Method for preparing suspension of layered double hydroxide particles

Abstract

The invention relates to a method for preparing a suspension of layered double hydroxide particles, which comprises the following steps: putting a solution containing a layered double hydroxide precursor into heat preservation equipment for heat locking treatment, and reacting to obtain the suspension of the layered double hydroxide particles, in the heat locking treatment, the temperature is maintained only through heat preservation equipment under the normal pressure condition. The method disclosed by the invention has the beneficial effects that the locking heat treatment is carried out through heat preservation equipment, the layered double hydroxide precursor does not need to be continuously heated and pressurized, and the high-quality layered double hydroxide particles with high crystallinity and uniform morphology can still be synthesized under the condition of normal pressure.

Description

Technical Field

[0001] This invention belongs to the field of nanoparticle preparation technology, and particularly relates to a method for preparing a suspension of layered double hydroxide particles. Background Technology

[0002] Layered double hydroxides (LDHs), also known as hydrotalcite nanoparticles, have shown great promise in recent years across various cutting-edge fields due to their unique layered structure, tunable chemical composition, and surface charge properties. Hydrotalcite nanoparticles have become a research hotspot, particularly in the fields of pharmaceuticals, vaccines, drug delivery, and catalysis. For example, in drug delivery systems, their layered structure can significantly improve drug stability, sustained release, targeting, and phagocytosis through intercalation or surface adsorption. In vaccine adjuvants, hydrotalcite, with its biocompatibility and immune-activating capabilities, can effectively enhance the immune response to antigens. In catalysis, its high specific surface area and tunable active sites make it a highly efficient catalyst or catalyst support.

[0003] The properties of hydrotalcite are closely related to its chemical composition, especially the presence of divalent metal ions (such as Mg). 2+ Zn 2+ Cu 2+ Co 2+ Ni 2+ (etc.) and trivalent metal ions (such as Al) 3+ Fe 3+ Ce 3+ The types and doping ratios of metal ions (such as divalent and trivalent metal ions) can be varied. Different combinations of metal ions can endow hydrotalcite with unique physicochemical properties. By adjusting the molar ratio of divalent to trivalent metal ions in hydrotalcite, the charge density of the layers, the interlayer spacing, and the surface active sites can be precisely controlled, thereby optimizing its functional properties.

[0004] Despite the promising applications of hydrotalcite, its low-cost preparation remains a challenge. The traditional hydrothermal method (PCT / AU2005 / 001948) is the mainstream technique for synthesizing high-quality hydrotalcite nanoparticles. This method involves dissolving, transforming, and crystallizing reactants in a high-temperature, high-pressure, closed environment using water or an organic solvent as a medium. The "hydrothermal" in its name comes from the experimental environment itself—heating + solvent (usually water). During the reaction, as the temperature rises, the pressure in the closed container continuously increases, and the reactants undergo a dissolution-transportation-recrystallization process under high temperature and pressure, resulting in nanocrystalline or single-crystal materials with controllable particle size and good dispersibility. Therefore, this method relies on high-pressure reactors and precise temperature control equipment (such as constant-temperature ovens), which leads to high equipment costs and complex operation. Furthermore, limited by the limited reactor volume (typically tens to hundreds of milliliters), this method can only be used for small-scale preparation of hydrotalcite nanoparticles, making it difficult to meet industrial-scale demands. To increase yield, some studies have attempted to scale up the reactor, but equipment costs increase exponentially, and the uniformity of the prepared particles is difficult to guarantee. Although some improved methods (such as co-precipitation) have been reported to increase yield, the resulting hydrotalcite nanoparticles exhibit inconsistent crystallinity and wide particle size distribution, leading to uneven product quality and making it difficult to meet the demands of refined applications in biomedicine and catalysis. Therefore, developing a low-cost, efficient, easily scalable synthesis process that yields stable-quality hydrotalcite nanoparticles is crucial for advancing the industrial application of hydrotalcite nanoparticles. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for preparing a suspension of layered double hydroxide particles.

[0006] In a first aspect, a method for preparing a suspension of layered double hydroxide particles is provided, comprising:

[0007] A solution containing the layered double hydroxide precursor is placed in a heat-locking device for heat preservation treatment, and a suspension of layered double hydroxide particles is obtained by reaction; the heat preservation treatment is to maintain the temperature only by the heat preservation device under normal pressure.

[0008] In some embodiments, the solution containing the layered double hydroxide precursor is maintained at a temperature of 30–100°C in the insulation device; in some embodiments, the layered double hydroxide precursor is maintained at a temperature of 50–80°C in the insulation device.

[0009] In some embodiments, the solution containing the layered double hydroxide precursor is placed in an insulated device without the need for continuous external heating and / or pressurization.

[0010] In some embodiments, the heat-locking treatment time is ≥1 hour; the heat-locking treatment time is 1 to 16 hours.

[0011] In some embodiments, a solution containing the layered double hydroxide precursor is transferred to a preheatable container, the preheatable container containing the layered double hydroxide precursor is preheated to a target temperature, and a heat-preserving reaction is performed to obtain a suspension of the layered double hydroxide particles.

[0012] In some embodiments, the preheatable container is a stand-alone container adapted to the insulation equipment.

[0013] In some embodiments, the insulation device includes an insulated housing for maintaining the temperature inside the preheatable container.

[0014] In some embodiments, the raw materials used to prepare the layered double hydroxide precursor include mixed metal ions; the raw materials used to prepare the layered double hydroxide precursor include mixed metal ions.

[0015] In some embodiments, the mixed metal ions include divalent metal ions and trivalent metal ions.

[0016] In some embodiments, the divalent metal ion includes Mg 2+ Zn 2+ Cu 2+ Co 2+ Ni 2+ At least one of them.

[0017] In some embodiments, the trivalent metal ions include Al 3+ Fe 3+ and Ce 3+ At least one of them.

[0018] In some embodiments, the molar ratio of the divalent metal ion to the trivalent metal ion is 1:1 to 10:1.

