Application of particle stabilizer, oil-in-oil Pickering emulsion as well as preparation method and application of oil-in-oil Pickering emulsion

Abstract

The invention discloses application of a particle stabilizer, an oil-in-oil Pickering emulsion as well as a preparation method and application of the oil-in-oil Pickering emulsion, and relates to the technical field of emulsion preparation. The particle stabilizer is used for preparing the oil-in-oil Pickering emulsion, and the particle stabilizer is solid insoluble nanoparticles and is selected from one or more of inorganic nanoparticles, organic nanoparticles, composite oleophobic nanoparticles and stimuli-responsive nanoparticles. The preparation method of the oil-in-oil Pickering emulsion comprises the following steps: mixing the first oil phase, the second oil phase and the particle stabilizer, and carrying out an emulsification technology to obtain the oil-in-oil Pickering emulsion. According to the emulsion system prepared by the invention, the oil phase components with different polarity differences are reasonably matched, and the oil phase type is flexibly selected according to specific requirements of target application, so that the environmental adaptability and the function application range of the emulsion can be remarkably improved, and the emulsion system has a good application prospect.

Description

Technical Field

[0001] This application relates to the field of emulsion preparation technology, specifically to the application of a particle stabilizer, an oil-in-oil Pickering emulsion, its preparation method, and its application. Background Technology

[0002] Currently, emulsion technology is widely used in many fields. Traditional emulsion systems typically include oil-in-water (W / O) and water-in-oil (O / W) emulsions, which are formed through the interfacial interaction between the aqueous and oil phases. Oil-in-oil Pickering emulsions, on the other hand, are systems that use solid particles as emulsifiers and utilize the interfacial interaction between the oil phases to stabilize the emulsion. Compared to traditional W / O or O / W emulsions, oil-in-oil emulsions not only avoid the use of an aqueous phase but also significantly improve their adaptability to environmental changes, exhibiting unique advantages, especially in applications where water-sensitive reactions must be avoided. As described in patent number CN202080105965.0, the preparation of polyurea / polyurethane microcapsules using oil-in-water emulsions is not conducive to long-term storage of raw materials before the reaction due to the presence of the aqueous phase. Compared to traditional aqueous dispersion systems, non-aqueous emulsion systems have attracted widespread attention because they can avoid side reactions caused by aqueous phases to water-sensitive substances.

[0003] Oil-in-oil picking emulsions, with their low interfacial tension, are widely used in high-end cosmetics, pharmaceutical delivery, food processing, coatings, nanotechnology, environmental remediation, and many other fields. However, the preparation of oil-in-oil picking emulsions still faces challenges in current technologies. For example, due to the low interfacial tension between the oil phases, stratification or instability can easily occur during emulsification.

[0004] Therefore, there is an urgent need to develop a new method for preparing oil-in-oil Pickering emulsions, optimizing aspects such as interface stability, oil phase selection, solid particle functionalization, and emulsion application areas, to promote its application in a wider range of fields, especially in innovative applications in high-performance coatings, drug delivery, and food packaging materials.

[0005] Application content

[0006] To address the deficiencies or improvement needs of existing technologies, this application provides an application of a particle stabilizer, an oil-in-oil Pickering emulsion, a preparation method thereof, and its applications. Specifically, the oil phase in the oil-in-oil Pickering emulsion of this application is a non-aqueous organic phase with appropriate polarity characteristics. The oil-in-oil Pickering emulsion prepared using this method, through reasonable design and control of the compatibility differences between the oil phases and the selection of the solid particle stabilizer, can be widely used in various fields.

[0007] To achieve the above technical objectives, this application mainly adopts the following technical solution:

[0008] In a first aspect, this application discloses the application of a particulate stabilizer in the preparation of an oil-in-oil Pickering emulsion, wherein the particulate stabilizer is a solid insoluble nanoparticle selected from one or more of inorganic nanoparticles, organic nanoparticles, composite oleophobic nanoparticles, and stimuli-responsive nanoparticles.

[0009] Secondly, this application discloses an oil-in-oil Pickering emulsion, comprising a first oil phase, a second oil phase, and a particle stabilizer. The first and second oil phases are immiscible organic solvents, neither of which contains free water or hydroxyl functional groups, and the solubility parameters of the first and second oil phases must meet the following requirements. .

[0010] Thirdly, this application discloses a method for preparing an oil-in-oil Pickering emulsion as described in the second aspect, wherein the first oil phase, the second oil phase, and a particle stabilizer are mixed and then subjected to emulsification technology. The emulsification technology is selected from either mechanical stirring emulsification or magnetic stirring emulsification, and the stirring time is [not specified]. The stirring speed is .

[0011] Fourthly, this application discloses the use of an oil-in-oil Pickering emulsion as described in the second aspect or an oil-in-oil Pickering emulsion prepared by the method of the third aspect in the preparation of a media system (including but not limited to isocyanates / amines, peroxides / reducing agents) for isolating and delaying uncontrollable reactions that occur upon direct contact and / or for inhibiting the degradation of easily hydrolyzed active ingredients (including but not limited to easily hydrolyzed or oxidized small molecule organic compounds, polymers / precursors, nutrients / natural products) and / or for inhibiting the reaction of easily oxidized active ingredients.

[0012] Furthermore, the present application discloses the application of an oil-in-oil Pickering emulsion as described in the second aspect or an oil-in-oil Pickering emulsion prepared by the method of the third aspect in the delivery of easily oxidized or easily hydrolyzed products as a drug delivery system.

[0013] Compared with the prior art, this application has at least the following beneficial effects:

[0014] (1) This application utilizes solid particulate stabilizers to prepare oil-in-oil Pickering emulsions, which can stabilize the oil phase interface and effectively prevent the aggregation, stratification, or coalescence of oil phase droplets, thereby ensuring the stability of the emulsion. Compared with traditional water-in-oil (W / O) emulsions, oil-in-oil emulsions have a more compact structure and lower interfacial tension, enabling them to remain stable during long-term storage without the need for excessive chemical stabilizers, thus reducing the impact of external factors on emulsion quality. In the fields of coatings, food packaging, and cosmetics, this high stability ensures the long-term performance of products under extreme environments (such as high temperature, high humidity, and ultraviolet radiation).

[0015] (2) The method for preparing oil-in-oil Pickering emulsions provided in this application uses solid particle stabilizers instead of traditional surfactants, thus achieving a green and environmentally friendly emulsion system. Surfactants used in traditional emulsions may cause environmental pollution, especially for aqueous emulsions, where water-soluble surfactants are often discharged into wastewater, leading to water pollution. Oil-in-oil Pickering emulsions use a non-aqueous phase as the medium, avoiding the generation of water-soluble pollutants, and the solid particle stabilizers themselves have low biotoxicity, meeting the requirements of green chemistry and sustainable development.

