Stable oil-in-oil emulsions and oil-in-oil-in-oil multiple emulsions based on phosphazene derivatives and methods of making

Abstract

This invention relates to the field of colloidal interface technology and relates to a stable oil-in-oil emulsion and oil-in-oil multiple emulsion based on phosphazene derivatives and their preparation methods. The invention uses the phosphorus-nitrogen skeleton of phosphazene as the core, and obtains amphiphilic phosphazene derivatives containing alkoxy chains or fluorocarbon chains through nucleophilic substitution reactions. Utilizing the difference in polarity between the two side groups of these amphiphilic phosphazene derivatives, they exhibit characteristic affinity for two oil phase solvents, resulting in stable oil-in-oil emulsions and multiple emulsions. The method is simple and low-cost, offering better economic benefits, and solves the problem of using a single stabilizer in existing oil-in-oil emulsion technologies.

Description

Technical Field

[0001] This invention relates to the field of colloidal interface technology, and specifically discloses an oil-in-oil emulsion using phosphazene derivatives as stabilizers and its preparation method. Background Technology

[0002] Emulsions are an important component of commercial products, widely used in cosmetics, pharmaceuticals, food, and other chemical products. Composed of two or more immiscible phases, typically stabilized by molecular surfactants, polymers, proteins, and / or solid particles, emulsions are an integral part of our daily lives. Emulsions can be classified into conventional emulsions such as water-in-oil emulsions (W / O) and oil-in-water emulsions (O / W), and unconventional emulsions such as multiple emulsions (W / O / W, O / W / O, W / W / W, or O / O / O), water-in-water emulsions (W / W), and oil-in-oil emulsions (O / O). O / O emulsions are formed by two oil phases with lower dielectric constants, or by one oil phase replaced by an anhydrous phase (polar non-aqueous phase) with a higher dielectric constant.

[0003] Due to the absence of hydration, O / O emulsions lack unevenly distributed charges, resulting in the absence of a double layer for stabilization at the emulsion interface. Their stability relies solely on the steric hindrance of the stabilizer. Furthermore, compared to the interfacial tension difference between water and oil (>50 mN / m), the interfacial tension difference between two immiscible oils (<5 mN / m) is even smaller. Therefore, the surface polarity, wettability, molecular weight, and structure of the stabilizer must be strictly controlled and designed to effectively achieve interfacial stability. To date, the variety of O / O emulsion stabilizers is extremely limited. Only a very few block copolymers with specific structures and two-dimensional nanosheets (J. Am. Chem. Soc. 2016, 138, 14, 4714–4717; ACS Macro Lett. 2017, 6: 1201-6) and other nanoparticles have been studied and reported. However, these stabilizers are mostly complex in design, have cumbersome synthesis processes, and are difficult to control precisely. Therefore, developing a simple and efficient method for preparing O / O emulsion stabilizers is an urgent problem to be solved in this field, and also an important measure to effectively promote the development of this field, which will provide greater convenience and choices for related industrial production and applications.

[0004] Compared to traditional block copolymers, phosphazenes have an inorganic backbone composed of alternating P and N atoms in the form of single and double bonds. The two identical or different side chain groups attached to each P atom have a wide range of choices, allowing for modification and adjustment according to application requirements. Different side chain structures of phosphazene materials endow them with special functions and properties. In our previous work, we prepared amphiphilic polyphosphazene-stabilized fluorinated water-in-oil emulsions (CN115873170B). Therefore, to address the aforementioned issues, and leveraging the excellent properties of phosphazene materials, we have proposed simultaneously introducing hydrophilic and hydrophobic side groups into the phosphazene backbone structure to prepare brush-type amphiphilic phosphazenes, providing the possibility of using them as macromolecular emulsifiers to stabilize oil-in-oil emulsions.

[0005] This invention utilizes polymerization and nucleophilic substitution reactions to prepare amphiphilic phosphazenes with good emulsifying properties. The ether-containing and alkoxy-containing or fluorocarbon-containing side groups exhibit excellent compatibility with polar and nonpolar solutions, respectively. This allows for the construction of stable oil-in-oil emulsion systems and fluorinated multiple emulsion systems based on phosphazene derivatives. This is expected to solve the problem of water-sensitive reactions that cannot be achieved by traditional emulsions, and promote the development of water-sensitive reactions towards safer and more efficient directions. Summary of the Invention

[0006] To address the problems of the extremely limited variety of existing O / O emulsion stabilizers, the complexity of stabilizer design, the cumbersome synthesis process, and the difficulty in precise control, this invention provides an oil-in-oil emulsion and a fluorinated multiple emulsion system constructed using phosphazene derivatives, as well as their preparation methods.