[0019] In some embodiments, the raw materials used to prepare the layered double hydroxide precursor further include a basic compound.

[0020] In some embodiments, the alkaline compound includes at least one selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and ammonia.

[0021] In some embodiments, the molar ratio of the alkaline compound to the mixed metal ions is 1.5:1 to 10:1.

[0022] In some embodiments, the alkaline compound is mixed with mixed metal ions and then reacted in an environment of 0–50°C to obtain the layered double hydroxide precursor.

[0023] In some embodiments, after the alkaline compound is mixed with the mixed metal ions, the container containing the alkaline compound and the mixed metal ions is placed in an ice-water bath to react and obtain the layered double hydroxide precursor.

[0024] In some embodiments, a method for preparing the layered double hydroxide precursor includes: preparing a layered double hydroxide precipitate by co-precipitation to form a mixture of the layered double hydroxide precipitate and a solution containing the layered double hydroxide precursor.

[0025] In some embodiments, the contact time between the layered double hydroxide precipitate and the solution does not exceed 30 minutes.

[0026] In some embodiments, the temperature of the coprecipitation reaction is ≤50°C.

[0027] In some embodiments, the solution is further used to separate the layered double hydroxide precipitate.

[0028] In some embodiments, the process further includes washing the layered double hydroxide precipitate.

[0029] In some embodiments, the method further includes mixing the washed layered double hydroxide precipitate with a solvent to obtain the solution containing the layered double hydroxide precursor.

[0030] In some embodiments, the solvent in the solution containing the layered double hydroxide precursor includes at least one of water, methanol, ethanol, and an electrolyte solution.

[0031] In some embodiments, the solution is a mixture of a solution containing mixed metal ions and a solution containing an alkaline compound, and the reaction produces a precipitate, which is the layered double hydroxide precursor.

[0032] In some embodiments, the solvent in the solution containing mixed metal ions and the solution containing alkaline compounds each independently includes at least one of water, methanol, ethanol, and electrolyte solution.

[0033] In a second aspect, a suspension of layered double hydroxide particles prepared by any of the methods described in the first aspect is provided.

[0034] Thirdly, a drug delivery system is provided, comprising a suspension of the layered double hydroxide particles described in the second aspect.

[0035] Fourthly, a drug is provided, comprising a suspension of layered double hydroxide particles as described in the second aspect, or a drug delivery system as described in the third aspect.

[0036] Fifthly, a vaccine is provided, comprising a suspension of the layered double hydroxide particles described in the second aspect.

[0037] In a sixth aspect, a catalyst is provided comprising a suspension of layered double hydroxide particles as described in the second aspect.

[0038] Compared with the prior art, in some embodiments, the beneficial effects of the present invention include:

[0039] 1) Low-cost, scale-controlled preparation of hydrotalcite nanoparticles: In some embodiments, small to medium-scale preparation of 0.001-50L layered double hydroxide particles can be achieved, with a maximum single yield hundreds of times that of the traditional hydrothermal method (typically <0.1L), and without the need for high-pressure reactors and precision temperature control equipment, significantly reducing equipment costs.

[0040] 2) Simple and efficient process: The reaction process only controls the initial temperature of the suspension of layered double hydroxide precursor particles and the preheatable container (inner liner) and the heat-locking reaction time. During the heat-locking process in conventional heat-insulating equipment, the effect of temperature changes on the morphology, particle size and crystals of the final product is negligible. There is no need for constant temperature ovens or precision temperature control systems for continuous external heating or pressurization. Therefore, the operation threshold is low and it is easy to scale up industrially.

[0041] 3) Stable product performance: The obtained layered double hydroxide particles maintain a hexagonal plate-like morphology and narrow particle size distribution (PDI ~ 0.2), and the crystallinity is comparable to that of the traditional hydrothermal method, meeting the high standard requirements of the pharmaceutical, catalysis and other fields.

[0042] 4) Significant cost advantage: The cost of conventional insulation equipment is less than 1 / 10 of that of a high-pressure reactor, and it requires no frequent maintenance. The reaction process also does not require continuous heating or pressurization, saving production energy and significantly reducing overall production costs.

[0043] 5) Simple and safe operation: The overall operating temperature does not exceed 100℃ and the operating pressure is at atmospheric pressure, making it safe and controllable. Attached Figure Description

[0044] Figure 1 This is a schematic diagram of the main operation process of the present invention;

[0045] Figure 2 Transmission electron microscopy (TEM) image of Mg3Al-LDH nanoparticles prepared in Comparative Example 1;

[0046] Figure 3 The image shows the dynamic light scattering (DLS) detection of the particle size of Mg3Al-LDH nanoparticles obtained at an initial temperature of 100℃ for different holding times in Example 1.

[0047] Figure 4The image shows a TEM image of Mg3Al-LDH nanoparticles obtained in Example 1 after a heat treatment at an initial temperature of 100°C for 6 hours.

[0048] Figure 5 The X-ray diffraction (XRD) patterns of Mg3Al-LDH nanoparticles obtained by initial temperature of 100℃ and heat treatment for 6 hours in Example 1 and Mg3Al-LDH hydrotalcite nanoparticles prepared by conventional hydrothermal method are shown.

[0049] Figure 6 The temperature-time curves of the hydrotalcite precursors with different initial temperatures in a conventional insulation device in Example 2 are shown.

[0050] Figure 7 This is a DLS image of the particle size of Mg3Al-LDH nanoparticles obtained after 6 hours of heat treatment at different initial temperatures in Example 2.

[0051] Figure 8 This is a DLS image of the particle size of Mg3Al-LDH nanoparticles with different mass concentrations obtained in Example 3 after being kept at an initial temperature of 100℃ for 6 hours.

[0052] Figure 9 The image shows the DLS measurements of the particle size of Mg3Al-LDH hydrotalcite nanoparticles prepared using insulation equipment of different sizes in Example 4.