[0016] (3) The oil-in-oil Pickering emulsion provided in this application has good controllability. The particle size, dispersibility and stability of the emulsion can be precisely adjusted according to different application requirements by adjusting the polar composition of the oil phase, the type of particle stabilizer and the control conditions in the emulsification process. This flexibility makes oil-in-oil emulsions widely used in many industries.

[0017] (4) The oil-in-oil Pickering emulsion provided in this application uses a non-aqueous organic phase system as the reaction medium, which avoids the hydrolysis and oxidation reactions caused by water relative to some water-sensitive active substances, such as drug molecules, vitamins, and fat-soluble active ingredients, in traditional emulsion systems. Attached Figure Description

[0018] Figure 1 The graph shows the polyurea reaction process and degree of polymerization changes in different polyurea oil-in-oil Pickering emulsions; the blue curve in the figure represents the trend of emulsification degree changing with stirring time; the red dashed line and the gray dashed line represent the degree of polyurea polymerization under emulsion protection (controllability of the emulsion to the polyurea reaction) and without emulsion protection, respectively.

[0019] Figure 2Microscopic images of oil-in-oil Pickering emulsions prepared in Experimental Example 1 using different mass ratios of dimethicone and soybean oil as the oil phase (a ~ h, the ratios of dimethicone and soybean oil are 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9, respectively).

[0020] Figure 3 The images show macroscopic diagrams of oil-in-oil Pickering emulsions prepared in Experiment 1 using different mass ratios of dimethicone and soybean oil as the oil phase, after standing and phase separation (the ratios of dimethicone and soybean oil in a to h are 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, and 1:9, respectively).

[0021] Figure 4 Microscopic images (A) and macroscopic images (B) of the emulsion formed by dimethicone and amine chain extender in Experimental Example 2 (a~d: the ratios of dimethicone to amine chain extender are 8:2, 7:3, 6:4, and 5:5, respectively).

[0022] Figure 5 The effect of oil-in-oil Pickering emulsions with different concentrations of particulate stabilizer added on the polyurea reaction in Experiment Example 3 (a ~ d: added with different concentrations of particulate stabilizer). , , , Particle stabilizers);

[0023] Figure 6 The diagram shows the effect of the two mixed oil phases before stirring (a), forming an emulsion (b), and reactive polymerization (c) in Example 2.

[0024] Figure 7 The left and right images in the middle are the magnetic responsiveness samples prepared in Example 11. Macroscopic and microscopic images of oil-in-oil Pickering emulsions stabilized by nanoparticles;

[0025] Figure 8 The images show a 20x (A) and a 100x (B) magnified micrograph of the oil-in-oil Pickering emulsion prepared in Example 9.

[0026] Figure 9 Micrograph of the oil-in-oil Pickering emulsion prepared in Example 7;

[0027] Figure 10 This is a diagram illustrating the effect of simulated in vitro drug release in Example 13, comparing the effects of having and not having emulsion protection. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application. Reagents not specifically described in detail herein are all conventional reagents and are commercially available; methods not specifically described in detail are all conventional experimental methods and can be learned from the prior art.

[0029] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence, nor do they substantially limit the technical features thereafter. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0030] For the purpose of better understanding this application and not limiting its scope, all figures indicating quantities, percentages, and other numerical values ​​used herein should, in all cases, be understood to be modified by the word "approximately." Therefore, unless otherwise stated, the numerical parameters listed in the specification and appended claims are approximate values ​​and may vary depending on the desired properties being sought. Each numerical parameter should at least be considered as obtained based on reported significant figures and through conventional rounding methods.

[0031] This application discloses the application of particulate stabilizers in the preparation of oil-in-oil Pickering emulsions. The particulate stabilizers are solid insoluble nanoparticles selected from one or more of inorganic nanoparticles, organic nanoparticles, composite oleophobic nanoparticles, and stimuli-responsive nanoparticles.

[0032] In some embodiments, the inorganic nanoparticles are selected from... Nanoparticles Nanoparticles Nanoparticles, bentonite nanoparticles, kaolin nanoparticles, or any combination thereof; the organic nanoparticles are selected from polystyrene and polymethyl methacrylate (PMMA); the composite oleophobic nanoparticles are selected from silica-polystyrene composite nanoparticles, alumina-polyurethane composite nanoparticles, and magnetically responsive nanoparticles with an oleophobic coating on the surface. Any type of nanoparticle; the stimulus-responsive nanoparticle is selected from thermosensitive nanoparticles modified with propyltrimethoxysilane. Nanoparticles, surface-grafted photosensitive azophenyl groups Nanoparticles Any type of nanoparticle.

[0033] Stimulus-responsive nanoparticles can undergo reversible wettability changes under specific external stimuli (such as temperature, light, or magnetic fields), thereby modulating the stability of emulsions. This wettability change can lead to a stabilization-demulsification switching of the emulsion system, effectively controlling the structure of the emulsion and thus regulating the subsequent polymerization time or chain extension reaction.

[0034] Using magnetic responsiveness Nanoparticles, acting as particulate stabilizers, can modulate the stability of emulsions under varying magnetic fields. For example, when an external magnetic field is applied, Magnetic nanoparticles are positioned and aligned along magnetic field lines under the influence of a magnetic field, which causes changes in the distribution of the oil phase in the emulsion, thereby achieving demulsification or repolymerization of the emulsion.

[0035] In some embodiments, the particle size of the particulate stabilizer is The preferred option is... .

[0036] In some embodiments, the wettability of the particle surface can also be adjusted by surface modification (such as grafting alkyl chains, fluorinated chains, or silanization treatment) to enable the particles to form a stable contact angle between the two oil phases, ensuring that the particles are firmly fixed at the interface and preventing the particles from falling off the interface.

[0037] This application also discloses an oil-in-oil Pickering emulsion, comprising a first oil phase, a second oil phase, and a particle stabilizer. The first and second oil phases are immiscible organic solvents, neither of which contains free water or hydroxyl functional groups, and the solubility parameters of the first and second oil phases must meet certain requirements. Under normal circumstances, the solubility parameters of the first and second oil phases meet the above requirements. However, in some special cases, the solubility parameters of the two oil phases are different. These molecules also exhibit incompatibility due to the different intermolecular forces. Examples include liquid paraffin and benzyl silicone oil, and vegetable oil and dimethicone.

[0038] In this application, to better understand the formation of oil-in-oil emulsions, a quantitative description of the traditional "like dissolves like" principle is provided. , and Three intermolecular forces are used to comprehensively describe the solubility of a substance, among which : Represents dispersion force (van der Waals force); : Indicates polar forces (dipole-dipole interactions); : Indicates hydrogen bonding force (the ability to form hydrogen bonds).

