A method for transferring non-polar hydroxyapatite to a polar organic solution phase

Abstract

The present invention discloses a method for transferring non-polar hydroxyapatite to a polar organic solution phase. The method comprises: redispersing HAP prepared by a hydrothermal method in cyclohexane, adding DMF in an equal volume to the cyclohexane, adding nitrosium tetrafluoroborate under stirring conditions, and after vigorous stirring, HAP spontaneously transfers from the cyclohexane phase to the DMF phase. During the ligand exchange process, NO in nitrosium tetrafluoroborate is converted to hydroxyapatite. + Unstable and easily converted into NO2 + , nitrous acid, tetrafluoroboric acid. NO + A large number of conversions in a short period of time will leave a large amount of BF4 in the system ‑ and protons, these acidic protons react with COO ‑ Combined with, reduce the strong coordination effect between oleic acid and Ca element on the surface of HAP particles, thereby promoting BF4 ‑ The present invention uses nitrosium tetrafluoroborate to remove oleic acid from the surface of HAP nanoparticles, BF4 ‑ The electrostatic repulsion effect ensures the uniform dispersion of HAP nanoparticles in DMF. This method is simple to operate and has high transfer efficiency, further expanding the application prospects of HAP nanoparticles.

Description

Technical Field

[0001] The present invention relates to a method for transferring non-polar hydroxyapatite to a polar organic solution phase. Background Art

[0002] Hydroxyapatite (Ca 10 (PO4)6(OH)2, HAP) is the most thermodynamically stable form of calcium phosphate, with excellent biocompatibility and outstanding osteogenic ability. In recent years, HAP has been widely used in biomedical fields such as bone repair, metal implant coating, tooth repair, and drug delivery; it has also performed well in sewage treatment and soil pollution control. In order to meet the huge demand for HAP in scientific research and applications, researchers have developed a variety of methods for preparing HAP, which can be divided into two categories: extraction methods based on biological sources and artificial synthesis methods. Among the many artificial synthesis methods including hydrothermal method, chemical precipitation method, hydrolysis method, solid-phase synthesis method, and sol-gel method, hydrothermal method is widely used due to its good crystallinity and shape control ability.

[0003] Hydrothermal synthesis, as a liquid phase synthesis process induced by thermal energy, is a mature method for bioceramic synthesis. In the oleic acid / ethanol / water system, oleic acid and ethanol act as liquid phases to control the chemical processes occurring on the surface. Under high heat and pressure, the calcium oleate precursor converts Ca 2+ Slowly released into the aqueous reaction solution, with PO4 3- The reaction nucleates and slowly grows. During this process, oleic acid acts as a structural guide for HAP growth along the c-axis. The -COOH group on one end of the oleic acid strongly coordinates with the Ca element on the HAP surface, while the other end is a long, hydrophobic chain. This hydrophobic layer of oleic acid allows HAP to be uniformly dispersed in non-polar solvents such as cyclohexane and toluene, but it cannot be uniformly dispersed as nanoparticles in polar organic solvents, limiting its practical applications.

[0004] Therefore, it is of great significance to develop a simple and efficient method to transfer non-polar HAP prepared by hydrothermal method into polar organic solution phase. Summary of the Invention

[0005] The purpose of the present invention is to develop a method for transferring non-polar hydroxyapatite to a polar organic solution phase in order to address the deficiencies of the prior art. The present invention utilizes nitrosium tetrafluoroborate to protonate the carboxylate ionized in oleic acid, thereby reducing its affinity with Ca 2+ The coordination ability of the system is large, and there is a large amount of BF4 - The dispersion of HAP nanoparticles is ensured and they are transferred to the DMF phase. This method is simple to operate, fast and efficient, and ensures the uniform dispersion of HAP during the phase transfer process.