[0053] Figure 10 The image shows the DLS detection of the particle size of Mg3Al-LDH nanoparticles with different anions prepared in Example 5 by holding at an initial temperature of 100℃ for 6 hours.

[0054] Figure 11 This is a DLS image of the particle size of MgAl-LDH nanoparticles prepared in Example 6 by holding at an initial temperature of 100°C for 6 hours using a mixed solution of divalent and trivalent metal salts with different molar ratios as raw materials.

[0055] Figure 12 The image shows the DLS detection of the particle size of hydrotalcite nanoparticles containing different metal ions prepared in Example 7 by holding at an initial temperature of 100°C for 6 hours.

[0056] Figure 13 The image shows the DLS detection of the particle size of the hydrotalcite nanoparticles containing two different divalent metal ions prepared in Example 8 by holding at an initial temperature of 100°C for 6 hours.

[0057] Figure 14 TEM image of the particle size of hydrotalcite nanoparticles containing two different divalent metal ions prepared in Example 8 by holding at an initial temperature of 100°C for 6 hours.

[0058] Figure 15 The image shows the DLS detection of the particle size of the hydrotalcite nanoparticles containing two different trivalent metal ions prepared in Example 9 by holding at an initial temperature of 100°C for 6 hours.

[0059] Figure 16 The image shows the DLS (Dielectric Strength Analysis) plots of the particle sizes of hydrotalcite (Mg3Fe-LDH) nanoparticles with different trivalent metal ions prepared in Example 10 by holding at an initial temperature of 100°C for 6 hours. Detailed Implementation

[0060] In the traditional field of hydrotalcite synthesis, it is generally believed that high temperature (>100℃) and high pressure (5-10 atmospheres) are necessary conditions for preparing hydrotalcite nanoparticles with high crystallinity and uniform morphology. Without a high-temperature environment, crystal growth kinetics are insufficient—ion diffusion is slow at low temperatures, and crystal growth may be incomplete; without a high-pressure environment, the boiling point of water is too low to create a high-temperature environment. Furthermore, it is generally believed in the traditional field that high pressure is necessary to inhibit Ostwald ripening. This technological bias has long constrained the low-cost, large-scale production of hydrotalcite. Unexpectedly, in some embodiments of this invention, heat-locking treatment using a thermal insulation device eliminates the need for continuous heating and pressurization of the layered double hydroxide precursor, allowing the synthesis of high-crystallinity, high-quality hydrotalcite nanoparticles with uniform morphology under ambient pressure. This breakthrough discovery overcomes the technological bias in the field that high-quality hydrotalcite cannot be prepared at low temperatures and ambient pressure, providing a completely new path for large-scale production.

[0061] In some embodiments, the desired hydrotalcite nanomaterials can be obtained by further optimizing the metal salt ratio, alkali concentration, and heat retention time.

[0062] Specifically, this application provides a method for preparing hydrotalcite nanomaterials on a small to medium scale using a heat-locking method. By optimizing the metal salt ratio, reaction conditions, and equipment selection, the synthesis efficiency and yield of hydrotalcite nanoparticles are significantly improved, while reducing equipment and preparation costs. Figure 1 As shown, the method includes:

[0063] S1. Preparation of layered double hydroxide precursor (i.e., hydrotalcite precursor).

[0064] In S1, the raw materials used to prepare the layered double hydroxide precursor include mixed metal ions, which include divalent and trivalent metal ions; the divalent metal ions include Mg. 2+ Zn 2+ Cu 2+ Co 2+ Ni 2+ At least one of the following; the trivalent metal ions include Al 3+ Fe3+ and Ce 3+ At least one of the following; the molar ratio of the divalent metal ion to the trivalent metal ion is 1:1 to 10:1.

[0065] In step S1, the raw materials used to prepare the layered double hydroxide precursor also include an alkaline compound; the alkaline compound includes at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and ammonia; the molar ratio of the alkaline compound to the mixed metal ions is 1.5:1 to 10:1, preferably 2:1. After mixing the alkaline compound and the mixed metal ions, the mixture reacts in an environment of 0–50°C to obtain the layered double hydroxide precursor. For example, the alkaline compound and the mixed metal ions are reacted in an ice-water bath (0°C) to obtain the layered double hydroxide precursor. The difference between the ice-water bath and room temperature conditions lies in controlling the nucleation and growth kinetics, which directly affects the crystal structure, particle size, particle size distribution, specific surface area, and chemical homogeneity of the final product. The core advantage of the ice-water bath is that it achieves "nucleation control" through high supersaturation and low growth rate, thereby obtaining a layered double hydroxide precursor with small size, narrow distribution, and uniform composition.

[0066] In S1, the preparation of the layered double hydroxide precursor includes:

[0067] Layered double hydroxide precipitates are prepared by co-precipitation to form a mixture of the layered double hydroxide precipitate and a solution containing the layered double hydroxide precursor; the contact time between the layered double hydroxide precipitate and the solution does not exceed 30 minutes.

[0068] In S1, the preparation of the layered double hydroxide precursor further includes:

[0069] Separate the layered double hydroxide precipitate from the solution.

[0070] For example, a mixed salt solution is prepared by mixing divalent and trivalent metal salts at different molar ratios; simultaneously, a corresponding alkaline solution is prepared. The mixed salt solution is added to the prepared alkaline solution, stirred, centrifuged, and the precipitate is collected and resuspended as a suspension of the hydrotalcite precursor product. The pH of the alkaline solution is between 7.01 and 12.00. The alkaline solution can be a single-component solution prepared from the aforementioned alkaline compound, or a mixed solution of the aforementioned alkaline compound with one or more of sodium chloride, sodium sulfate, sodium carbonate, sodium nitrate, and sodium thiosulfate. The stirring time between the mixed salt solution and the alkaline solution is between 1 and 120 minutes, and the stirring method (tool, speed, etc.) is not limited. The solvents for washing and resuspending the hydrotalcite precursor product include, but are not limited to, water, methanol, ethanol, and electrolyte solutions. The concentration of the hydrotalcite precursor product suspension is between 0.01 and 100 mg / mL, preferably between 0.1 and 10 mg / mL.