[0039] According to Hansen's dissolution parameter theory (HSP), the dissolution parameters of the two oil phases in the O / O emulsion must meet the following requirements. ;in

[0040]

[0041] in : Represents dispersion force (van der Waals force); : Indicates polar forces (dipole-dipole interactions); : Represents hydrogen bonding force (the ability to form hydrogen bonds); where A and B represent two different oil phases. The distance between the two solutions in this three-dimensional space is calculated. To measure their similarity. The smaller the value, the closer the molecular forces between the two, and the better the compatibility. A larger value indicates a greater difference in the forces acting on the particles, making them difficult to mix. R0 can be obtained through experimental fitting.

[0042] In some embodiments, in the first oil phase and the second oil phase, the phase with a larger mass is the continuous oil phase, and the phase with a smaller mass is the dispersed oil phase, and the mass ratio of the dispersed oil phase to the continuous oil phase is 1:9 to 1:2. Optionally, the mass ratio of the dispersed oil phase to the continuous oil phase is 2:8 to 4:6.

[0043] The particulate stabilizer is dispersed in a continuous phase, and the mass fraction of the particulate stabilizer is equal to the mass of the continuous phase. Preferably, the mass fraction of the particulate stabilizer is equal to the mass of the continuous phase. ;

[0044] The first oil phase is selected from one or more of octanol, nonanol, n-hexane, liquid paraffin, fish oil, or vegetable oil; the second oil phase is selected from one or more of xylene, dibenzyl ether, benzyl benzoate, silicone oil, dimethyl silicone oil, or benzyl silicone oil. Effective droplet phase separation and interface control are achieved through the polarity differences between the above-mentioned continuous oil phase and dispersed oil phase.

[0045] This application also discloses a method for preparing the oil-in-oil Pickering emulsion as described above, wherein the first oil phase, the second oil phase, and a particle stabilizer are mixed and then emulsified. The emulsification technique is selected from either mechanical stirring emulsification or magnetic stirring emulsification, and the stirring time is [not specified]. The stirring speed is .

[0046] Taking the synthesis of polyurea oil-in-oil Pickering emulsions as an example, the stirring speed is crucial to emulsion formation and polyurea polymerization. Preferably, the stirring time is 5 to 60 seconds, and the stirring speed is 50 to 200 r / min.

[0047] Furthermore, to form an O / O type Pickering emulsion and achieve the controllable synthesis of polyurea, the stirring time t (s) and stirring speed n (r / min) satisfy the empirical coupling relationship described by the following equation:

[0048]

[0049] Where A is a system constant related to the viscosity and particle concentration of the oil phase / emulsion, and a is the stirring dependence index (preferably 1.5~2.2). Minimum necessary stirring time (system inertia / wetting response time). A. It can be obtained by performing least squares fitting on several (n, t) working conditions in a given raw material system.

[0050] Furthermore, the degree of emulsion formation is expressed as a dimensionless process parameter. The expression, defined as "interfacial particle adsorption sufficiency / formation degree," can be approximated by the following formula under conditions of 25±1 ℃ and relative humidity ≤50%:

[0051]

[0052] when When the emulsion reaches a state where it can be used for subsequent controlled polyurea synthesis, it is considered to have reached a state where it can be used for subsequent controlled polyurea synthesis.

[0053] Correspondingly, the polyurea reaction process exhibits a certain degree of delay under the emulsion coating effect, as indicated by the degree of reaction progress. The normalized conversion of the polyurea reaction (the larger the value, the more advanced the reaction) can be represented by the following exponential decay model:

[0054]

[0055] in, The apparent rate constant under protected conditions (preferably 0.03 s⁻¹) -1 ), t is the apparent delay time (preferably ≥2-6 s), and t is the stirring time; for.

[0056]

[0057] in, This represents the residual activity fraction of the polyurea reaction in the system under conditions where no emulsion interface protection is formed. The higher the value, the less significant the reaction has been. The smaller the value, the more likely the polyurea chain extension reaction has occurred on a large scale, and the more likely the system is to exhibit heterogeneous phenomena such as local solidification and phase separation; t is the stirring time.

[0058] Furthermore, the area between the emulsion formation curve and the polyurea reaction curve can be used to quantify the coating and protective effect of the O / O type Pickering emulsion on the polyurea synthesis process and the width of the controllable window. Specifically: when the emulsion formation process follows... The reaction process of polyurea after being coated with emulsion follows At that time, the time corresponding to the intersection of the two curves This represents the critical moment when the degree of emulsion formation and the progress of the polyurea reaction reach equilibrium. Before this point (t ∈ [0, ..., ...), ... The emulsion preferentially forms and has a significant coating inhibition effect on the polyurea reaction; its corresponding area can be expressed by the following formula:

[0059]

[0060] in, This indicates the size of the "controllable operating window." The larger the value, the longer the period in which the emulsion has formed and the polyurea has not yet polymerized on a large scale. This is beneficial for the full dispersion of reactants and avoids local solidification.

[0061] Furthermore, the area between the polyurea curves in the unprotected and protected states can be used to quantify the reaction delay effect of emulsion coating, which can be expressed as:

[0062]

[0063] in, For the maximum stirring time (e.g., 60 s), This indicates that only values ​​greater than zero are considered. The delay area. The larger the value, the more significant the interfacial coating effect of the Pickering emulsion, which can effectively slow down the polymerization rate of polyurea, increase the controllable polymerization time window, and reduce the risk of agglomeration or solidification caused by excessively rapid reaction.

[0064] This application can establish a coupling relationship between stirring time and stirring speed by pre-experimenting key process parameters such as emulsion formation degree (Y), coupling parameter (A), and stirring time (t) based on the target droplet particle size and dispersed phase mass ratio, and further quantify to obtain the optimal stirring process window. Preferably, the stirring process is a stirring rate of 60~80 r / min and a stirring time of 7.5~13 s. Under these conditions, the emulsion interface is fully formed and the polyurea reaction is in a controllable delayed state, significantly improving the microscopic uniformity of the final O / O Pickering emulsion and the process stability of the polyurea reaction.

[0065] In some embodiments, when the Pickering emulsion is a polyurea-type oil-in-oil Pickering emulsion, the following emulsification step is included:

[0066] The oil phase dispersion was mixed with the isocyanate compound to obtain the first mixed oil phase;

[0067] The oil phase continuous phase is mixed with an amine chain extender to obtain a second mixed oil phase;

[0068] The mixture of the first mixed oil phase, the second mixed oil phase, and the particulate stabilizer is obtained by emulsification.

[0069] The mixing ratio of the oil phase dispersion to the isocyanate is 9:1 to 7:3 by weight, and optionally 9:1 to 6:4.

