Methods for preparing reversible thermo-induced nanoemulsion in the absence of surfactants

Abstract

The invention provides a method for preparing a reversible thermally induced nano-emulsion under the condition of no addition of a surfactant. The method is based on a two-phase liquid system comprising a first liquid phase and a second liquid phase which are immiscible, and the vapor of the first liquid phase is dissolved in the second liquid phase by heating to a temperature sufficient to vaporize the first liquid phase to form a homogeneous mixture; the system is then cooled to a temperature below the saturation point of the first liquid phase in the second liquid phase, thereby inducing nucleation of the first liquid phase in the second liquid phase to form nanodroplets, resulting in a thermally induced nanoemulsion. The nano-emulsion can be decomposed and recovered into an original two-phase liquid system when being heated again, the reversible and controllable nano-emulsion preparation method is achieved through repeated heating-cooling steps, and the preparation method is suitable for various thermal response type intelligent conveying systems and other application scenes.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202510829283.9 (22) Application Date 2025.06.19 (30) Priority Data 63 / 675,251 2024.07.24 US (71) Applicant City University of Hong Kong Address Tat Chee Road, Kowloon, Hong Kong, China Applicant Hong Kong Polytechnic University (72) Inventors Zhu Pingan Wang Liqiu (74) Patent Agency Shenzhen Yibao Intellectual Property Agency (General Partnership) 44588 Patent Attorney Wang Qin Cao Yucun (51) Int.Cl. A61K 8 / 92 (2006.01) A61K 8 / 891 (2006.01) A61K 8 / 31 (2006.01) A61K 8 / 06 (2006.01) A61Q 19 / 00(2006.01) A61K 9 / 107(2006.01) A61K 47 / 44(2017.01) A61K 47 / 34(2017.01) A61K 47 / 06(2006.01) E06B 3 / 67(2006.01) A23L 29 / 00(2016.01) A23P 10 / 30(2016.01) C02F 1 / 00(2023.01) C09K 8 / 58(2006.01) C02F 101 / 30(2006.01) (54) Invention Title: Method for Preparing Reversible Thermally Induced Nanoemulsions Without Added Surfactants (57) Abstract: This invention provides a method for preparing reversible thermally induced nanoemulsions without added surfactants. The method is based on a two-phase liquid system comprising an immiscible first liquid phase and a second liquid phase. The system is heated to a temperature sufficient to vaporize the first liquid phase, causing its vapor to dissolve in the second liquid phase to form a homogeneous mixture. Subsequently, the system is cooled to a temperature below the saturation point of the first liquid phase in the second liquid phase, thereby inducing the first liquid phase to nucleate and form nanodroplets in the second liquid phase, generating a thermally induced nanoemulsion. This nanoemulsion can decompose and revert to the original two-phase liquid system upon reheating. Through repeated heating-cooling steps, a reversible and controllable nanoemulsion preparation method is achieved, suitable for various applications such as thermally responsive intelligent delivery systems. Claims 1 page, Description 11 pages, Drawings 18 pages, CN 121401164 A 2026.01.27 CN 1 21 40 11 64 A 1. A method for preparing a reversible thermally induced nanoemulsion under conditions without adding surfactants, characterized in that it comprises: providing a two-phase liquid system comprising a first liquid phase and a second liquid phase, wherein the first and second liquid phases are immiscible;The two-phase liquid system is heated to a temperature that vaporizes the first liquid phase, causing the first liquid phase vapor to dissolve into the second liquid phase to form a homogeneous mixture; and the two-phase liquid system is cooled to a temperature below the saturation point of the first liquid phase vapor in the second liquid phase, thereby inducing the first liquid phase vapor to nucleate into nanodroplets in the second liquid phase, forming a reversible thermally induced nanoemulsion; wherein the reversible thermally induced nanoemulsion decomposes into the two-phase liquid system upon reheating, and the reversible thermally induced nanoemulsion is formed again by repeating the above steps. 2. The method according to claim 1, wherein the volume ratio of the first liquid phase to the second liquid phase is 0.01:1 to 100:1. 3. The method according to claim 1, wherein the first liquid phase comprises water, and the second liquid phase comprises an oil selected from soybean oil, silicone oil, paraffin oil, hexadecane, toluene, and dichloromethane. 4. The method according to claim 1, wherein the reversible thermally induced nanoemulsion comprises water-in-oil (W / O) and oil-in-water (O / W) nanoemulsions. 5. The method of claim 1, wherein the reversible thermally induced nanoemulsion has nanodroplets with an average diameter of 25-1000 nm. 6. The method of claim 1, further comprising: controlling the size of the nanodroplets by adjusting the heating temperature and cooling rate. 7. The method of claim 1, wherein, in the cooling step, the temperature of the first liquid phase is lower than the temperature of the second liquid phase. 8. The method of claim 1, wherein the heating temperature of the two-phase liquid system is lower than the boiling points of the first and second liquid phases, and the cooling temperature is between 10°C and 40°C. 9. The method of claim 1, wherein the vapor formed in the first liquid phase during heating reaches a supersaturated state in the second liquid phase, and condenses and nucleates near the first-liquid-second-liquid phase interface during the cooling process. Claims 1 / 1 page 2 CN 121401164 A Method for preparing reversible thermally induced nanoemulsions without the addition of surfactants Technical Field

[0001] This invention relates to the field of nanotechnology, particularly the field of nanoemulsion technology. More specifically, this invention relates to a method for preparing stable and controllable nanoemulsions by cyclic heat treatment without the use of surfactants. Background Art

[0002] Emulsions are complex multiphase systems in which discrete droplets of one liquid are dispersed in another immiscible liquid, and their structure is usually stabilized by surfactants or amphiphilic molecules. Based on the average diameter of the droplets, emulsions are generally classified into macroemulsions (droplet size > 1 micrometer), nanoemulsions (droplet size approximately 20-200 nanometers), and microemulsions (droplet size approximately 10 nanometers or smaller). Among these types, nanoemulsions are gaining increasing attention due to their scale, which lies between the macroscopic and microscopic levels.Nanoemulsions have attracted much attention because they combine the high kinetic stability and low turbidity of microemulsions with the compositional flexibility of macroemulsions. Their small droplet size minimizes gravitational separation and droplet coalescence, thereby improving kinetic stability and enhancing optical transparency.