[0071] S2. The layered double hydroxide precursor is subjected to heat-locking treatment in a heat-insulating device to obtain a suspension of layered double hydroxide particles; the heat-locking treatment is to maintain the temperature at 60-100°C for 1-16 hours under normal pressure by using a heat-insulating device, without the need for continuous external heating or pressurization.

[0072] In step S2, the layered double hydroxide precursor is transferred to a preheatable container, and the preheatable container containing the layered double hydroxide precursor is preheated to the target temperature for a heat preservation reaction to obtain a suspension of the layered double hydroxide particles.

[0073] In S2, the preheatable container is an independent container adapted to the heat preservation equipment; the heat preservation equipment includes a heat-insulating shell for maintaining the temperature inside the preheatable container.

[0074] The subcritical temperature of 60–100°C (lower than the traditional hydrothermal temperature of 120–200°C) avoids morphological defects and particle agglomeration caused by violent reactions while ensuring sufficient crystal growth. This application also compensates for crystal growth kinetics by extending the holding time. For example, a gradient design of 1–16 hours is suitable for the crystallization requirements of different metal combinations. Shorter times (e.g., 1–4 hours) are suitable for highly reactive metal systems, while longer times (e.g., 12–16 hours) are beneficial for the synthesis of highly stable materials. Furthermore, the heat-locking design prevents sudden temperature drops and maintains slow crystal growth.

[0075] For example, the heat preservation equipment can be readily available household appliances, including but not limited to slow cookers, thermos pots, and insulated boxes, or it can be specially customized equipment or facilities for heat preservation purposes. The preheating container is the inner liner of the heat preservation equipment. In S2, a certain volume of hydrotalcite precursor product suspension is added to the inner liner of the heat preservation equipment. The inner liner and the hydrotalcite precursor product suspension are preheated together to a specified temperature and then sealed for heat preservation treatment to obtain a hydrotalcite nanoparticle product suspension. The heat preservation treatment involves maintaining the temperature solely through the heat preservation equipment under normal pressure conditions, without the need for continuous external heating or pressurization. Finally, the inner liner containing the hydrotalcite precursor product suspension is removed, and after natural cooling, a hydrotalcite nanoparticle product suspension is obtained. Compared with traditional high-pressure reactors, the large-capacity design (up to 50L) of conventional heat preservation equipment significantly increases the yield per batch, and the particle size, morphology, and crystallinity of the obtained hydrotalcite nanoparticles are basically consistent with those obtained by traditional hydrothermal methods (e.g., Figure 2 (As shown). In the prior art, the commonly used size of high-pressure reactors is less than 0.1L, and as the volume increases, the cost increases significantly.

[0076] In addition, such as Figure 1As shown, in one optional implementation, the hydrotalcite precursor product suspension is directly added to the inner liner, the material of which is not limited. In another optional implementation, the hydrotalcite precursor product suspension and its original container (such as a beaker) are placed in a water-filled inner liner adapted to conventional insulation equipment. The volume of the hydrotalcite precursor product suspension is between 0.001-50L, preferably 0.1-10L.

[0077] As can be seen, the embodiments of this application significantly improve the synthesis efficiency and yield of hydrotalcite by optimizing the metal salt ratio, reaction conditions, and equipment selection, while reducing equipment and preparation costs. In some embodiments, the material prepared by this invention has the structural characteristics of a two-dimensional material, and the preparation method is simple, easy to implement, has a simple reaction, and a large yield. The invention will be described in detail below with reference to the embodiments. The following embodiments will help those skilled in the art to further understand the invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make several adjustments and improvements without departing from the concept of the invention. These all fall within the protection scope of the invention.

[0078] Example 1: Preparation of Mg3Al-LDH hydrotalcite nanoparticles with different holding times

[0079] (1) Dissolve 15 mmol MgCl2·6H2O in 25 mL of ultrapure water to obtain an aqueous solution of magnesium chloride; dissolve 5 mmol AlCl3·6H2O in 25 mL of ultrapure water to obtain an aqueous solution of aluminum chloride; then mix them to obtain a mixed salt solution; dissolve 40 mmol sodium hydroxide in 70 mL of ultrapure water; mix the mixed salt solution and sodium hydroxide solution in an ice-water bath (0 °C) with rapid stirring and continue stirring for 30 minutes, centrifuge at 4750 g to remove the supernatant, then wash twice with ultrapure water and resuspend in 400 mL of ultrapure water to obtain a Mg3Al-LDH hydrotalcite precursor with a concentration of about 2 mg / mL, and transfer it to the inner liner.

[0080] (2) The inner liner containing the LDH precursor product was preheated to 100°C and then placed in a conventional heat-insulating device for heat retention treatment. After different times (2, 4, 6, 8, 16, 48, 72 hours), the inner liner was removed and cooled to room temperature to obtain Mg3Al-LDH hydrotalcite nanoparticles. The particle size distribution of the hydrotalcite nanoparticles was determined using DLS. Figure 3 The nanoparticle sizes shown are 50±20 nm, 80±10 nm, 100±10 nm, 105±10 nm, 120±10 nm, 135±10 nm, and 140±10 nm, respectively. The particle size of the prepared MgAl-LDH hydrotalcite nanoparticles increased slightly with time. (The same applies below.) Figure 3Particles larger than 500 nm (i.e., incompletely dispersed hydrotalcite particle aggregates) can be removed by centrifugation at 2000–6000 g for 5 minutes, and the supernatant is collected to obtain a suspension of monodisperse hydrotalcite nanoparticles.

[0081] After 6 hours of heat treatment, the synthesized hydrotalcite nanoparticles have the following morphology: Figure 4 The TEM images show a hexagonal layered structure. The morphology of the Mg3Al-LDH hydrotalcite synthesized over 6 hours with thermal insufficiency is almost identical to that of the comparative sample prepared by the conventional hydrothermal method. Figure 5 The XRD results show that the hydrotalcite nanoparticles synthesized by the thermal locking method in this embodiment have the same crystal structure as the hydrotalcite nanoparticles synthesized by the traditional hydrothermal method.