[0070] The mixing ratio of the oil phase continuous phase and the amine chain extender is 5:5 to 8:2 by weight, and optionally 6:4 to 8:2.

[0071] The dispersed phase has relatively high polarity, which is beneficial for dissolving isocyanate components and provides a certain diffusion driving force in subsequent reactions; the continuous phase has lower polarity, which is suitable for dispersing amine chain extenders, forming a relatively stable continuous phase droplet structure. The two oils are immiscible, ensuring the formation of a clear interface boundary, which is conducive to the construction of Pickering emulsion structures.

[0072] In some embodiments, when the Pickering emulsion is a polyurea-type oil-in-oil Pickering emulsion, the amine chain extender has low solubility in the selected organic phase (non-polar solvent) or is not completely miscible, requiring a further pre-emulsification step. Specifically, this includes the following pre-emulsification and emulsification steps:

[0073] Pre-emulsification: An amine chain extender is added to the second oil phase and mixed and stirred to form a primary emulsion, which serves as the dispersed phase;

[0074] An isocyanate compound is added to the first oil phase and mixed and stirred to obtain a first mixed oil phase, which serves as the continuous phase. A particle stabilizer is then added to the continuous phase.

[0075] Emulsification: The pre-emulsified primary emulsion is mixed with the first mixed oil phase containing a particulate stabilizer, and then emulsified using emulsification technology to form an oil-in-oil-in-oil Pickering emulsion.

[0076] In this step, a pre-emulsified oil-in-oil emulsion is used as the dispersed phase, and a first oil phase is used as the continuous phase. The particulate stabilizer is dispersed within the continuous phase, and a stable droplet structure is formed through interfacial adsorption of the particulate stabilizer. The first mixed oil phase not only serves as the continuous medium of the reaction system but also plays a role in interfacial regulation and film-forming support during the formation of the emulsion structure. It can encapsulate the dispersed phase droplets, inhibit component migration, and improve system stability.

[0077] In some embodiments, when the selected amine chain extender has low solubility in some solvents or is partially immiscible, the dispersibility and solubility of the amine chain extender in the organic phase can be improved by adding an appropriate amount of co-solvent, wherein the co-solvent is selected from one or more of ethanol, isopropanol, or propylene glycol, and includes the following steps:

[0078] The isocyanate compound is dissolved in the first oil phase to obtain the first mixed oil phase;

[0079] Add the amine chain extender to the co-solvent beforehand and stir until completely dissolved;

[0080] A co-solvent containing a dissolved amine chain extender is added to the second oil phase to obtain a second mixed oil phase;

[0081] The first mixed oil phase, the second mixed oil phase, and the particulate stabilizer are thoroughly mixed evenly.

[0082] The ratio of the co-solvent, amine chain extender, and second oil phase is 1:1:5 by mass.

[0083] In this step, the solubility of the amine chain extender in the non-aqueous organic phase is improved by adding an appropriate amount of co-solvent. The introduction of the co-solvent can effectively reduce the phase separation or local enrichment caused by the large difference between the polarity of the amine chain extender and the polarity of the oil phase, and ensure the uniformity and controllability of the subsequent polyurea controllable synthesis process.

[0084] In some embodiments, stimuli-responsive nanoparticles (such as magnetically responsive Fe3O4 nanoparticles) are used as interface stabilizers in the Pickering emulsion. By applying an external magnetic field (such as applying a permanent magnet or electromagnetic coil outside the emulsion system), the Fe3O4 nanoparticles can be caused to migrate or desorb at the emulsion interface due to magnetic force, thereby disrupting the adsorption equilibrium of the particles at the oil / oil interface. This allows for controllable delay of the polyurea reaction during the emulsion protection stage and rapid polymerization triggering in the later stages, promoting thorough mixing of isocyanate and amine chain extender within the system and facilitating a rapid polyurea reaction, significantly improving the reaction conversion rate and curing uniformity of the system.

[0085] In some embodiments, oleophobic nanoparticles with stimuli-responsive properties (such as photosensitive azophenyl group SiO2 nanoparticles) are used as interface stabilizers for Pickering emulsions. The resulting photosensitive particles undergo cis-trans isomerization under ultraviolet light (365 nm) irradiation, changing their surface wettability from oleophobic to relatively oleophilic; after exposure to visible light or in the dark (>420 nm), they reversibly revert to their oleophobic state. Utilizing this reversible photoresponsiveness, the adsorption and desorption behavior of the particles at the oil / oil interface can be controlled by adjusting the light conditions, thereby achieving reversible stabilization and demulsification regulation of oil-in-oil Pickering emulsions.

[0086] This application also discloses the application of the oil-in-oil Pickering emulsion as described above, or the oil-in-oil Pickering emulsion prepared by the above method, in the preparation of media systems (including but not limited to isocyanates / amines, peroxides / reducing agents) for isolating and delaying uncontrollable reactions that occur upon direct contact, and / or media systems for inhibiting the degradation of easily hydrolyzed active ingredients (including but not limited to easily hydrolyzed or oxidized small molecule organic compounds, polymers / precursors, nutrients / natural products) and / or media systems for inhibiting the reaction of easily oxidized active ingredients.

[0087] Taking drug delivery as an example, easily oxidized or hydrolyzed active substances are encapsulated in the dispersed phase, and their protection and controlled release are achieved through the oil-in-oil Pickering emulsion preparation method.

[0088] In some embodiments, easily oxidizable substances (such as vitamin C) and fat-soluble drugs (vitamin D3, vitamin E) are dissolved in an oil dispersion phase, effectively encapsulated using an oil-in-oil emulsion structure, and then uniformly distributed in the emulsion system through external emulsification. This encapsulation method effectively isolates moisture and oxygen, preventing oxidative degradation or hydrolytic deactivation of the active substances during storage and use.

[0089] The technical solution of this application will be further described below with reference to specific embodiments.

[0090] The raw materials used in the following examples are from the following sources:

[0091] Diphenylmethane diisocyanate (MDI-50): Purchased from Wanhua Chemical Group Co., Ltd.;

[0092] Isophorone diisocyanate (IPDI): Purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0093] Dimethicone and benzyl silicone oil: purchased from Shanghai Maclean Biochemical Technology Co., Ltd.

[0094] Diethyltoluenediamine and polyetheramine (D2000): purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0095] Soybean oil: Produced by Shandong Luhua Group Co., Ltd.;

[0096] SiO2 nanoparticles (CAS No.: 112945-52-5): purchased from Beijing Anbiqi Biotechnology Co., Ltd.; the model number for 200nm SiO2 nanoparticles is DNG-B006; the model number for 70nm SiO2 nanoparticles is DNG-B004.