[0003] Therefore, nanoemulsions have been widely used in many fields, such as cosmetics, food technology, pharmaceuticals, agrochemicals, oil extraction, drug delivery systems, and the synthesis of template materials. Their ability to encapsulate and deliver hydrophilic and hydrophobic compounds enhances absorption and bioavailability, highlighting their functional diversity. However, although nanoemulsions are kinetically stable, they are inherently unstable from a thermodynamic perspective because they tend to form a two-phase separation state over time, i.e., forming two immiscible solutions with two volumetric phases.

[0004] The decomposition process of nanoemulsions follows a first-order rate law, i.e., the rate is exponentially related to exp(-ΔE / kBT), where ΔE is the energy barrier, kBT is the Boltzmann constant, and T is the temperature. This kinetic relationship reveals that nanoemulsions are extremely sensitive to temperature fluctuations. In particular, high temperatures significantly accelerate droplet coalescence, Ostwald ripening, and other destabilization processes, thereby limiting the actual shelf life and performance of nanoemulsions in high-temperature environments. This poses a significant challenge to industries that require thermal stress, such as food processing, pharmaceutical manufacturing, and cosmetic formulation.

[0005] To address this limitation, this invention provides a thermally induced nanoemulsification (TINE) strategy to reversibly switch between the formation and decomposition states of nanoemulsions. This method utilizes temperature as a controllable external stimulus to dynamically control the emulsion state. Compared to traditional emulsions that undergo irreversible decomposition upon heating, the TINE system allows nanoemulsions to be regenerated after cooling, even after decomposition under heating, providing a reusable and responsive emulsification method. This not only improves the heat resistance and operational flexibility of nanoemulsions but also offers new possibilities for building intelligent and adaptive delivery platforms in dynamic thermal environments.

[0006] The object of the present invention is to provide a material or method to solve the above-mentioned technical problems.

[0007] According to a first aspect of the present invention, a method for preparing a reversible thermally induced nanoemulsion under conditions without the addition of surfactants is provided, comprising the following steps: providing a two-phase liquid system comprising a first liquid phase and a second liquid phase, wherein the first and second liquid phases are immiscible; heating the two-phase liquid system to a temperature at which the first liquid phase vaporizes, thereby dissolving the first liquid phase vapor into the second liquid phase to form a homogeneous mixture; andThe two-phase liquid system is cooled to a temperature below the vapor saturation point of the first liquid phase in the second liquid phase, thereby inducing the vapor of the first liquid phase to nucleate into nanodroplets in the second liquid phase, forming a reversible thermally induced nanoemulsion.

[0008] According to an embodiment of the present invention, the reversible thermally induced nanoemulsion decomposes into the original two-phase liquid system upon reheating, and the above steps can be repeated to form a reversible thermally induced nanoemulsion again.

[0009] According to an embodiment of the present invention, the volume ratio of the first liquid phase to the second liquid phase is 0.01:1 to 100:1.

[0010] According to an embodiment of the present invention, the first liquid phase includes water, and the second liquid phase includes oil selected from soybean oil, silicone oil, paraffin oil, hexadecane, toluene, and dichloromethane.

[0011] According to an embodiment of the present invention, the reversible thermally induced nanoemulsion includes water-in-oil (W / O) and oil-in-water (O / W) nanoemulsions.

[0012] According to one embodiment of the present invention, the reversible thermally induced nanoemulsion has nanodroplets with an average diameter of 25-1000 nm.

[0013] According to one embodiment of the present invention, the size of the nanodroplets can be controlled by adjusting the heating temperature and cooling rate.

[0014] According to one embodiment of the present invention, in the cooling step, the temperature of the first liquid phase is lower than the temperature of the second liquid phase.

[0015] According to one embodiment of the present invention, the heating temperature of the two-phase liquid system is lower than the boiling points of the first liquid phase and the second liquid phase, and the cooling temperature is between 10°C and 40°C.

[0016] According to one embodiment of the present invention, the vapor formed in the first liquid phase during heating reaches a supersaturated state in the second liquid phase, and condenses and nucleates near the first liquid phase-second liquid phase interface during the cooling process.

[0017] Referring to the accompanying drawings, embodiments of the present invention will be described in more detail below, wherein:

[0018] Figures 1A-1D illustrate reversible nanoemulsification regulated by thermal induction, wherein Figure 1A is a schematic diagram illustrating the cyclic heating and cooling process of reversible nanoemulsification; Figure 1B shows an image of the reversible transition between emulsification and deemulsification using soybean oil (upper layer) and water (lower layer) as an example system, wherein the diameter of the glass bottle is 18 mm; Figure 1C is an optical photograph of nanodroplets under a microscope; Figure 1D shows the size distribution of nanodroplets measured by dynamic light scattering, wherein the polydispersity index is 0.003, indicating that the nanoemulsion is monodisperse;

[0019] Figure 2 illustrates the Tyndall effect in the nanoemulsion of the present invention;

[0020] Figures 3A-3H illustrate the thermal conditions for nanoemulsion formation, where Figure 3A shows a water-in-oil nanoemulsion in a glass container; Figure 3B shows a non-emulsified liquid in a polypropylene container; Figures 3C-3D show the temperature changes of the two-phase liquid systems in the glass container (Figure 3C) and the polypropylene container (Figure 3D) during air cooling, respectively, with insets showing the thermal distribution of the temperature.Imaging images; Figures 3E-3F show numerical simulations of the temperature distribution of a two-phase liquid system in a glass container (Figure 3E) and a polypropylene container (Figure 3F) during air cooling; Figure 3G is a schematic diagram of nanodroplet nucleation at the water-oil interface promoted by thermocapillary waves; Figure 3H shows an image of water-in-oil emulsion formation during cooling in a cold water bath, where the dashed arrows indicate the direction of internal flow.

[0021] Figures 4A-4B show the cooling of the water-oil system in the polymer container. Figure 4A shows the temperature change of water and oil over time when the system is cooled in a cold water bath. The oil temperature is initially lower than the water temperature, but after about 150 seconds of cooling, the oil temperature begins to exceed the water temperature. Figure 4B shows an image of the water-oil system. When the system is cooled in water (far right), an oil-in-water nanoemulsion forms. When cooled in air (middle), no nanoemulsion forms. The far left shows untreated water and oil (immiscible).