[0082] Example 2: Preparation of Mg3Al-LDH nanoparticles by holding at different initial temperatures for 6 hours

[0083] (1) Dissolve 15 mmol MgCl2·6H2O in 25 mL of ultrapure water to obtain an aqueous solution of magnesium chloride; dissolve 5 mmol AlCl3·6H2O in 25 mL of ultrapure water to obtain an aqueous solution of aluminum chloride; then mix them to obtain a mixed salt solution; dissolve 40 mmol sodium hydroxide in 70 mL of ultrapure water; mix the mixed salt solution and sodium hydroxide solution in an ice-water bath with rapid stirring and continue stirring for 30 minutes, centrifuge at 4750g to remove the supernatant, then wash twice with ultrapure water, and resuspend in 400 mL of ultrapure water to obtain a Mg3Al-LDH hydrotalcite precursor with a concentration of about 2 mg / mL, and transfer it to the inner liner.

[0084] (2) The inner liner containing the LDH precursor product was preheated to 100°C, 80°C and 60°C. The temperature of the aqueous solution in the inner liner at different time points was recorded at different initial temperatures. Figure 6 The curve shows the temperature of the hydrotalcite precursor product suspension over time.

[0085] (3) The preheated inner liner was placed in a conventional insulation device for heat preservation. After 6 hours of heat preservation, the inner liner was removed and cooled to room temperature to obtain Mg3Al-LDH hydrotalcite nanoparticles. Figure 7 As shown, after initial conventional insulation temperatures of 100, 90, 80, 70, and 60°C for 6 hours, the average particle sizes of the synthesized hydrotalcite nanoparticles were approximately 100±10 nm, 95±20 nm, 92±20 nm, 80±25 nm, and 70±30 nm, respectively. This result indicates that the initial temperature has a certain influence on the average particle size and uniformity. Higher temperatures result in better uniformity, but also larger particle sizes.

[0086] Example 3: Mg3Al-LDH hydrotalcite nanoparticles prepared with different hydrotalcite precursor concentrations

[0087] (1) 15 mmol MgCl2·6H2O was dissolved in 25 mL of ultrapure water to obtain an aqueous solution of magnesium chloride; 5 mmol AlCl3·6H2O was dissolved in 25 mL of ultrapure water to obtain an aqueous solution of aluminum chloride; then they were mixed to obtain a mixed salt solution; 40 mmol sodium hydroxide was dissolved in 70 mL of ultrapure water; the mixed salt solution and sodium hydroxide solution were mixed in an ice-water bath with rapid stirring and continued stirring for 30 min; the supernatant was removed by centrifugation at 4750 g; then the mixture was washed twice with ultrapure water and resuspended with different volumes of ultrapure water to obtain Mg3Al-LDH hydrotalcite precursor products with concentrations of approximately 1, 2, 4 and 8 mg / mL, and transferred to the inner liner.

[0088] (2) The inner liner containing the LDH precursor product was preheated to 100°C, and then kept at that temperature using conventional insulation equipment. After 6 hours of insulation, the inner liner was removed and cooled to room temperature to obtain Mg3Al-LDH hydrotalcite nanoparticles. Figure 8 As shown, the average particle size of the synthesized hydrotalcite nanoparticles was approximately 70 ± 10 nm at concentrations of 1, 2, 4, and 8 mg / mL. This indicates that different hydrotalcite precursor concentrations have little effect on the final nanoparticle size.

[0089] Example 4: Mg3Al-LDH hydrotalcite nanoparticles prepared by insulation equipment of different sizes

[0090] (1) Dissolve 75 mmol MgCl2·6H2O in 125 mL of ultrapure water to obtain an aqueous solution of magnesium chloride; dissolve 25 mmol AlCl3·6H2O in 125 mL of ultrapure water to obtain an aqueous solution of aluminum chloride; then mix them to obtain a mixed salt solution; dissolve 200 mmol sodium hydroxide in 350 mL of ultrapure water; mix the mixed salt solution and sodium hydroxide solution in an ice-water bath with rapid stirring and continue stirring for 30 minutes, centrifuge at 4750 g to remove the supernatant, then wash twice with ultrapure water and resuspend in 5 L of ultrapure water to obtain a Mg3Al-LDH hydrotalcite precursor product with a concentration of about 1 mg / mL, and transfer 100 mL, 400 mL and 4 L of the Mg3Al-LDH hydrotalcite precursor product to the corresponding specifications (1 L, 1 L and 5 L) of the inner liner.

[0091] (2) The inner liner containing the LDH precursor product was preheated to 100°C, and then kept at that temperature using conventional insulation equipment. After 6 hours of insulation, the inner liner was removed and cooled to room temperature to obtain Mg3Al-LDH hydrotalcite nanoparticles. Figure 9As shown, the particle size of the hydrotalcite nanoparticles prepared on a medium scale using different types of insulation equipment is approximately 70 ± 10 nm. This indicates that the heat-locking method can be used to prepare hydrotalcite nanoparticles on a small to medium scale.

[0092] Example 5: Mg3Al-LDH hydrotalcite nanoparticles with different anion intercalations

[0093] (1) 15 mmol MgCl2·6H2O was dispersed in 25 mL of ultrapure water to obtain an aqueous solution of magnesium chloride; 5 mmol AlCl3·6H2O was dispersed in 25 mL of ultrapure water to obtain an aqueous solution of aluminum chloride; then the solutions were mixed to obtain a mixed salt solution; 40 mmol sodium hydroxide and 2.5 mmol Na2SO4, Na2CO3, NaNO3, and Na2S2O3 were dispersed in 70 mL of ultrapure water; under nitrogen protection, the mixed salt solution and the mixture of sodium hydroxide and different sodium salt solutions were stirred and mixed in an ice-water bath and stirred for 30 minutes. The supernatant was removed by centrifugation at 4750 g, and then the solution was washed twice with ultrapure water and resuspended in 400 mL of ultrapure water to obtain a Mg3Al-LDH hydrotalcite precursor with a concentration of about 2 mg / mL containing different anion intercalations, which was then transferred to the inner liner.