[0006] The present invention utilizes nitrosium tetrafluoroborate to transfer non-polar hydroxyapatite to a polar organic solution phase. The HAP prepared hydrothermally in an oleic acid / ethanol / water system is coated with a layer of hydrophobic oleic acid molecules, which cannot be dispersed in polar solvents, but can be evenly dispersed in non-polar solvents such as cyclohexane and toluene. After the nitrosium tetrafluoroborate treatment, the oleic acid ligands on the HAP surface are stripped and replaced by BF4 - While ensuring the uniform dispersion of HAP nanoparticles, they were transferred into DMF polar solution, which expanded the application prospects of HAP.

[0007] The preparation method is as follows: HAP prepared by a hydrothermal method is redispersed in cyclohexane, an equal amount of DMF is introduced into the system, and after stirring for 5-10 minutes, an appropriate amount of nitrosonium tetrafluoroborate is added, and the mixture is vigorously stirred for 30-60 minutes. The mixture is allowed to stand and then separated, at which point the HAP has transferred from the cyclohexane phase to the DMF phase.

[0008] Specifically:

[0009] 1) Mix oleic acid and ethanol, introduce a fixed amount of NaOH solution and stir evenly, then add CaCl2 solution dropwise to the system and stir the mixture thoroughly to generate a calcium oleate precursor. Add NaH2PO4 solution dropwise to the mixture and stir thoroughly. Adjust the pH of the solution to above 10 with NaOH solution and transfer to a hydrothermal reactor for hydrothermal mineralization.

[0010] 2) The HAP prepared hydrothermally in the oleic acid / ethanol / water system was centrifuged, redispersed in a cyclohexane solution, and ultrasonically stirred for 0.5-1 h to obtain a brown-yellow transparent solution A;

[0011] 3) Add an equal volume of DMF to solution A and mechanically stir for 5-10 minutes. Introduce nitrosonium tetrafluoroborate equivalent to 1-3 times the mass of HAP in solution A into the system and stir vigorously at a speed of more than 400 rpm for 30-60 minutes to obtain emulsion B;

[0012] 4) Transfer the emulsion to a separatory funnel and allow it to stand until the DMF and cyclohexane phases separate (the upper layer is colorless and transparent, the lower layer is transparent brownish-yellow). The lower layer is the DMF phase in which the nanoparticles are evenly dispersed. Separate the emulsion using a separatory funnel to obtain a DMF solution in which the HAP is evenly dispersed.

[0013] In the above scheme, the HAP prepared by the hydrothermal method in step 1) is preferably 50-200 nm in length and 15-30 nm in diameter. The higher the pH of the system in step 1), the shorter the HAP and the lower the aspect ratio, which facilitates the transfer of the nanoparticles into the polar organic solvent phase. HAP that is too long or has an excessively large aspect ratio will spontaneously assemble into bundles, making it difficult to evenly disperse in cyclohexane and unable to be evenly dispersed in the polar organic solvent phase using nitrosonium tetrafluoroborate.

[0014] Furthermore, in the step 2), the HAP concentration in solution A is 0.5-2 mg / ml.

[0015] Furthermore, in step 3), when nitrosonium tetrafluoroborate is added to solution A at a concentration equivalent to 1-3 times the mass of HAP, the HAP nanoparticles spontaneously transfer to the DMF phase. At concentrations below this, phase transfer is not achieved. When the mass of nitrosonium tetrafluoroborate added is greater than 3 times the mass of HAP, a large amount of nitrosonium tetrafluoroborate remains in the system without participating in the reaction, and the cost is too high.

[0016] The method of the present invention is based on the NO in the nitrosium tetrafluoroborate ligand + Oxidation introduces a large number of protons into the system, and the coordination ability of protonated -COOH with Ca element on the HAP surface is significantly reduced. - The oleic acid ligand on the HAP surface was replaced and the HAP was transferred into the DMF phase. The operation was simple and the transfer efficiency was high.