[0022] Figures 5A-5B show temperature distribution diagrams depicted by numerical simulation. These are snapshots of the temperature distribution when the water-oil system is placed in a glass container (Figure 5A) or a polymer tube (Figure 5B), heated to 90°C, and then cooled in a cold water bath. It can be seen that the highest temperature is located in the upper oil phase.

[0023] Figures 6A-6D show the temperature change over time as depicted by numerical simulation, including the upper oil phase, the intermediate water-oil interface, and the lower water phase during the cooling process. Figure 6A shows the product placed in a glass container and cooled in air; Figure 6B shows the product placed in a polymer container and cooled in air; Figure 6C shows the product placed in a glass container and cooled in a cold water bath; Figure 6D shows the product placed in a polymer container and cooled in a cold water bath. It is noteworthy that nanoemulsification occurs in Figures 6A, 6C, and 6D, and the oil temperature is greater than the water-oil interface temperature To > Ti, while no nanoemulsification occurs in Figure 6B, and the oil temperature is less than the water-oil interface temperature To < Ti.

[0024] Figures 7A-7C illustrate the mechanism of thermally induced nanoemulsification. Figure 7A shows images of nanoemulsions with different turbidity at different heating temperatures; Figure 7B shows the relationship between the mass fraction of nanodroplets and the heating temperature; Figure 7C shows the relationship between nucleation temperature and heating temperature.

[0025] Figures 8A-8C illustrate the mechanism for controlling the size of nanodroplets, where Figures 8A-8B show the correlation between nanodroplet size and heating temperature when the two-phase liquid system is cooled in air (Figure 8A) and in a cold water bath (Figure 8B), respectively; Figure 8C shows the effect of water phase volume on nanodroplet size with an oil phase volume of 3 mL (two-phase liquid system cooled in air);

[0026] Figure 9 shows the trend of water temperature and oil temperature over time when the two-phase liquid system (placed in a glass container and first heated to 90°C) is cooled in water.

[0027] Figures 10A-10E illustrate the characteristics of thermally induced nanoemulsions, wherein Figure 10A shows images of oil-in-water emulsions prepared using different two-phase liquid systems; Figure 10B shows water-in-oil and oil-in-water nanoemulsions; Figure 10C shows nanoemulsions prepared using a high-viscosity silicone oil-water system; Figure 10D shows the scale of nanoemulsion preparation and long-term stability (the nanoemulsion prepared using a soybean oil-water system remained stable after 16 months); Figure 10E shows a radar chart comparing the advantages and disadvantages of the thermally induced nanoemulsions of the present invention with other nanoemulsion methods; and

[0028] Figures 11A-11B show the addition of 1% sorbitan oleate (Span 80) as a surfactant in a soybean oil-water system to generate water-in-oil nanoemulsions, wherein Figure 11A shows images of the water-in-oil nanoemulsions at 1 week and 6 weeks after preparation, showing that the emulsion has good stability; Figure 11B shows the correlation between nanodroplet size and heating temperature. Detailed Description

[0029] In the following description, a method for preparing reversible thermally induced nanoemulsions without the addition of surfactants is listed as a preferred embodiment. It will be apparent to those skilled in the art that modifications, including additions and / or substitutions, can be made without departing from the scope and spirit of the invention. Specific details may be omitted below to avoid obscuring the invention; however, this document is written to enable those skilled in the art to practice the technical content disclosed herein without excessive experimentation.

[0030] As used herein, the term “reversible” refers to the ability of a nanoemulsion system to undergo a phase transition between a dispersed nanodroplet state (emulsified) and a bulk two-phase state (non-emulsified) through an externally applied thermal cycle (particularly heating and cooling) without the addition or removal of chemical reagents such as surfactants or cosolvents. Upon heating, the nanodroplets dissolve into a continuous phase, forming a transparent or non-turbid blocky liquid; upon cooling, the dispersed nanodroplet phase spontaneously reforms due to condensation and nucleation phenomena that occur as the temperature decreases. This transformation can be repeated multiple times without permanently losing the ability to form emulsions or significantly reducing droplet size distribution or stability.

[0031] Based on the phenomenon of atmospheric cloud formation in nature, this invention provides a reversible emulsification method. When moist air rises, cools, and reaches a supersaturated state, suspended water droplets or ice crystals begin to appear in the clouds, triggering nucleation condensation of dust or salt particles in the air. This dynamic process demonstrates that a reversible transition between the dispersed phase and the bulk liquid phase can be achieved by controlling the condensation and evaporation caused by temperature fluctuations.

[0032] Based on this equilibrium-driven mechanism, this invention provides a thermally induced nanoemulsification method for the reversible formation and decomposition of nanoemulsions in a two-phase liquid system. This method coordinates the cyclic heating and cooling of two immiscible liquid phases (such as water and oil).However, it simulates cloud dynamics to produce nanodroplets without the use of surfactants. More specifically, the reversible method is that when the system is heated, one liquid (such as water) evaporates and dissolves into another liquid (such as oil) to form a homogeneous solution; upon cooling, the vapor condenses, resulting in the formation of nanodroplets in the continuous phase. This process is completely reversible, meaning that reheating the system decomposes the nanodroplets, causing them to dissolve again, thus allowing for repeated emulsification-dissolution cycles.

[0033] Compared with traditional emulsification techniques, the thermally induced nanoemulsification method has several advantages. First, this invention provides a surfactant-free method for producing nanoemulsions, avoiding the environmental and health problems associated with surfactants; second, since this method relies only on simple thermal cycling, it is suitable for low-cost, large-scale applications; third, this method allows for reversible fine-tuning control of droplet size and emulsion, thereby enhancing the function of dynamic or responsive formulations.

[0034] The nanoemulsion system of the present invention can switch between emulsified and non-emulsified states, enabling the prepared nanoemulsion to be transported in a controlled manner, reused, and emulsified on demand. The resulting nanoemulsion is characterized by high stability, extended shelf life, precise droplet size distribution, and compatibility with various emulsion types and solvent systems. Therefore, the application fields of the present invention include, but are not limited to, food processing, pharmaceuticals, cosmetics, enhanced oil recovery, and smart materials. The reversibility of temperature provides a new dimension to nanoemulsions. The method of the present invention overcomes the limitations of traditional nanoemulsification methods, providing new functions and adaptability for nanoemulsion technology.

[0035] According to a first aspect of the present invention, a method for preparing reversible thermally induced nanoemulsions under conditions without added surfactants is provided. This method achieves the reversible formation of nanoemulsions without the participation of surfactants by controlling the interaction and thermodynamic behavior between the liquid phases.