[0094] (2) The inner liner containing the LDH precursor product suspension was preheated to 100°C and then placed in a conventional heat preservation device for heat preservation. After heat preservation for 6 hours, the inner liner was removed and cooled to room temperature to obtain Mg3Al-LDH hydrotalcite nanoparticles.

[0095] The particle size distribution of Mg3Al-LDH hydrotalcite nanoparticles with different anion intercalations was analyzed by DLS. For example... Figure 10 As shown, the average particle sizes of Mg3Al-SO4-LDH, Mg3Al-CO3-LDH, Mg3Al-NO3-LDH, and Mg3Al-S2O3-LDH with different anion intercalations are 120±5 nm, 150±10 nm, 160±10 nm, and 150±10 nm, respectively. This indicates that different anions have a certain influence on the hydrotalcite nanoparticles.

[0096] Example 6: MgAl-LDH hydrotalcite nanoparticles prepared from divalent and trivalent metals in different molar ratios

[0097] (1) Disperse 10, 15, 20, 25 and 35 mmol of divalent metal salt MgCl2 in 25 mL of ultrapure water to obtain the corresponding divalent metal salt aqueous solution; disperse 5 mmol of AlCl3 in 25 mL of ultrapure water to obtain the corresponding trivalent metal salt aqueous solution.

[0098] (2) Mix 10, 15, 20, 25 and 35 mmol of MgCl2 solution with AlCl3 solution to obtain mixed salt solution, and disperse 30, 40, 50, 60 and 80 mmol of sodium hydroxide in 70 mL of ultrapure water; stir the mixed salt solution and sodium hydroxide in an ice water bath and continue stirring for 30 minutes, centrifuge at 4750g to remove supernatant, wash twice with ultrapure water, resuspend in 400 mL of ultrapure water and transfer to inner liner.

[0099] (3) The inner liner containing the LDH precursor product was preheated to 100°C and then kept warm in a conventional heat preservation device. After 6 hours of heat preservation, the inner liner was removed and cooled to room temperature to obtain MgAl-LDH hydrotalcite nanoparticles with different Mg / Al ratios.

[0100] The particle size distribution of hydrotalcite nanoparticles prepared with divalent and trivalent metals in different molar ratios was analyzed by DLS. Figure 11 As shown, the hydrotalcite synthesized with divalent and trivalent metals in molar ratios of 2:1, 3:1, 4:1, 5:1, and 7:1 exhibited uniform particle sizes of approximately 95±10 nm, 90±10 nm, 100±10 nm, 200±10 nm, and 130±20 nm, respectively. This demonstrates that hydrotalcite nanoparticles with different molar ratios of divalent and trivalent metals can be synthesized using conventional thermal insulation equipment.

[0101] Example 7: Hydrotalcite nanoparticles containing different divalent metal ions

[0102] (1) Disperse 10 mmol of divalent metal salts MgCl2, NiCl2, CoCl2 and ZnCl2 in 25 mL of ultrapure water to obtain the corresponding divalent metal salt aqueous solutions; disperse 5 mmol of AlCl3 in 25 mL of ultrapure water to obtain the corresponding trivalent metal salt aqueous solutions;

[0103] (2) The divalent metal salts MgCl2, NiCl2, CoCl2 and ZnCl2 were mixed with AlCl3 respectively; 30 mmol of sodium hydroxide was dispersed in 70 mL of ultrapure water; the mixed salt solution and sodium hydroxide were stirred and mixed in an ice-water bath under nitrogen protection and stirred for 30 minutes. The supernatant was removed by centrifugation at 4750 g, and then washed twice with ultrapure water and resuspended in 400 mL of ultrapure water to obtain a hydrotalcite precursor with a concentration of about 2 mg / mL, which was then transferred to the inner liner.

[0104] (3) Preheat the inner liner containing the LDH precursor product suspension to 100°C.

[0105] (4) The preheated inner liner was placed in a conventional heat preservation device and sealed for heat preservation. After heat preservation for 6 hours, the inner liner was removed and cooled to room temperature to obtain hydrotalcite nanoparticles containing different divalent metal ions.

[0106] The particle size distribution of hydrotalcite nanoparticles under different divalent metal salt conditions was analyzed by DLS. For example... Figure 12 As shown, the synthesized MgAl-LDH, NiAl-LDH, CoAl-LDH, and ZnAl-LDH hydrotalcites have uniform particle sizes, approximately 95±5 nm, 90±10 nm, 90±10 nm, and 200±10 nm, respectively. This indicates that hydrotalcite nanoparticles containing different divalent metal ions can be synthesized using conventional heat-insulating equipment.

[0107] Example 8: Hydrotalcite nanoparticles containing two divalent metal ions

[0108] (1) 10 mmol of divalent metal salt MgCl2 was dispersed in 25 mL of ultrapure water with 5 mmol of CuCl2, ZnCl2 and CoCl2 respectively to obtain the corresponding mixed divalent metal salt aqueous solution; 5 mmol of AlCl3 was dispersed in 25 mL of ultrapure water to obtain the corresponding trivalent metal salt aqueous solution; then they were mixed to obtain a mixed salt solution; 40 mmol of sodium hydroxide was dispersed in 70 mL of ultrapure water; the mixed salt solution and sodium hydroxide were stirred in an ice water bath and stirred for 30 minutes. After washing twice with ultrapure water, the mixture was centrifuged at 4750g and resuspended in 400 mL of ultrapure water to obtain a suspension of hydrotalcite precursor product with a concentration of about 2 mg / mL, and then transferred to the inner liner.