[0097] Magnetic-responsive Fe3O4 nanoparticles (CAS No.: 1317-61-9): purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd. (nanoparticles of different sizes were separated by stepwise filtration using separation membranes with different pore sizes (50 ~ 1500 nm).

[0098] The preparation method of propyltrimethoxysilane modified thermosensitive SiO2 nanoparticles is as follows:

[0099] First, dissolve 1.0 g of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) in 10 mL of dilute hydrochloric acid (1×10⁻⁶). -3 In a solution containing 30% SiO2 sol, the mixture was sonicated for 30 min. Then, 20 g of 30% SiO2 sol was added to the reaction solution and reacted at 60°C for 2 hours. Next, an equal volume of anhydrous ethanol was added to the reaction solution, and the mixture was stirred at 120 r / min for 20 min to ensure thorough mixing. Following this, the mixture was dialyzed for 72 h using a dialysis bag (MW=8000), concentrated, and lyophilized. Finally, nanoparticles of different sizes were separated by stepwise filtration using membranes with different pore sizes (50 ~ 1500 nm).

[0100] The preparation method of SiO2 nanoparticles with surface grafted photosensitive azophenyl groups is as follows:

[0101] Dissolve 1.0 g of tetraethoxysilane (TEOS) in 10.0 mL of anhydrous ethanol, add 0.2 mL of concentrated hydrochloric acid as a catalyst, and stir for 30 min. Add 0.5 g of the photosensitizing monomer (azophenyl acrylate) and 0.015 g of the initiator (azobisisobutyronitrile) to the resulting sol, and stir at room temperature for 15 min to ensure complete dissolution and uniform distribution of the photosensitizing monomer. Irradiate with ultraviolet light for 1 h (wavelength 365 nm, light intensity 10 mW / cm²). 2 The process continues until photocrosslinked SiO2 particles are formed. After washing and freeze-drying, nanoparticles of different sizes are separated by stepwise filtration using separation membranes with different pore sizes (50 ~ 1500 nm).

[0102] The preparation method of magnetically responsive Fe3O4 nanoparticles with an oleophobic coating is as follows:

[0103] 0.5 g of an oleophobic silane coupling agent (trifluorochlorosilane) was dissolved in 10 mL of anhydrous ethanol to prepare a coupling agent solution. 0.3 g of magnetically responsive Fe3O4 nanoparticles were added to the coupling agent solution and sonicated for 30 minutes. Then, an appropriate amount of hydrochloric acid was added to adjust the pH to 4-5, and the reaction was allowed to proceed for 1 h. After the reaction was complete, the resulting product was washed with deionized water and lyophilized to obtain the desired product. Nanoparticles of different sizes were then separated by stepwise filtration using membranes with different pore sizes (50 ~ 1500 nm).

[0104] The preparation method of silica-polystyrene composite nanoparticles is as follows:

[0105] First, 1.0 g of SiO2 nanoparticles were added to 1.0 mL of (3-aminopropyl)triethoxysilane for amination. Then, 1.30 mL of 2-bromoisobutyryl bromide was added under alkaline conditions (pH≈11), and the reaction was carried out at room temperature for 12 h to obtain SiO2-Br. The SiO2-Br was washed and dried. 0.5 g of SiO2-Br, 15 mL of styrene containing 15 mg of inhibitor (p-tert-butylcatechol), 215 mg (1.5 mmol) of CuBr, and 470 mg (3 mmol) of 2,2′-bipyridine were stirred and polymerized at 90 °C for 10 h under nitrogen protection. After the reaction, the ungrafted polystyrene was washed with toluene and dried under vacuum at 40 °C to obtain silica-polystyrene composite nanoparticles. Nanoparticles of different sizes were separated by stepwise filtration using separation membranes with different pore sizes (50 ~ 1500 nm).

[0106] Example 1 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0107] (1) Weigh the first oil phase (liquid paraffin) and MDI-50 in a weight ratio of 90:10 and mix them thoroughly to obtain the first mixed oil phase; weigh the second oil phase (xylene) and amine chain extender (polyetheramine D2000) in a weight ratio of 80:20 and mix them to obtain the second mixed oil phase;

[0108] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. Silica-polystyrene composite nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the continuous phase mass.

[0109] (3) Mechanical stirring was used, with a stirring speed of 70 r / min and a stirring time of 12 s to form a stable oil-in-oil Pickering emulsion. After a 5-s delay, the emulsion began to react and precipitates appeared. After the polymerization reaction occurred, the reaction process was slowed down and ended after 4 s. Under the same formulation and environmental conditions, if MDI-50 and polyetheramine D2000 were in direct contact without using the above-mentioned Pickering emulsion, the two would react immediately and solidify rapidly; however, after using the oil-in-oil Pickering emulsion for spatial isolation and interface control, the apparent contact reaction between the two was delayed and slowed down.

[0110] Example 2 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0111] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 80:20 to obtain the first mixed oil phase; weigh the second oil phase (xylene) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0112] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. Silica-polystyrene composite nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the continuous phase mass.

[0113] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a 5-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 3 seconds before ending.

[0114] Example 3 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0115] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 60:40 to obtain the first mixed oil phase; weigh the second oil phase (xylene) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 55:45 to obtain the second mixed oil phase;

[0116] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0117] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a 5-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 2 seconds before ending.

[0118] Example 4 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0119] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 60:40 to obtain the first mixed oil phase; weigh the second oil phase (xylene) and mix it with the amine chain extender (diethyltoluene diamine) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0120] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0121] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a delay of 4 seconds, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 2 seconds before the reaction ended.

[0122] Example 5 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0123] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase; weigh the second oil phase (dibenzyl ether) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0124] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0125] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a 3-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 3 seconds before ending.

[0126] Example 6 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0127] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase; weigh the second oil phase (benzyl benzoate) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0128] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.8 wt% of the mass of the continuous phase.

[0129] (3) Mechanical stirring was used, with the stirring speed set at 50 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a 3-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 3 seconds before ending.

[0130] Example 7 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0131] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase; weigh the second oil phase (benzyl benzoate) and mix it with the amine chain extender (diethyltoluene diamine) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0132] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.8 wt% of the mass of the continuous phase.

[0133] (3) Mechanical stirring was used, with the stirring speed set to 100 r / min and the stirring time controlled to 12 seconds, to form a stable oil-in-oil Pickering emulsion. After a delay of 6 seconds, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 2 seconds before the reaction ended.

[0134] Example 8 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0135] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase; weigh the second oil phase (benzyl benzoate) and mix it with the amine chain extender (diethyltoluene diamine) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0136] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. SiO2 nanoparticles (particle size of 500 nm) were added to the continuous phase at an amount of 0.8 wt% of the mass of the continuous phase.