[0036] More specifically, firstly, a two-phase liquid system is provided, comprising a first liquid phase and a second liquid phase, wherein the two liquid phases are immiscible. In some embodiments, the first liquid phase may be water, and the second liquid phase may be an oily liquid, such as any one or a combination of soybean oil, silicone oil, paraffin oil, hexadecane, toluene, or dichloromethane. The mass percentages of the first liquid phase and the second liquid phase can be set according to specific needs, for example, in the range of 0.01:1 to 100:1.

[0037] In one embodiment, the volume ratio of the first liquid phase to the second liquid phase is 1:1.

[0038] During operation, the above-mentioned two-phase liquid system is first heated to a temperature range sufficient to vaporize the first liquid phase, for example, heated to between 60°C and 150°C. Due to the vaporization of the first liquid phase, the vapor produced will partially dissolve into the second liquid phase, making the second liquid phase contain supersaturated first liquid phase vapor, forming a temporarily homogeneous mixed system.

[0039] Next, the system is rapidly or at a controlled rate cooled to a temperature below the vapor saturation point of the first liquid phase in the second liquid phase, for example, to between 10°C and 40°C. During this process, due to the cooling of the supersaturated vapor, the first liquid phase spontaneously nucleates in the second liquid phase, forming a nanoscale droplet dispersion system, thereby generating a thermally induced nanoemulsion. The formed emulsion can be oil-in-water or water-in-oil, depending on the type of liquid phase used and its volume distribution. The particle size range of the nanodroplets is typically between 25 nm and 1000 nm, and can be adjusted by controlling the heating temperature and cooling rate.

[0040] In one embodiment, during the above cooling process, the temperature of the first liquid phase is lower than the temperature of the second liquid phase to enhance the nucleation effect.

[0041] It is worth noting that this thermally induced emulsion system is reversible: when the formed nanoemulsion is reheated to a high temperature (e.g., 60°C to 150°C), the emulsion will re-separate into the original two-phase liquid system, and by repeating the above heating-cooling steps, the nanoemulsion can be formed again, showing good reversibility and cycle stability.

[0042] In addition, the vapor formed in the first liquid phase during heating can reach a supersaturated state after entering the second liquid phase, and during cooling, the vapor will condense and nucleate near the interface between the first and second liquid phases, forming dispersed nanodroplets. This mechanism is the key to emulsion formation, without relying on any traditional surfactants to stabilize the system.

[0043] In summary, the present invention provides a reversible and controllable method for preparing thermally induced nanoemulsions without the addition of surfactants, which has the advantages of simple process, strong repeatability, and wide applicability, and is applicable to multiple technical fields such as chemical engineering, drug delivery, cosmetics, and food industry.

[0044] Examples

[0045] Example 1: Preparation of Reversible Thermally Induced Nanoemulsions

[0046] This invention achieves a dynamic balance between vapor dissolution and condensation through heating and cooling, allowing an immiscible two-phase liquid system to reversibly switch between forming nanoemulsions and decomposition (Figure 1A). In one embodiment, the first liquid phase and the second liquid phase are water and soybean oil, respectively (Figure 1B), with a volume ratio of 1:1. First, in preparing the reversible thermally induced nanoemulsion, the immiscible and stratified water and soybean oil are heated. As the temperature rises, water evaporates and permeates into the soybean oil via vapor until the water vapor in the soybean oil becomes supersaturated. Subsequently, a cooling step is performed to condense the water vapor in the soybean oil and form nano-sized water droplets dispersed in the oil phase (Figure 1C). It is worth noting that highly monodisperse water nanodroplets with a diameter of less than 100 nm (Figure 1D) can be generated by finely adjusting the heating and cooling parameters, for example, when the heating temperature is set to 90 degrees and the system is allowed to cool naturally in air.

[0047] Due to the presence of nano-water droplets, these mist-like water-in-oil (W / O) nanoemulsions exhibit the Tyndall effect (Figure 2). When the water-in-oil nanoemulsion is heated to a high temperature (Th), deemulsification occurs, causing the nano-droplets to dissolve and return to a transparent state. If cooled to a lower room temperature (Tc), vapor condensation can be triggered again, causing the system to re-emulsify and restore its turbid appearance, further demonstrating a reversible nanoemulsification method with repeatable heating-cooling cycles (Figure 1B). It is worth noting that no surfactants are required in the process; only a conventional two-liquid system is needed.

[0048] In one embodiment, the water-oil two-phase system is heated to a target temperature (Th) using a hot water bath. After heating, the two-phase liquid system is removed from the hot water bath and cooled by natural convection of air or cold water, during which nanoemulsification occurs. After cooling, the two-phase liquid system can be reheated by a hot water bath or hot plate to deemulsify the nanoemulsion.

[0049] The above preparation method is applicable to various water-oil systems, including paraffin oil / water systems, hexadecane / water systems, and silicone oil / water systems (Figure 10A), as well as various other immiscible water-oil combinations. Since oil has lower volatility than water, water vapor condensation in the oil dominates, leading to the formation of water-in-oil (W / O) nanoemulsions (Figure 10A). Based on the volatility characteristics of oil, the method of the present invention can also be used to prepare oil-in-water (O / W) nanoemulsions, because during cooling, water vapor condensation in the oil and oil vapor condensation in the water can occur simultaneously, as shown in toluene / water and dichloromethane (DCM) / water systems (Figure 10B). Furthermore, the method of the present invention is not limited by the viscosity of the liquid used; as shown in Figure 10C, water-in-oil nanoemulsions can be successfully produced even using silicone oil with a viscosity of 3000 cSt. Furthermore, it is worth noting that by increasing the size of the reaction vessel, large-scale mass production of nanoemulsions can be achieved using the method of the present invention, and the resulting emulsion can maintain stability for more than one year without the need for surfactants (Figure 10D).