[0017] The present invention adopts the hydrothermal preparation of HAP using oleic acid / ethanol / water system, which has a layer of oleic acid molecules on its surface, presenting a hydrophobic non-polar state. Then, nitrosium tetrafluoroborate ligand is used to strip the oleic acid, thereby achieving the purpose of uniform dispersion of HAP in polar organic solvents. - The substitution of ligands will not affect the nanodispersibility of HAP particles, and the operation is simple and efficient. - The coordination between the ligand and the Ca element is not particularly strong, so the HAP particle surface can be converted into the required ligand through secondary ligand exchange, and then transferred to a solvent with stronger or weaker polarity to meet the complex needs in actual use. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Schematic diagram of the principle of transferring non-polar HAP into polar organic solution via nitrosonium tetrafluoroborate Figure 2 TEM images of HAP phase transfer prepared at different pH values ​​using different amounts of nitrosium tetrafluoroborate: a) 0.15 g nitrosium tetrafluoroborate, pH = 12; b) 0.3 g nitrosium tetrafluoroborate, pH = 12; c) 0.45 g nitrosium tetrafluoroborate, pH = 12; d) 0.3 g nitrosium tetrafluoroborate, pH = 11; e) 0.3 g nitrosium tetrafluoroborate, pH = 10. DETAILED DESCRIPTION

[0019] The present invention is further described below with reference to the accompanying drawings and specific examples.

[0020] The principle of transferring non-polar HAP to polar organic solution by nitrosonium tetrafluoroborate according to the present invention is as follows: Figure 1As shown. The outer surface of HAP nanoparticles prepared by hydrothermal treatment of oleic acid / ethanol / water system is firmly coated with a layer of hydrophobic oleic acid molecules, which allows HAP to be uniformly dispersed in non-polar solvents such as cyclohexane and toluene, but cannot be uniformly dispersed in polar organic solvents in the form of nanoparticles, which greatly limits the application of HAP in biomedicine, environmental management and other fields. After the introduction of nitrosium tetrafluoroborate into the system, NO + It is easily reduced to NO and then oxidized to NO2 + , nitrous acid, tetrafluoroboric acid. NO in the system + The rapid consumption of BF4 will inevitably lead to a large number of protons and - The production of a large number of protons will coordinate COO with Ca element - Protonation reduces the coordination strength, and a large amount of BF4 - It then coordinates with the exposed Ca element, stabilizing the HAP nanoparticles and preventing them from agglomerating, while simultaneously transferring them to the polar DMF phase. During the phase transfer process, a nitrosonium tetrafluoroborate mass equal to the HAP nanoparticle mass ensures stable phase transfer. A lower mass fails to transfer the HAP to the DMF phase; an excess of nitrosonium tetrafluoroborate introduces a large amount of unreacted impurities into the system, which is also costly.

[0021] Example 1:

[0022] 1) Mix 24 ml of oleic acid and 16 ml of ethanol, add 15 ml of NaOH (10 wt%) solution, and stir for 30 minutes. Add 15 ml of CaCl2 (0.2 mol / L) solution dropwise to the mixture, and continue stirring for 30 minutes. Add 15 ml of NaH2PO4 (0.12 mol / L) solution dropwise to the mixture, and stir for 30 minutes. Adjust the pH of the solution to 12 with NaOH solution, then transfer the solution to a 100 ml hydrothermal reactor and hydrothermally mineralize at 180°C for 36 hours.

[0023] 2) HAP prepared hydrothermally in an oleic acid / ethanol / water system was centrifuged and redispersed in a cyclohexane solution at a concentration of 0.1 mg / ml. Ultrasonic stirring was performed for 1 h to obtain a brownish-yellow transparent solution A.

[0024] 3) Add 150 ml of DMF to 150 ml of solution A, stir mechanically for 5 minutes, introduce 0.15 g of nitrosonium tetrafluoroborate into the system, and stir at a speed of 400 r / min or above for 30 minutes to obtain emulsion B;

[0025] 4) Transfer emulsion B to a separatory funnel and let it stand for 10 minutes. The DMF phase will spontaneously separate from the cyclohexane phase, leaving the lower layer as the DMF phase containing uniformly dispersed HAP nanoparticles. Separate the phases using a separatory funnel to obtain a DMF solution containing uniformly dispersed HAP nanoparticles.