[0137] (3) Mechanical stirring was used, with the stirring speed set to 200 r / min and the stirring time controlled to 12 seconds, to form a stable oil-in-oil Pickering emulsion. After a 3-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 3 seconds until the reaction ended.

[0138] Example 9 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0139] (1) Pre-emulsification: Weigh the second oil phase (dimethicone oil, non-polar) and the amine chain extender (polyetheramine D2000) in a weight ratio of 70:30, mix them, stir and emulsify to obtain the primary emulsion as the dispersed phase;

[0140] (2) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 at a weight ratio of 70:30 to obtain the first mixed oil phase as the continuous phase; add SiO2 nanoparticles (particle size of 200 nm) to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0141] (3) Emulsification: The continuous phase with added nanoparticles and the dispersed phase are mixed at a mass ratio of 3:1.

[0142] (4) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil-in-oil Pickering emulsion. After a 5-second delay, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 5 seconds before ending.

[0143] Example 10 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0144] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase;

[0145] (2) Measure the cosolvent (ethanol), polyetheramine D2000 and dimethicone oil in a mass ratio of 1:1:5. Add the amine chain extender polyetheramine D2000 to the cosolvent ethanol in advance and stir until completely dissolved. Then add the cosolvent containing the amine chain extender to the second oil phase dimethicone oil to obtain the second mixed oil phase.

[0146] (3) The first mixed oil phase and the second mixed oil phase are mixed at a mass ratio of 1:3; the phase with the larger mass is used as the continuous phase, and the phase with the smaller mass is used as the dispersed phase. SiO2 nanoparticles (particle size of 200 nm) are added to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0147] (4) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. After a delay of 2 seconds, the emulsion began to precipitate and a polymerization reaction occurred, which lasted for 0.5 seconds before ending.

[0148] Example 11 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0149] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 60:40 to obtain the first mixed oil phase; weigh the second oil phase (xylene) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 55:45 to obtain the second mixed oil phase;

[0150] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. Magnetic responsive Fe3O4 nanoparticles (particle size of 200 nm) were added to the continuous phase at an amount of 0.5 wt% of the continuous phase mass.

[0151] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. The emulsion was placed in a magnetic field, and after a 1-second delay, the emulsion began to precipitate and undergo polymerization. The reaction ended after 2 seconds.

[0152] Example 12 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0153] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 60:40 to obtain the first mixed oil phase; weigh the second oil phase (xylene) and mix it with the amine chain extender (polyetheramine D2000) in a weight ratio of 55:45 to obtain the second mixed oil phase;

[0154] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase, and the phase with the smaller mass was used as the dispersed phase. Magnetic responsive Fe3O4 nanoparticles (particle size of 200 nm) with an oleophobic coating were added to the continuous phase at a mass of 0.5 wt% of the continuous phase.

[0155] (3) Mechanical stirring was used, with the stirring speed set at 70 r / min and the stirring time controlled at 12 seconds to form a stable oil-in-oil Pickering emulsion. The emulsion was placed in a magnetic field, and after a 1-second delay, the emulsion began to precipitate and undergo a polymerization reaction, which lasted for 3 seconds until the reaction ended.

[0156] Comparative Example 1 (Polyurea Synthesis)

[0157] The raw materials, proportions, and operating conditions were essentially the same as in Example 3: liquid paraffin + MDI-50, xylene + D2000, mass ratio 3:1, stirred at 70 r / min for 12 s, but without the addition of any particle stabilizer. Results: The emulsion rapidly separated into layers, the phase interface was unstable, the polyurea reaction showed localized rapid polymerization, and the product contained voids and flocculent agglomerates.

[0158] Comparative Example 2 (Polyurea Synthesis)

[0159] In Example 1, xylene was replaced with an aqueous phase to construct a conventional W / O emulsion, with the same dosages of MDI-50 and D2000 added as in Example 1. Operating conditions remained consistent. Results: Due to the presence of the aqueous phase, isocyanate underwent a side reaction, generating CO2, resulting in pores and a loose structure. The coating strength and density were significantly inferior to the oil-in-oil Pickering system.

[0160] As can be seen from Examples 1-12 and Comparative Examples 1-2, under the same raw materials and environmental conditions, when using an oil-in-oil Pickering emulsion containing a particulate stabilizer, the apparent contact reaction between isocyanate and amine chain extender changes from instantaneous (Δt≈0 s) to a significant and repeatable delay (Δt approximately 2-6 s), demonstrating stable spatial isolation and temporal control. In contrast, although the O / O emulsion without a particulate stabilizer (Comparative Example 1) is an O / O system, the interface lacks a particulate layer support, is prone to droplet demulsification, and is difficult to block direct migration between the two phases, thus no effective delay was observed (Δt≈0 s); while in the water-in-oil emulsion (Comparative Example 2), due to the introduction of an aqueous phase, isocyanate is prone to hydrolysis / side reactions at the interface, making it impossible to obtain a controllable delay window. In summary, O / O Pickering has three advantages over the two control groups: ① controllable timing (achieving a 2-6 s forming / transfer window); ② controllable side reactions (avoiding hydrolysis / side reactions caused by the aqueous phase); ③ process versatility (Δt and τ can be programmably adjusted by particle type / particle size / addition amount, solvent and stirring intensity).

[0161] Example 13 (Drug Delivery System)

[0162] (1) The first oil phase (soybean oil) and the fat-soluble drug (vitamin C) were weighed and mixed at a weight ratio of 75:25 to form the oil phase dispersion; the second oil phase dimethicone oil was weighed and used as the oil phase continuous phase.

[0163] (2) Mix the above-mentioned continuous oil phase and dispersed oil phase at a mass ratio of 3:1; add SiO2 nanoparticles (average particle size of 70 nm) to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0164] (3) Mechanical stirring was used, with the stirring speed set at 700 r / min and the stirring time controlled at 10 min to form a stable oil-in-oil Pickering emulsion.

[0165] The release of the drug was tested by simulating the in vivo environment. The specific method was as follows: The experiment simulated the in vivo environment using a permeate membrane diffusion cell to determine the in vitro release behavior of vitamin C from an oil-in-oil Pickering emulsion. First, 5 mL of the prepared oil-in-oil Pickering emulsion was placed in the upper chamber of the diffusion cell, and 50 mL of PBS (pH 7.4) was placed in the lower chamber. The experiment was conducted in a constant temperature water bath at 36 ± 0.5°C with a stirring rate of 50 rpm. Every 30 minutes, 5 mL of solution was sampled, and the vitamin C concentration in the solution was determined by high-performance liquid chromatography (HPLC) until the drug was substantially released. The release rate and behavior were analyzed by plotting a cumulative release curve to further evaluate the sustained-release effect and controllability of the emulsion.