[0050] Compared with existing nanoemulsion methods, the method of the present invention has several unique advantages. First, it is a low-energy-consumption method, requiring mainly the heat absorbed by the water-oil system during heating, with the thermal energy equation being (c_water Φ_water + c_oil Φ_oil)(Th-Tc), where c represents the specific heat capacity, Φ represents the mass fraction of the liquid, and Φ_water and Φ_oil add up to 1. This energy consumption is approximately 104-105 J kg⁻¹, depending on the thermal properties of the material, and there are no restrictions on the mode or duration of energy input. Therefore, nanoemulsions can be produced more flexibly, multifunctionally, and scalably. In some embodiments of the present invention,The cooling time is typically around 10-10³ seconds, so the power consumption of the reaction is approximately 10-10³ W kg⁻¹, far lower than the reported values ​​of other low-energy methods (10³-10⁵ W kg⁻¹). Furthermore, the method of this invention can utilize low-grade waste heat generated by various heat-generating reactions or devices (such as power plants, automobile engines, air conditioners, electronics, and geothermal energy) as a heat source for the preparation of nanoemulsions.

[0051] Additionally, as described above, the method of this invention includes the use of surfactants. The preparation of nanoemulsions in this invention is accomplished entirely by controlling thermal conditions, without the need for surfactants. While surfactants can improve the energy barrier and thus effectively stabilize nanoemulsions, they also bring many disadvantages, such as environmental impact, potential health problems, biodegradability issues, interference with natural processes, and cost impacts. Therefore, this invention also eliminates these concerns. Furthermore, even without any surfactants, the nanoemulsions prepared by this invention exhibit good stability, and through a reversible emulsification method, if the nanoemulsion becomes unstable, the heating-cooling steps can be repeated to extend the stability and lifespan of the nanoemulsion.

[0052] In another embodiment, the method of the present invention is also applicable to two-phase liquid systems with added surfactants (Figures 11A-11B).

[0053] Therefore, the method of the present invention provides a multifunctional method for preparing nanoemulsions, applicable to a variety of materials, such as water, vegetable oils, hydrocarbons, silicone oils, volatile organic reagents, and high-viscosity liquids. Furthermore, it is also applicable to the preparation of oil-in-water and water-in-oil nanoemulsions, demonstrating its versatility in emulsion types. Therefore, the method of the present invention also has many advantages, such as: long-term stability, no added surfactants, low energy consumption, large-scale production, precise control of droplet size, and versatility in emulsion types and material systems.

[0054] Example 2, Relevant Parameters of Nanoemulsion

[0055] The cooling process plays an important role in the preparation of nanoemulsions. In order to detect the temperature distribution of the water / oil dual-phase liquid system during the cooling process, four cases were simulated: (1) a water / oil dual-phase liquid system in a glass container and cooled in air; (2) a water / oil dual-phase liquid system in a polypropylene container and cooled in air; (3) a water / oil dual-phase liquid system in a glass container and cooled in a cold water bath; and (4) a water / oil dual-phase liquid system in a polypropylene container and cooled in a cold water bath. During heating, the dual-phase liquid system in the container is directly heated by heat conduction, while during cooling, natural convection occurs from the fluid outside the container (such as air or water). In this embodiment, the system is cooled from 90°C to room temperature 25°C.

[0056] When cooling the heated dual-phase liquid system (high temperature Th) in a room temperature environment (room temperature Tc), when the dual-phase liquid systemWhen placed in a glass container, the formation of a heat-induced nanoemulsion can be observed (Fig. 3A); conversely, when the two-phase liquid system is in a polypropylene container and cooled to room temperature, the formation of a nanoemulsion does not occur (Fig. 3B). This difference shows that the formation of a nanoemulsion depends on the temperature distribution within the two liquid phases, and the temperature distribution of the two phases is affected by the thermal properties of the container material.

[0057] This view can be further confirmed by detecting the temperatures of the water and oil phases: when nanoemulsification occurs, the temperature of the water is lower than that of the oil (Fig. 3C), while when emulsification fails, the temperature of the water is higher than that of the oil (Fig. 3D). To further verify this, a cooling test was conducted using a polymer container as the reaction vessel, and the cooling process was accelerated by rapidly immersing the container in cold water. At this time, a nanoemulsion was successfully generated (Fig. 4), and after measurement, the temperature of the water phase in the later cooling stage was lower than that of the oil phase (Fig. 4A). This result is consistent with the result in Fig. 3C and contrasts with the phenomenon in Fig. 3D.

[0058] Numerical simulations further illustrate the non-uniform temperature distribution within the two-phase system. As shown in Figures 3E-3F, 5, and 6, the location of the highest temperature varies depending on the cooling settings and conditions. These results show that the lower water phase is more sensitive to changes in cooling conditions compared to the upper oil phase. When the water cools faster than the oil, the hottest area shifts to the upper oil layer, regardless of whether a container with higher thermal conductivity (such as glass) or a more efficient cooling medium (such as cold water instead of air) is used. This creates a thermal gradient where oil temperature > temperature at the water-oil interface > water temperature (Figure 6), a condition conducive to the formation of nanoemulsions.

[0059] During cooling, water vapor in the oil phase may become supersaturated. When the highest temperature is in the water phase (as shown in Figures 3D and 3F), condensation frequently occurs at the oil-air interface. Although water nanodroplets may nucleate in this region, they cannot form stably and are likely to evaporate rapidly into the surrounding air, resulting in poor or unstable nanoemulsion formation. In contrast, when the temperature of the upper oil layer is hotter than that of the lower water layer (as shown in Figures 3C and 3E), water vapor condenses near the lower-temperature water-oil interface (Figure 3G), which is conducive to the stable nucleation and formation of water nanodroplets. Once formed, these nanodroplets diffuse and leave the interface in a short time (within a few seconds) (Figure 3G), and then flow with the convection in the oil phase over a longer timescale (e.g., 10 seconds or more) (Figure 3H), which helps to stabilize the formation of the nanoemulsion.

[0060] Example 3, Mechanism of Nanoemulsion

[0061] In addition to cooling, the method of the present invention also shows high sensitivity to changes in heating temperature (Th). As shown in Figure 7A, the nanoemulsion only begins to form when Th exceeds a specific threshold Tt (50℃ < Tt < 60℃ in the experiment), and theThe turbidity of the nanoemulsion also increases with the increase of Th, because the higher the temperature, the higher the solubility of oil for water vapor. Therefore, at a higher heating temperature, more water vapor can dissolve in the oil, and more water vapor can condense in the oil phase to produce a nanoemulsion with a higher mass fraction of nanodroplets (Figure 7B). In the subsequent cooling process, the temperature of the water-oil interface (Ti) must be reduced below the critical value (Tic) to initiate water vapor nucleation for nanoemulsion production. Experiments show that the nucleation temperature Tic increases with the increase of the heating temperature Th (Figure 7C).

