosphate is: 1:1.5:200) to 100mL pH 7.7 phosphate buffer solution at the same time, let it stand for 72h, centrifuge to obtain a precipitate, wash it twice with ethanol, and dry it in a 50℃ oven to obtain octacalcium phosphate trihydrate nanoflowers.

[0045] Example 4

[0046] A method for preparing octacalcium phosphate pentahydrate nanoflowers comprises the following experimental steps.

[0047] Mix 16mL 0.1mol / L sodium dihydrogen phosphate and 84mL 0.1mol / L sodium hydrogen phosphate to prepare pH 7.5 0.1mol / L phosphate buffer solution, add 0.5mg dopamine hydrochloride and 0.5mL 0.1mol / L calcium sulfate solution (the ratio of calcium ion, dopamine and phosphate is: 1:3.25:200) to 100mL pH 7.5 phosphate buffer solution at the same time, let it stand for 72h, centrifuge to obtain a precipitate, wash it twice with ethanol, and dry it in a 60℃ oven to obtain octacalcium phosphate trihydrate nanoflowers.

[0048] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing octacalcium phosphate pentahydrate nanoflowers, characterized in that: Dopamine and divalent calcium salt solution are added to a phosphate buffer solution of pH 7.5-7.7 to form a reaction solution, which is mixed evenly and then allowed to react for 48-96 hours. The polymerization of dopamine and crystal growth are synchronized by controlling the reaction conditions. After the reaction is completed, the precipitate is separated to obtain octacalcium phosphate pentahydrate nanoflowers. The phosphate buffer solution of pH 7.5-7.7 is prepared by mixing disodium hydrogen phosphate solution and sodium dihydrogen phosphate solution in a ratio of 84:16-91.5:8.5; In the reaction solution composed of the divalent calcium salt solution, dopamine and phosphate buffer solution, the concentration ratio of the three is 1:1.5-3.25:150-250 according to the ratio of calcium ion, dopamine and phosphate; The calcium ion concentration in the reaction solution is 0.1-0.2 mol / L.

2. The method for preparing octacalcium phosphate pentahydrate nanoflowers according to claim 1, characterized in that: The divalent calcium salt solution described in the preparation method includes calcium chloride solution and calcium nitrate solution.

3. The method for preparing octacalcium phosphate pentahydrate nanoflowers according to claim 1, characterized in that: After the reaction is completed, the precipitate is separated, washed with water or a volatile solvent, and then dried at 50° C. to obtain octacalcium phosphate pentahydrate nanoflowers.

4. Use of the preparation method according to any one of claims 1 to 3, characterized in that: Fillings or dental implants used to replace bone.

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