[0026] Example 2:

[0027] 1) Mix 24 ml of oleic acid and 16 ml of ethanol, add 15 ml of NaOH (10 wt%) solution, and stir for 30 minutes. Add 15 ml of CaCl2 (0.2 mol / L) solution dropwise to the mixture, and continue stirring for 30 minutes. Add 15 ml of NaH2PO4 (0.12 mol / L) solution dropwise to the mixture, and stir for 30 minutes. Adjust the pH of the solution to 12 with NaOH solution, then transfer the solution to a 100 ml hydrothermal reactor and hydrothermally mineralize at 180°C for 36 hours.

[0028] 2) HAP prepared hydrothermally in an oleic acid / ethanol / water system was centrifuged and redispersed in a cyclohexane solution at a concentration of 0.1 mg / ml. Ultrasonic stirring was performed for 1 h to obtain a brownish-yellow transparent solution A.

[0029] 3) Add 150 ml of DMF to 150 ml of solution A, stir mechanically for 5 minutes, introduce 0.3 g of nitrosonium tetrafluoroborate into the system, and stir at a speed of 400 r / min or above for 30 minutes to obtain emulsion B;

[0030] 4) Transfer emulsion B to a separatory funnel and let it stand for 10 minutes. The DMF phase will spontaneously separate from the cyclohexane phase, leaving the lower layer as the DMF phase containing uniformly dispersed HAP nanoparticles. Separate the phases using a separatory funnel to obtain a DMF solution containing uniformly dispersed HAP nanoparticles.

[0031] Example 3:

[0032] 1) Mix 24 ml of oleic acid and 16 ml of ethanol, add 15 ml of NaOH (10 wt%) solution, and stir for 30 minutes. Add 15 ml of CaCl2 (0.2 mol / L) solution dropwise to the mixture, and continue stirring for 30 minutes. Add 15 ml of NaH2PO4 (0.12 mol / L) solution dropwise to the mixture, and stir for 30 minutes. Adjust the pH of the solution to 12 with NaOH solution, then transfer the solution to a 100 ml hydrothermal reactor and hydrothermally mineralize at 180°C for 36 hours.

[0033] 2) HAP prepared hydrothermally in an oleic acid / ethanol / water system was centrifuged and redispersed in a cyclohexane solution at a concentration of 0.1 mg / ml. Ultrasonic stirring was performed for 1 h to obtain a brownish-yellow transparent solution A.

[0034] 3) Add 150 ml of DMF to 150 ml of solution A, stir mechanically for 5 minutes, introduce 0.45 g of nitrosonium tetrafluoroborate into the system, and stir at a speed of 400 r / min or above for 30 minutes to obtain emulsion B;

[0035] 4) Transfer emulsion B to a separatory funnel and let it stand for 10 minutes. The DMF phase will spontaneously separate from the cyclohexane phase, leaving the lower layer as the DMF phase containing uniformly dispersed HAP nanoparticles. Separate the phases using a separatory funnel to obtain a DMF solution containing uniformly dispersed HAP nanoparticles.

[0036] Example 4:

[0037] 1) Mix 24 ml of oleic acid and 16 ml of ethanol, add 15 ml of NaOH (10 wt%) solution, and stir for 30 minutes. Add 15 ml of CaCl2 (0.2 mol / L) solution dropwise to the mixture, and continue stirring for 30 minutes. Add 15 ml of NaH2PO4 (0.12 mol / L) solution dropwise to the mixture, and stir for 30 minutes. Adjust the pH of the solution to 10 with NaOH solution, then transfer the solution to a 100 ml hydrothermal reactor and hydrothermally mineralize at 180°C for 36 hours.

[0038] 2) HAP prepared hydrothermally in an oleic acid / ethanol / water system was centrifuged and redispersed in a cyclohexane solution at a concentration of 0.1 mg / ml. Ultrasonic stirring was performed for 1 h to obtain a brownish-yellow transparent solution A.