[0062] To further illustrate the dynamics of the heating temperature (Th) controlling the formation of nanoemulsions, it is assumed that the thermocapillary waves at the water-oil interface provide active sites conducive to the stable nucleation of nanodroplets, and the nucleation process depends on the relative values ​​of the critical nucleation radius (rc) and the thermal length (lt). For uniform nucleation, the critical nucleation radius is calculated using classical nucleation theory. The work (W) for nucleation and clustering is: W = -αn + βn² / 3, where α = kBTln(SR), γow is the water-oil interfacial tension, Vw is the volume of one molecule in the liquid phase, kB is the Boltzmann constant, T is the absolute temperature, SR = Pv / Psat is the supersaturation (Psat is the saturated vapor pressure on the plane, Pv is the actual vapor pressure on the spherical droplet), and n = V / vw is the number of molecules in the cluster (V is the volume of the cluster). In this embodiment, kB = 1.380649 × 10⁻²³ J / K and vw = 2.9885 × 10⁻²⁹ m³ / mol.

[0063] By setting r = (3nvw / 4π) 1 / 3, the required work can be maximized, and the critical nucleation radius (rc) can be obtained. When the radius is greater than this, stable nucleation can occur:

[0064] This relationship is the Ostwald-Freundlich form of the Kelvin equation. The corresponding maximum work gives the free energy barrier, as shown below: Specification 7 / 11 Page 9 CN 121401164 A

[0065] For smaller ΔP = Pv - Psat and ΔT = T - Tsat, it can be known from:

[0066] Empirical relationship:

[0067] Where Tsat is the saturation temperature. Assuming Tsat = Ti and T = Th, where Ti represents the temperature at the water-oil interface and Th represents the highest temperature during the heating stage, the critical nucleation radius rc can be estimated using the following formula:

[0068] The thermal length can characterize the roughness of the water-oil interface and is calculated from the balance between thermal energy and surface energy:

[0069] Comparing the thermal length (lt) with the critical nucleation radius (rc), it can be seen that the critical nucleation radius decreases as the interface temperature (Ti) increases. When the temperature is below the nucleation temperature (Tic), the critical nucleation radius will be smaller than the interface roughness, causing water molecules to...The clustering nucleation process is relatively stable thermodynamically, promoting the formation of nanodroplets. Using the empirical relationship rc≈2lt, the theoretical estimate of Tic is in agreement with the experimental results (Figure 7C), where, for the water-soybean oil interface without surfactant, γow = 22mN / m, vw = 2.9885×10-29m3 / mol, kB = 1.380649×10-2J / K. This theoretical framework also shows that when the nucleation temperature is 25℃ (room temperature), the maximum temperature of the heating stage needs to reach at least 56.8℃ (Figure 7C).

[0070] Example 4, Control of Nanodroplet Size

[0071] Thermal conditions significantly affect the size of nanodroplets. When the two-phase liquid system is cooled in air, the diameter of the water nanodroplets decreases with increasing heating temperature (Figure 8A), while when cooled in cold water, the droplet diameter remains relatively constant and does not change significantly with changes in heating temperature (Figure 8B). To further confirm the mechanism for regulating the size change of water nanodroplets, this invention proposes two different mechanisms: nucleation-limited growth and diffusion-limited growth of nanodroplets.

[0072] During a relatively slow cooling process (e.g., cooling in air), since the cooling time (tc) is much longer than the diffusion time (td), water nanodroplets are initially generated at the water-oil interface and then diffuse into the oil phase during the cooling process. Therefore, the nucleated droplets have enough time to diffuse from the lower temperature water-oil interface to the higher temperature oil phase, allowing nanodroplets to continue to be generated at the interface. The diffusion time is td ~ (10rd) 2 / D, where rd is the nanodroplet radius and D is the mass diffusion coefficient, which can be calculated using the Stokes-Einstein relation D = kBT / 6πηord, where ηo is the dynamic viscosity of the oil. Therefore, the generated water nanodroplets will leave the water-oil interface, promoting the potential nucleation of subsequent nanodroplet arrays, the number of which is approximately n ~ Awo / rd 2, where Awo represents the surface area of ​​the water-oil interface.

[0073] During the cooling process with a cooling time of tc, the total number of nucleation events (N) is estimated to be N ~ ntc / td. To ensure the conservation of water mass in the oil phase, the equation can be derived where ρ is the density of the liquid, is the mass fraction of water in the oil phase, Vo is the volume of oil, and the subscripts "w" and "o" represent water and oil, respectively. Therefore, if tc >> td, droplet formation is limited by the number of nucleation events N, and can be estimated by the following formula: Specification 8 / 11 pages 10 CN 121401164 A

[0074] This proportionality law shows that the droplet size decreases with the mass fraction of water in the oil phase. Assuming that it increases with increasing heating temperature (Th) (Figure 7B), the droplet size decreases with increasing heating temperature, consistent with the results in Figure 8A.

[0075] On the other hand, if the liquid is rapidly cooled via the lumped capacitance model, the cooling time tc is approximately tc ~ C / hA, where C represents the total heat capacity, h represents the heat transfer coefficient, and A is the heat transfer surface area. During the cooling process of the oil phase, tc can be obtained by fitting the exponential change of temperature over time, and the obtained tc is approximately 522 seconds (as shown in Figure 3C). Using all parameter conditions at room temperature (T = 298K), through the above equation (3), at a heating temperature of 90℃, the nanodroplet radius of the water nanodroplets formed in soybean oil is approximately 48nm, which is consistent with the result in Figure 8A. According to the predicted value of the nanodroplet radius, the diffusion time is approximately 3 seconds, which is significantly less than the cooling time (522 seconds), thus satisfying the conditions required in the nucleation-limited growth model.