[0166] Experimental results show that, compared with no emulsion protection, emulsion protection significantly reduces the hydrolysis and deterioration of vitamin C at 36°C, resulting in a higher cumulative release curve of the effective drug throughout the entire time course. This indicates that emulsion protection not only delays deterioration but also increases the absorption ratio, achieving a stable and controllable drug delivery effect.

[0167] Example 14 (Drug Delivery System)

[0168] (1) The first oil phase (fish oil) and the fat-soluble drug (vitamin E) were weighed and mixed at a weight ratio of 75:25 to form the oil phase dispersion; the second oil phase dimethicone oil was weighed and used as the oil phase continuous phase.

[0169] (2) The above-mentioned continuous oil phase and dispersed oil phase were mixed at a mass ratio of 3:1; magnetically responsive Fe3O4 nanoparticles (average particle size of 60 nm) with an oleophobic coating were added to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0170] (3) Mechanical stirring was used, with a stirring speed of 700 r / min and a stirring time of 20 min to form a stable oil-in-oil Pickering emulsion. The drug release was tested using the same test method as in Example 13, simulating an in vivo environment. The experimental results showed that under the stimulation of temperature change (36℃), the drug in the emulsion was slowly released in the in vitro environment, with a release time of 200 min. The release rate was controllable, and the cumulative release rate was greater than that without emulsion protection.

[0171] Example 15 (Drug Delivery System)

[0172] (1) The first oil phase (fish oil) and the fat-soluble drug (vitamin D3) were weighed and mixed at a weight ratio of 75:25 to form the oil phase dispersion; the second oil phase dimethicone oil was weighed and used as the oil phase continuous phase.

[0173] (2) Mix the above-mentioned continuous oil phase and dispersed oil phase at a mass ratio of 3:1; add propyltrimethoxysilane-modified thermosensitive SiO2 nanoparticles (average particle size of 60 nm) to the continuous phase at an amount of 0.5 wt% of the mass of the continuous phase.

[0174] (3) Mechanical stirring was used, with a stirring speed of 700 r / min and a stirring time of 10 min, to form a stable oil-in-oil Pickering emulsion. The drug release was tested using the same test method as in Example 13, simulating an in vivo environment. The experimental results showed that under the stimulation of temperature change (36℃), the drug in the emulsion was slowly released in the in vitro environment, with a release time of 200 min. The release rate was controllable, and the cumulative release rate was greater than that without emulsion protection.

[0175] Example 16 (Synthesis of polyurea-type oil-in-oil Pickering emulsion)

[0176] (1) Weigh the first oil phase (liquid paraffin) and mix it with MDI-50 in a weight ratio of 70:30 to obtain the first mixed oil phase; weigh the second oil phase (benzyl benzoate) and mix it with the amine chain extender (diethyltoluene diamine) in a weight ratio of 75:25 to obtain the second mixed oil phase;

[0177] (2) The first mixed oil phase and the second mixed oil phase were mixed at a mass ratio of 1:3; the phase with the larger mass was used as the continuous phase and the phase with the smaller mass was used as the dispersed phase. Surface-grafted photosensitive azophenyl group SiO2 nanoparticles (particle size 200 nm) were added to the continuous phase at an amount of 0.8 wt% of the continuous phase mass.

[0178] (3) Mechanical stirring was used with a stirring speed of 80 r / min for 10 seconds to form a stable oil-in-oil Pickering emulsion. After 5 min of UV irradiation, the emulsion interface gradually became unstable, the droplets merged, and the system showed stratification.

[0179] Experiment 1: Investigating the effect of different ratios of dimethicone and soybean oil on the properties of Pickering emulsions.

[0180] The specific steps are as follows:

[0181] (1) In the experiment, dimethicone oil and soybean oil were selected as the continuous phase and dispersed phase, respectively. By adjusting the ratio of the two, the effects of different oil phase combinations on the stability and microstructure of the emulsion were investigated. The mass ratios of the continuous phase and dispersed phase were set as follows: 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, and 1:9.

[0182] (2) The specific method for preparing the emulsion using an 8:2 ratio as an example is as follows: Dimethicone oil and soybean oil are weighed and mixed in a mass ratio of 8:2. The phase with the larger mass is used as the continuous phase, and the phase with the smaller mass is used as the dispersed phase. Silica-polystyrene composite nanoparticles (particle size of 200 nm) are added to the continuous phase, with the addition amount accounting for 0.5 wt% of the mass of the continuous phase. Magnetic stirring emulsification technology is used, with the stirring speed set to 70 r / min and the stirring time controlled to 12 seconds.

[0183] The preparation method of emulsion is the same under other mass ratio conditions, the only difference being the mass ratio of the continuous phase and the dispersed phase.

[0184] (3) After the emulsion was prepared, its microstructure was observed under a microscope, and the results are as follows: Figure 2 As shown, the particle size and dispersibility of the emulsion exhibit the following characteristics under different oil phase ratios: when the quality of dimethicone oil is relatively high, the emulsion particles are more uniform. When the proportion of soybean oil increases, the emulsion particle size is larger, and the dispersibility decreases. Further analysis of its stability yields the following results: Figure 3 As shown, within the same 72-hour settling period, adjusting the oil phase ratio significantly affects the emulsion's storage stability. Optimizing the oil phase ratio can significantly mitigate emulsion stratification.

[0185] Combination Figure 2 and Figure 3 It can be concluded that the preferred mass ratio of the continuous phase and the dispersed phase in this invention is 8:2-6:4.

[0186] Experiment 2 investigated the effects of pre-emulsions prepared by mixing different proportions of dimethicone oil and amine chain extender (polyetheramine D2000) (refer to the preparation of the primary emulsion in Example 9).

[0187] (1) The effects of different ratios of dimethicone and amine chain extender on the stability and microstructure of the emulsion were studied by adjusting the ratio of dimethicone to amine chain extender. The mass ratios of dimethicone to amine chain extender set in the experiment were 8:2, 7:3, 6:4, and 5:5.

[0188] (2) The experiment used the same preparation method as in Example 9. After mixing the two substances, they were emulsified by magnetic stirring.

[0189] (3) After the emulsion is prepared, its macroscopic and microscopic structures are observed, and the results are as follows: Figure 4As shown. By adjusting the ratio of dimethicone to amine chain extender, the microstructure and macroscopic stability of the emulsion change significantly. At higher dimethicone ratios (e.g., 8:2, 7:3), the emulsion exhibits better stability and a finer particle distribution; while at lower ratios (e.g., 5:5), the emulsion may exhibit larger particles and poorer stability. The optimized ratio helps improve the performance of the emulsion, thereby ensuring its stable dispersion as a dispersed phase in the continuous phase. Therefore, the preferred ratio of dimethicone to amine chain extender in this invention is 8:2-7:3.