[0039] 3) Add 150 ml of DMF to 150 ml of solution A, stir mechanically for 5 minutes, introduce 0.3 g of nitrosonium tetrafluoroborate into the system, and stir at a speed of 400 r / min or above for 30 minutes to obtain emulsion B;

[0040] 4) Transfer emulsion B to a separatory funnel and let it stand for 10 minutes. The DMF phase will spontaneously separate from the cyclohexane phase, leaving the lower layer as the DMF phase containing uniformly dispersed HAP nanoparticles. Separate the phases using a separatory funnel to obtain a DMF solution containing uniformly dispersed HAP nanoparticles.

[0041] Example 5:

[0042] 1) Mix 24 ml of oleic acid and 16 ml of ethanol, add 15 ml of NaOH (10 wt%) solution, and stir for 30 minutes. Add 15 ml of CaCl2 (0.2 mol / L) solution dropwise to the mixture, and continue stirring for 30 minutes. Add 15 ml of NaH2PO4 (0.12 mol / L) solution dropwise to the mixture, and stir for 30 minutes. Adjust the pH of the solution to 11 with NaOH solution, then transfer the solution to a 100 ml hydrothermal reactor and hydrothermally mineralize at 180°C for 36 hours.

[0043] 2) HAP prepared hydrothermally in an oleic acid / ethanol / water system was centrifuged and redispersed in a cyclohexane solution at a concentration of 0.1 mg / ml. Ultrasonic stirring was performed for 1 h to obtain a brownish-yellow transparent solution A.

[0044] 3) Add 150 ml of DMF to 150 ml of solution A, stir mechanically for 5 minutes, introduce 0.3 g of nitrosonium tetrafluoroborate into the system, and stir at a speed of 400 r / min or above for 30 minutes to obtain emulsion B;

[0045] 4) Transfer emulsion B to a separatory funnel and let it stand for 10 minutes. The DMF phase will spontaneously separate from the cyclohexane phase, leaving the lower layer as the DMF phase containing uniformly dispersed HAP nanoparticles. Separate the phases using a separatory funnel to obtain a DMF solution containing uniformly dispersed HAP nanoparticles.

Claims

1. A method for transferring non-polar hydroxyapatite to a polar organic solution phase, characterized in that: Nitrosonium tetrafluoroborate was used to remove the strongly coordinated oleic acid molecules on the surface of HAP, and then a large amount of BF4 - Electrostatic stabilization of HAP nanoparticles allows them to transfer from the nonpolar cyclohexane phase to the polar DMF phase; The specific steps include: 1) HAP was prepared by a hydrothermal method: oleic acid and ethanol were mixed, and NaOH solution was introduced and stirred evenly. Then, CaCl2 solution was added dropwise to the system and the mixture was stirred thoroughly to generate a calcium oleate precursor; NaH2PO4 solution was added dropwise to the mixture and stirred thoroughly; The solution pH was adjusted to above 10 using NaOH solution and then transferred to a hydrothermal kettle for hydrothermal mineralization; 2) centrifuging the HAP prepared in step 1), redispersing it in a cyclohexane solution, and stirring it ultrasonically for 0.5-1 h to obtain a brown-yellow transparent solution A; 3) Add an equal volume of DMF to solution A and mechanically stir for 5-10 minutes. Then, add nitrosonium tetrafluoroborate (1-3 times the mass of HAP in solution A) and stir at a speed of 400 rpm or higher for 30-60 minutes to obtain emulsion B. 4) Transferring emulsion B to a separatory funnel and allowing it to stand until the DMF phase and the cyclohexane phase separate, leaving the lower layer as the DMF phase containing uniformly dispersed nanoparticles; separating the emulsions using the separatory funnel to obtain a DMF solution containing uniformly dispersed HAP; the HAP prepared by the hydrothermal method in step 1) has a length of 50-200 nm and a diameter of 15-30 nm.

2. The method for transferring non-polar hydroxyapatite to a polar organic solution phase according to claim 1, wherein: In the step 2), the HAP concentration in solution A is 0.5-2 mg / ml.

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