[0076] For rapid cooling processes (such as cold water bath cooling with tc ≤ td), the generation of nanodroplets is mainly limited by the diffusion of water vapor in the oil. For example, during cooling in a cold water bath, the cooling time for a nanodroplet with a radius of approximately 125 nm is approximately 17 seconds (Fig. 9) and the diffusion time is approximately 51 seconds (Fig. 8B). In this case, due to the influence of water vapor diffusion in the oil, the nucleated nanodroplets will remain near the water-oil interface throughout the cooling process. The vapor concentration (c) in the oil phase can be estimated using the steady-state diffusion equation:

[0077] The Laplace equation described above can be expressed as follows:

[0078] Where A and B are constants to be determined, and r is the radial coordinate. At the droplet surface, the vapor concentration is c0, while at a distance from the droplet, the vapor concentration is c∞. The relevant boundary conditions are: c|r=∞=c∞

[0079] Here, r0 is the radius of the condensed droplet. Therefore, it can be known that A=c∞ and B=(c0-c∞)rd. Therefore, the vapor concentration can be expressed as

[0080] According to Fick's law, water vapor in the oil phase will propagate through diffusion, and the vapor flux J toward the droplet can be expressed as:

[0081] Wherein, Dv is the mass diffusion coefficient of water vapor in the oil, Dv=kBT / 6πηorv, where rv is the radius of the water molecule (rv=0.141nm). For the three-dimensional growth of spherical droplets, the droplet volume (V) is controlled by the following factors:

[0082] The expanded formula of the droplet radius can be derived as follows:

[0083] When T = 298K, Dv = 1.99 × 10⁻¹¹ m² / s, ρw = 1000 kg / m³, ηo = 57 mPa s, (c∞ - c0) is approximately 0.1 kg / m³, tc = 17 s, and the radius of the water nanodroplet calculated by equation (4) is approximately 184 nm, which is consistent with the droplet size in Figure 8B.

[0084] Through the two models mentioned above, it can be seen that the relevant parameters of the cooling process significantly affect the size of the nanodroplets. Therefore, the method of the present invention can effectively regulate the droplet size through precise thermal control. For example, both models show that the droplet size can be increased by extending the cooling time. As shown in Figure 8C, the droplet size also increases with the increase of water volume (keeping the oil volume constant). This is because when the water volume is high, the total heat capacity (C) increases, increasing the required cooling time.

[0085] In summary, the reversible thermally induced nanoemulsion preparation method of the present invention utilizes the reversible dissolution and condensation of steam through a heating-cooling cycle to achieve reversible nanoemulsion generation and decomposition, providing a reversible, simple, and large-scale method, while also possessing energy-saving and surfactant-free characteristics. The obtained nanoemulsion has advantages such as excellent stability, diverse types, and controllable droplet size. Through this novel thermal response system, its transparency also switches with the generation and decomposition of the nanoemulsion, whereas conventional liquids require the addition of corresponding stimulus-responsive materials to achieve this effect. Therefore, these emulsions can also be applied to thermochromic windows of buildings, providing high energy-saving performance and low cost.

[0086] More specifically, the present invention has the following advantages:

[0087] 1. Reversible emulsification

[0088] A nanoemulsion that can be repeatedly generated and decomposed is prepared by controlled heating and cooling cycles. During heating, the first liquid phase (water) evaporates and dissolves into the second liquid phase (oil), forming a homogeneous mixture; after cooling, water vapor condenses into nanodroplets in the oil phase. More particularly, the method of the present invention can control the droplet size of the nanoemulsion by fine-tuning the thermal conditions during the heating and cooling cycles, which is quite important for applications that require specific droplet sizes, such as drug delivery systems and template material synthesis.

[0089] 2. No Added Surfactants

[0090] Compared to traditional nanoemulsification techniques that require surfactants to stabilize the emulsion, the method of the present invention can successfully prepare nanoemulsions without adding any surfactants, eliminating the potential environmental and health problems caused by surfactants. In traditional nanoemulsification methods, surfactants are usually required to stabilize the emulsion. Although surfactants are effective, they may pose risks to the environment and health, including biodegradability and interference with nature. The method of the present invention can effectively eliminate these problems by producing highly stable nanoemulsions simply by controlling thermal conditions. This surfactant-free method reduces environmental impact and production costs while maintaining excellent emulsion stability.

[0091] 3. Energy Efficiency

[0092] The method of the present invention requires very little energy because it mainly involves heating only a two-phase liquid system. The energy consumption is mainly proportional to the thermal properties of the material, and most of it can be obtained from low-grade waste heat from other industries (e.g., power plants, automobile engines).The energy requirement is approximately 10-103 W kg⁻¹, which is much lower than other low-energy methods (typically between 103-105 W kg⁻¹).

[0093] 4. Large-scale production

[0094] The method of the present invention can be scaled up to produce nanoemulsions on a large scale. Large-scale production can be achieved by simply increasing the size of the reaction vessel without reducing the quality or stability of the nanoemulsion.

[0095] 5. Diversity of emulsion types

[0096] The method of the present invention can produce water-in-oil and oil-in-water nanoemulsions and is applicable to a variety of liquid combinations, including vegetable oils, hydrocarbons, silicone oils and volatile organic reagents, effectively broadening its industrial applications, such as pharmaceuticals, cosmetics, food and petroleum recycling. Instruction manual, pages 10 / 11, CN 121401164 A

[0097] 6. Long-term stability

[0098] The nanoemulsion prepared by the method of the present invention has excellent stability and can maintain its performance for a long time (e.g., more than one year) without the need for surfactants. Furthermore, it has reversible properties, thus the nanoemulsion can be regenerated through continuous heating and cooling cycles, which not only extends the emulsion's lifespan but also endows it with reusable and modifiable properties.

[0099] The present invention is applicable to a variety of fields, including but not limited to:

[0100] Cosmetics: It can prepare fine, stable nanoemulsions suitable for cosmetics, improving the texture, absorption, and delivery of active ingredients in skincare formulations.

[0101] Food industry: It can enhance the texture, stability, and bioavailability of nutrients and flavorings in food, and is also suitable for low-energy, surfactant-free production methods.

[0102] Pharmaceuticals: It provides drug delivery systems with controlled-release properties. Furthermore, precise control of the emulsion droplet size ensures consistent delivery of active pharmaceutical ingredients, improving therapeutic efficacy and reducing side effects.

[0103] Oil Extraction: The reversibility of the nanoemulsion of the present invention is beneficial to the oil extraction process. Both its stability and the flexibility of droplet size improve oil extraction efficiency.

[0104] Drug Delivery System: Due to the small size and high stability of the nanoemulsion of the present invention, it can be used to deliver drugs more effectively, enhance absorption, and provide a controlled release mechanism.

[0105] Template Material Synthesis: The uniformity of droplet size of the nanoemulsion of the present invention is beneficial for synthesizing nanomaterial templates with precise structures.