[0109] (2) The inner liner containing the LDH precursor product suspension was preheated to 100°C and then placed in a conventional heat preservation device for sealing and heat preservation. After heat preservation for 6 hours, the inner liner was removed and cooled to room temperature to obtain different types of hydrotalcite nanoparticles.

[0110] The particle size distribution of hydrotalcite nanoparticles under mixed divalent metal salt conditions was analyzed by DLS. For example... Figure 13 As shown, the average particle sizes of the synthesized CuMg2Al-LDH, ZnMg2Al-LDH, and CoMg2Al-LDH hydrotalcites are approximately 170±10 nm, 90±10 nm, and 80±10 nm, respectively. Figure 14 As shown, the synthesized CuMg2Al-LDH, ZnMg2Al-LDH, and CoMg2Al-LDH hydrotalcites all exhibit a regular hexagonal structure in the TEM image. This indicates that hydrotalcite nanoparticles containing two different divalent metal ions can be synthesized using conventional heat-insulating equipment.

[0111] Example 9: Hydrotalcite nanoparticles containing two trivalent metal ions

[0112] (1) 15 mmol of divalent metal salt MgCl2 was dispersed in 25 mL of ultrapure water to obtain an aqueous solution of divalent metal salt; 4.5 mmol of AlCl3 and 0.5 mmol of CeCl3 were dispersed in 25 mL of ultrapure water to obtain a corresponding mixed aqueous solution of trivalent metal salt; then they were mixed to obtain a mixed salt solution; 40 mmol of sodium hydroxide was dispersed in 70 mL of ultrapure water; the mixed salt solution and sodium hydroxide were stirred and mixed evenly and stirred for 30 minutes in an ice-water bath. After washing twice with ultrapure water, the mixture was centrifuged at 4750 g and resuspended in 400 mL of ultrapure water to obtain a hydrotalcite precursor with a concentration of about 2 mg / mL, which was then transferred to the inner liner.

[0113] (2) The inner liner containing the LDH precursor product was preheated to 100°C, and then sealed and insulated in a conventional heat preservation device. After 6 hours of heat preservation, the inner liner was removed and cooled to room temperature to obtain Mg3Al. 0.9 Ce 0.1 -LDH hydrotalcite nanoparticles.

[0114] Mg3Al analysis by DLS 0.9 Ce 0.1 The particle size distribution of -LDH-based hydrotalcite nanoparticles. For example... Figure 15 As shown, the synthesized Mg3Al 0.9 Ce 0.1 The average particle size of -LDH hydrotalcite is approximately 120±10 nm. This indicates that hydrotalcite nanoparticles containing two trivalent metal ions can be synthesized using conventional heat preservation equipment.

[0115] Example 10: Hydrotalcite nanoparticles with different trivalent metal ions

[0116] (1) 15 mmol of divalent metal salt MgCl2 was dispersed in 25 mL of ultrapure water to obtain a divalent metal salt aqueous solution; 5 mmol of FeCl3 was dispersed in 25 mL of ultrapure water to obtain a corresponding mixed trivalent metal salt aqueous solution; then the mixture was carried out to obtain a mixed salt solution; 40 mmol of sodium hydroxide was dispersed in 70 mL of ultrapure water; the mixed salt solution and sodium hydroxide were stirred and mixed in an ice-water bath and stirred for 30 minutes. After washing twice with ultrapure water, the mixture was centrifuged at 4750 g and resuspended in 400 mL of ultrapure water to obtain a hydrotalcite precursor with a concentration of about 2 mg / mL, which was then transferred to the inner liner.

[0117] (2) The inner liner containing the LDH precursor product was preheated to 100°C and then placed in a conventional heat preservation device for sealing and heat preservation. After heat preservation for 6 hours, the inner liner was removed and cooled to room temperature to obtain Mg3Fe-LDH hydrotalcite nanoparticles.

[0118] like Figure 16As shown, the average particle size of the synthesized Mg3Fe-LDH hydrotalcite is approximately 120 ± 10 nm. This indicates that hydrotalcite nanoparticles under different trivalent metal salt conditions can be synthesized using conventional heat-insulating equipment.

[0119] Example 11:

[0120] This application provides embodiments of different types of drugs loaded with hydrotalcite nanoparticles, including antibiotics, anti-inflammatory drugs, anticancer drugs, nucleic acid drugs, and protein drugs.

[0121] Among them, antibiotics can include moxifloxacin, penicillin, sulfonamides, etc.; anti-inflammatory drugs can include ibuprofen, naproxen, diclofenac, etc.; anticancer drugs can include methotrexate, 5-fluorouracil, doxorubicin, etc.; nucleic acid drugs can include small interfering RNA, plasmid DNA (pDNA), CpG oligonucleotides, etc.; and protein drugs can include insulin, growth hormone, enzyme-active proteins, etc.

[0122] Comparative Example 1: Preparation of hydrotalcite nanoparticles using the conventional hydrothermal method

[0123] Comparative sample synthesis: According to the hydrothermal preparation method of hydrotalcite nanoparticles provided in PCT / AU2005 / 001948: MgCl2 and AlCl3 were dissolved and mixed evenly in deionized water at a certain molar ratio to prepare 10 mL of aqueous solutions with magnesium ion concentrations of 0.6 mol / L and aluminum ion concentrations of 0.2 mol / L. A certain amount of NaOH was weighed and dissolved in distilled water to prepare 40 mL of 0.40 mol / L NaOH aqueous solution. 40 mL of NaOH aqueous solution was pre-placed in a flask and stirred at high speed using a magnetic stirrer. Then, the MgCl2 and AlCl3 solutions were quickly added to the NaOH aqueous solution, and the mixture was stirred at room temperature for 30 minutes. The suspension was collected, and the precipitate was collected using centrifugation at 4750 g and washed twice with ultrapure water. The precipitate was collected and evenly dispersed in water to form a suspension, thus obtaining the Mg3Al-LDH hydrotalcite precursor. Subsequently, a certain amount of Mg3Al-LDH precursor was placed in a high-pressure reactor and hydrothermally heated in a 100℃ constant temperature oven for 6 hours to obtain Mg3Al-LDH nanoparticles.