[0190] Experimental Example 3: Investigating the effect of oil-in-oil Pickering emulsions with different concentrations of particulate stabilizers on the polyurea reaction.

[0191] The specific steps are as follows:

[0192] (1) The effect of oil-in-oil Pickering emulsion prepared by adding 0 wt%, 0.1 wt%, 0.2 wt%, and 0.4 wt% SiO2 nanoparticle stabilizers respectively in the experiment.

[0193] (2) All experiments used the basic preparation method of Example 4, with the only differences being the amount of SiO2 nanoparticles added and the stirring time (10s).

[0194] (3) After the emulsion was prepared, it was allowed to stand for 48 hours and then separated into layers. The macroscopic structure was observed, and the results were as follows: Figure 5 As shown, the formation of flocculent aggregates in group ad decreased progressively, while group d showed no obvious aggregates. The concentration of particulate stabilizer significantly improved the stability of oil-in-oil Pickering emulsions. An appropriate concentration of particulate stabilizer (e.g., 0.4 wt%) can effectively prevent emulsion stratification and reactions between emulsion-loaded substances.

[0195] The above description is merely a preferred embodiment of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application.

Claims

1. The application of particulate stabilizers in the preparation of oil-in-oil Pickering emulsions, wherein the particulate stabilizers are solid insoluble nanoparticles selected from one or more of inorganic nanoparticles, organic nanoparticles, composite oleophobic nanoparticles, and stimuli-responsive nanoparticles.

2. The application according to claim 1, wherein the inorganic nanoparticles are selected from... Nanoparticles Nanoparticles Nanoparticles, bentonite nanoparticles, kaolin nanoparticles, or any one or more thereof; the organic nanoparticles are selected from polystyrene and polymethyl methacrylate (PMMA); the composite oleophobic nanoparticles are selected from silica-polystyrene composite nanoparticles, alumina-polyurethane composite nanoparticles, and magnetically responsive nanoparticles with an oleophobic coating. Any type of nanoparticle; the stimulus-responsive nanoparticle is selected from thermosensitive nanoparticles modified with propyltrimethoxysilane. Nanoparticles, surface-grafted photosensitive azophenyl groups Nanoparticles, magnetic responsiveness Any type of nanoparticle.

3. In the application according to claim 1, the particle size of the particulate stabilizer is... The preferred option is... .

4. An oil-in-oil Pickering emulsion, comprising a first oil phase, a second oil phase, and a particle stabilizer, wherein the first and second oil phases are immiscible organic solvents, neither of which contains free water or hydroxyl functional groups, and the solubility parameters of the first and second oil phases conform to... .

5. The oil-in-oil Pickering emulsion according to claim 4, wherein in the first oil phase and the second oil phase, the phase with a larger mass is the continuous oil phase, and the phase with a smaller mass is the dispersed oil phase, and the mass ratio of the dispersed oil phase to the continuous oil phase is 1:9 to 1:2, optionally, the mass ratio of the dispersed oil phase to the continuous oil phase is 2:8 to 4:6; The particulate stabilizer is dispersed in a continuous phase, and the mass fraction of the particulate stabilizer is equal to the mass of the continuous phase. Preferably, the mass fraction of the particulate stabilizer is equal to the mass of the continuous phase. ; The first oil phase is selected from one or more of octanol, nonanol, n-hexane, liquid paraffin, fish oil, or vegetable oil; the second oil phase is selected from one or more of xylene, dibenzyl ether, benzyl benzoate, silicone oil, dimethicone, or benzyl silicone oil.

6. A method for preparing an oil-in-oil Pickering emulsion as described in any one of claims 4-5, comprising mixing a first oil phase, a second oil phase, and a particle stabilizer, followed by emulsification, wherein the emulsification technique is selected from either mechanical stirring emulsification or magnetic stirring emulsification, and the stirring time is [not specified]. The stirring speed is .

7. The preparation method according to claim 6, wherein when the Pickering emulsion is a polyurea-type oil-in-oil Pickering emulsion, the method comprises the following emulsification step: The oil phase dispersion was mixed with the isocyanate compound to obtain the first mixed oil phase; The oil phase continuous phase is mixed with an amine chain extender to obtain a second mixed oil phase; The mixture of the first mixed oil phase, the second mixed oil phase, and the particulate stabilizer is obtained by emulsification. The mixing ratio of the oil phase dispersion to the isocyanate is 9:1 to 6:4 by weight, and optionally 9:1 to 7:

3. The mixing ratio of the oil phase continuous phase and the amine chain extender is 5:5 to 8:2 by weight, and optionally 6:4 to 8:

2.

8. The preparation method according to claim 7, wherein the Pickering emulsion is a polyurea-type oil-in-oil Pickering emulsion, and the selected second oil phase is a non-polar solvent, i.e. Then, the process includes the following pre-emulsification and emulsification steps: Pre-emulsification: An amine chain extender is added to the second oil phase and mixed and stirred to form a primary emulsion, which serves as the dispersed phase; An isocyanate compound is added to the first oil phase and mixed with stirring to obtain a first mixed oil phase, which serves as the continuous phase. A particle stabilizer is then added to the continuous phase. Emulsification: The pre-emulsified primary emulsion is mixed with the first mixed oil phase containing a particulate stabilizer, and then emulsified using emulsification technology to form a polyurea-type oil-in-oil Pickering emulsion.

9. The preparation method according to claim 7, further comprising adding a co-solvent, wherein the co-solvent is selected from one or more of ethanol, isopropanol, or propylene glycol, comprising the following steps: The isocyanate compound is dissolved in the first oil phase to obtain the first mixed oil phase; Add the amine chain extender to the co-solvent beforehand and stir until completely dissolved; A co-solvent containing a dissolved amine chain extender is added to the second oil phase to obtain a second mixed oil phase; The first mixed oil phase, the second mixed oil phase, and the particulate stabilizer are thoroughly mixed evenly. The ratio of the co-solvent, amine chain extender, and second oil phase is 1:1:5 by mass.

10. The use of the oil-in-oil Pickering emulsion as described in any one of claims 4-5 or the oil-in-oil Pickering emulsion prepared by the method of any one of claims 6-9 in the preparation of media systems (including but not limited to isocyanates / amines, peroxides / reducing agents) for isolating and delaying uncontrollable reactions that occur upon direct contact and / or for inhibiting the degradation of easily hydrolyzed active ingredients (including but not limited to easily hydrolyzed or oxidized small molecule organic compounds, polymers / precursors, nutrients / natural products) and / or for inhibiting the reaction of easily oxidized active ingredients.

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