[0106] Thermal Regulation: Its unique reversible properties can be used for thermal regulation applications, such as smart windows that adjust transparency according to temperature to improve the energy efficiency of buildings.

[0107] Environmental Applications: It can help solve the problem of the solubility of harmful substances in the environment, such as oil spills. The technology provided by the present invention can control the dissolution and condensation of nanoemulsions to reduce the amount of oil-soluble toxic substances dissolved in the aquatic environment.

[0108] As used herein, the terms “approximately,” “substantially,” “truly,” and “about” are used to describe and explain a minor variation, and when used in conjunction with an event or situation, the term can refer to the exact occurrence of the event or situation, or approximately the occurrence of the event or situation. The term “about,” as used herein, regarding a given value or range, typically refers to a range of ±10%, ±5%, ±1%, or ±0.5% of the given value or interval, which can be understood herein as from one endpoint to another or between two endpoints. Unless otherwise stated, all ranges disclosed in this disclosure include endpoints. Furthermore, unless explicitly stated otherwise, the term “a” as used herein should be understood to include one or more; additionally, terms such as “first,” “second,” and “third” are used only as illustrative purposes and are not intended to give numerical meaning or to order them according to their importance.

[0109] The foregoing description is provided to illustrate and describe the invention and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations will be apparent to those skilled in the art.

[0110] The above embodiments were chosen and described in order to best explain the principles of the invention and its practical application, so that others skilled in the art can understand the various embodiments of the invention and the various modifications suitable for the intended particular use. Instruction Manual 11 / 11 Page 13 CN 121401164 A Figure 1A Figure 1B Instruction Manual Drawings 1 / 18 Page 14 CN 121401164 A Figure 1C Figure 1D Instruction Manual Drawings 2 / 18 Page 15 CN 121401164 A Figure 2 Figure 3A Instruction Manual Drawings 3 / 18 Page 16 CN 121401164 A Figure 3B Figure 3C Instruction Manual Drawings 4 / 18 Page 17 CN 121401164 A Figure 3D Figure 3E Instruction Manual Drawings 5 / 18 Page 18 CN 121401164 A Figure 3F Figure 3G Instruction Manual Drawings 6 / 18 Page 19 CN 121401164 A Figure 3H Figure 4A Instruction Manual Drawings 7 / 18 Page 20 CN 121401164 A Figure 4B Figure 5A Instruction Manual Drawings 8 / 18 Page 21 CN 121401164 A Figure 5B Figure 6A Appendix to the Instruction Manual, Page 9 / 18, 22 CN 121401164 A Figure 6B Figure 6C Appendix to the Instruction Manual, Page 10 / 18, 23 CN 121401164 A Figure 6D Figure 7A Appendix to the Instruction Manual, Page 11 / 18, 24 CN 121401164 A Figure 7B Figure 7C Appendix to the Instruction Manual, Page 12 / 18, 25 CN121401164 A Figure 8A Figure 8B Appendix 13 / 18 Page 26 CN 121401164 A Figure 8C Figure 9 Appendix 14 / 18 Page 27 CN 121401164 A Figure 10A Figure 10B Appendix 15 / 18 Page 28 CN 121401164 A Figure 10C Figure 10D Appendix 16 / 18 Page 29 CN 121401164 A Figure 10E Figure 11A Appendix 17 / 18 Page 30 CN 121401164 A Figure 11B Appendix 18 / 18 Page 31 CN 121401164 A Abstract Abdominal ultrasound examination method, system and device The present invention provides a method for generating nanoemulsions through cyclic thermal processes. The method is based on a biphasic liquid system including an immiscible first liquid phase and a second liquid phase. The system is heated to a temperature sufficient to vaporize the first liquid phase, whereby the vapor thereof dissolves into the second liquid phase to form a homogeneous mixture. Subsequently, the system is cooled to a temperature below the saturation point of the first liquid phase in the second liquid phase, thereby inducing nucleation of the first liquid phase within the second liquid phase to form nanodroplets.and generate the thermally induced nanoemulsion. Upon reheating, the nanoemulsion can dissociate and revert to the original biphasic liquid system. Through repeated heating-cooling cycles, a reversible and controllable method for preparing nanoemulsions is achieved, which is suitable for various applications including thermoresponsive smart delivery systems.

Claims

1. A method for preparing reversible thermally induced nanoemulsions without the addition of surfactants, characterized in that, include: A two-phase liquid system comprising a first liquid phase and a second liquid phase is provided, wherein the first and second liquid phases are immiscible; The two-phase liquid system is heated to a temperature that causes the first liquid phase to vaporize, thereby dissolving the first liquid phase vapor into the second liquid phase to form a homogeneous mixture. as well as The two-phase liquid system is cooled to a temperature below the saturation point of the first liquid phase vapor in the second liquid phase, thereby inducing the first liquid phase vapor to nucleate into nanodroplets in the second liquid phase, forming a reversible thermally induced nanoemulsion. The reversible thermally induced nanoemulsion decomposes into the biphase liquid system upon reheating, and the reversible thermally induced nanoemulsion is formed again by repeating the above steps.

2. The method according to claim 1, wherein the volume ratio of the first liquid phase to the second liquid phase is 0.01:1-100:

1.

3. The method according to claim 1, wherein the first liquid phase comprises water, and the second liquid phase comprises an oil selected from soybean oil, silicone oil, paraffin oil, hexadecane, toluene, and dichloromethane.

4. The method according to claim 1, wherein the reversible thermally induced nanoemulsion comprises water-in-oil (W / O) and oil-in-water (O / W) nanoemulsions.

5. The method according to claim 1, wherein the reversible thermally induced nanoemulsion has nanodroplets with an average diameter of 25-1000 nanometers.

6. The method according to claim 1, further comprising: The size of the nanodroplets can be controlled by adjusting the heating temperature and cooling rate.

7. The method according to claim 1, wherein, During the cooling step, the temperature of the first liquid phase is lower than the temperature of the second liquid phase.

8. The method according to claim 1, wherein the heating temperature of the two-phase liquid system is lower than the boiling point of the first liquid phase and the second liquid phase, and the cooling temperature is between 10°C and 40°C.

9. The method according to claim 1, wherein the vapor formed in the first liquid phase during heating reaches a supersaturated state in the second liquid phase, and condenses and nucleates near the interface between the first liquid phase and the second liquid phase during the cooling process.

Images