[0124] The morphology of Mg3Al-LDH nanoparticles prepared according to the above method was observed by transmission electron microscopy, and the results are shown in the figure. Figure 2 .from Figure 2 It can be seen that the obtained Mg3Al-LDH nanoparticles have a hexagonal layered structure and a size of about 100 nm.

[0125] This application proposes a novel hydrothermal synthesis strategy based on conventional heat-insulating equipment, significantly overcoming the limitations of traditional hydrothermal synthesis methods. Without the need for high-pressure reactors and precise temperature control equipment, nanoscale hydrotalcite nanoparticles can be prepared using readily available heat-insulating equipment (including but not limited to household slow cookers, thermostatic pots, and insulated boxes). This is achieved by preheating the hydrotalcite precursor product suspension to a specific temperature and then holding it in the heat-insulating device for a period of time. Experiments show that the obtained product retains its hexagonal plate-like morphology (particle size 20-1000 nm) and high crystallinity, with performance comparable to products from traditional hydrothermal methods. Furthermore, compared to traditional hydrothermal methods, since the cost and safety issues associated with scaling up high-pressure reactors are not considered, this application can easily achieve small- to medium-scale preparation of hydrotalcite nanoparticles in a volume range of 0.001-50 L and a concentration range of 0.01-100 mg / mL. The core innovation of this application lies in the application of readily available and low-cost thermal insulation equipment for the high-quality and controllable preparation of small to medium-sized hydrotalcite nanoparticles. It features low cost, simple operation, controllable quality, and adjustable scale, providing key technologies for the industrial preparation of high-quality hydrotalcite nanoparticles.

Claims

1. A method of preparing a suspension of particles of a layered double hydroxide, characterized in that, The application relates to a method for preparing a layered double hydroxide (LDH) suspension, comprising: placing a solution containing a layered double hydroxide precursor into a heat-retaining device for heat-locking treatment, so as to obtain a suspension of the layered double hydroxide particles; the heat-locking treatment is to maintain the temperature only by the heat-retaining device under normal pressure.

2. The method of claim 1, wherein, The solution containing the layered double hydroxide precursor is maintained at a temperature of 30-100 DEG C in the heat-retaining device; Optionally, the layered double hydroxide precursor is maintained at a temperature of 50-80 DEG C in the heat-retaining device; Optionally, after the solution containing the layered double hydroxide precursor is placed into the heat-retaining device, no external continuous heating and / or pressurization is needed; Optionally, the time for the heat-locking treatment is greater than or equal to 1 hour; Optionally, the time for the heat-locking treatment is 1-16 hours.

3. The method of claim 1, wherein, The solution containing the layered double hydroxide precursor is transferred into a pre-heatable container, the pre-heatable container containing the layered double hydroxide precursor is pre-heated to a target temperature, and a heat-retaining reaction is carried out, so as to obtain the suspension of the layered double hydroxide particles; Optionally, the pre-heatable container is a separate container matched with the heat-retaining device; Optionally, the heat-retaining device comprises an insulating shell for maintaining the temperature in the pre-heatable container.

4. The method of claim 1, wherein, Raw materials for preparing the layered double hydroxide precursor comprise mixed metal ions; Optionally, the mixed metal ions comprise divalent metal ions and trivalent metal ions; Optionally, the divalent metal ions comprise at least one of Mg 2+ , Zn 2+ , Cu 2+ , Co 2+ , Ni 2+ . Optionally, the trivalent metal ion comprises at least one of Al 3+ , Fe 3+ , and Ce 3+ . Optionally, the molar ratio of the divalent metal ions to the trivalent metal ions is 1:1-10:1; Optionally, the raw materials for preparing the layered double hydroxide precursor further comprise a basic compound; Optionally, the basic compound comprises at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate and ammonia; Optionally, the molar ratio of the basic compound to the mixed metal ions is 1.5:1-10:1; Optionally, after the basic compound and the mixed metal ions are mixed, the mixture is reacted in an environment with a temperature of 0-50 DEG C, so as to prepare the layered double hydroxide precursor; Optionally, after the basic compound and the mixed metal ions are mixed, the container containing the mixture is placed into an ice-water bath for reaction, so as to prepare the layered double hydroxide precursor.

5. The method of claim 1, wherein, The method for preparing the layered double hydroxide precursor comprises: preparing a layered double hydroxide precipitate by co-precipitation, so as to form a mixture of the layered double hydroxide precipitate and a solution containing a layered double hydroxide precursor; Optionally, the contact time of the layered double hydroxide precipitate and the solution is not more than 30 minutes; Optionally, the temperature of the co-precipitation reaction is less than or equal to 50 DEG C; Optionally, further comprising separating the layered double hydroxide precipitate from the solution; Optionally, further comprising washing the layered double hydroxide precipitate; Optionally, further comprising mixing the washed layered double hydroxide precipitate with a solvent, so as to prepare the solution containing the layered double hydroxide precursor; Optionally, the solvent in the solution containing the layered double hydroxide precursor comprises at least one of water, methanol, ethanol and an electrolyte solution; Optionally, the solution is a solution obtained by mixing a solution containing mixed metal ions and a solution containing a basic compound, and the reaction of the solution obtains a precipitate, which is the layered double hydroxide precursor. Optionally, the solvent in each of the solution containing mixed metal ions, the solution containing a basic compound independently comprises at least one of water, methanol, ethanol, an electrolyte solution.

6. A suspension of layered double hydroxide particles prepared according to the method of any one of claims 1 to 5.

7. A drug delivery system comprising the suspension of layered double hydroxide particles of claim 6.

8. A medicament comprising the suspension of layered double hydroxide particles of claim 6 or the drug delivery system of claim 7.

9. A vaccine comprising the suspension of layered double hydroxide particles of claim 6.

10. A catalyst comprising the suspension of layered double hydroxide particles of claim 6.

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