[0007] To solve the above-mentioned technical problems, the present invention provides a method for preparing oil-in-oil emulsions using phosphazene derivatives, which mainly includes the following steps:

[0008] Step 1: React alcohol ethers with NaH or metallic sodium to obtain a hydrophilic side-chain sodium salt solution; react alcohols with NaH or metallic sodium to obtain a hydrophobic side-chain sodium salt solution; mix the two sodium salt solutions to obtain a mixed sodium salt solution; wherein the alcohols are alcohols without fluorine substitution or alcohols with fluorine substitution.

[0009] Step 2: Dissolve hexachlorocyclotriphosphazene or polydichlorophosphazene prepared by polymerization in an organic solvent, add dropwise to the mixed sodium salt solution of Step 1, carry out the substitution reaction, control the reaction temperature, and after complete substitution, obtain the product by rotary evaporation and membrane separation, freeze-dry or blow-dry to obtain the fully substituted amphiphilic phosphazene derivative.

[0010] Step 3: Disperse the fully substituted amphiphilic phosphazene derivative obtained in Step 2 in a polar solvent (such as N,N-dimethylformamide or acetonitrile) or a non-polar solvent (such as an alkane solvent or a perfluoroalkane solvent), and denote it as oil phase 1. Then, a certain mass of non-polar solvent or polar solvent is slowly added dropwise to oil phase 1 as oil phase 2. After stirring under mechanical conditions of 3 to 10 Kr / min for 1.5 to 30 min, an oil-in-oil emulsion stable only by the amphiphilic phosphazene derivative is formed.

[0011] Alternatively: Disperse an amphiphilic phosphazene derivative containing an alkoxy chain in a certain mass of an alkane solvent to form a mixed solution 1; disperse an amphiphilic phosphazene derivative containing a fluorocarbon chain in a certain mass of a perfluoroalkane solvent to form a mixed solution 2; add the mixed solution 1 containing the phosphazene derivative, the mixed solution 2, and a certain mass of a polar solvent as a third solvent into an ampoule, and the order is not limited. After stirring under mechanical conditions of 3-10 Kr / min for 1.5-30 min, an oil-in-oil (O / O / O) multiple emulsion stable by two different amphiphilic phosphazene derivatives is formed; the amphiphilic phosphazene derivative containing an alkoxy chain corresponds to the amphiphilic phosphazene derivative obtained in step 1 when the alcohol is not fluorinated, and the amphiphilic phosphazene derivative containing a fluorocarbon chain corresponds to the amphiphilic phosphazene derivative obtained in step 1 when the alcohol is fluorinated.

[0012] In step 1, the alcohol ether is one of ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, or polyethylene glycol monomethyl ether (Mn=200~2000); the alcohol is one of pentanol, heptanol, octanol, nonanol, decanol, dodecanol, hexadecanol, eicosanool, trifluoroethanol, tetrafluoropropanol, hexafluorobutanol, hexafluoroisopropanol, octafluoropentanol, dodecafluoroheptanol, and hexafluorodecanol, and the molar ratio of the alcohol to sodium hydride or metallic sodium is 1:1 to 3:1, and the concentration of the organic solution containing sodium hydride is 0.2 mol / L to 1.1 mol / L.

[0013] In step 2, the organic solvent is one or more of toluene, trichlorobenzene, tetrahydrofuran, and industrial hexane; the reaction temperature is 5 ℃ to 150 ℃; and the reaction time is 12 h to 96 h. The molar ratio of hexachlorocyclotriphosphazene or polydichlorophosphazene to the mixed sodium salt is 1:6 to 1:18. The molar percentage of hydrophilic side groups in the amphiphilic polyphosphazene is 5% to 95%, and the molar percentage of hydrophobic side groups in the amphiphilic polyphosphazene is 5% to 95%.

[0014] In step 3, the phosphazene derivative has a mass fraction of 1.5 wt% to 50 wt% in the oil-in-oil emulsion, preferably 2.5 wt% to 10 wt%, more preferably 5 wt%; the polar solvent N,N-dimethylformamide or acetonitrile has a mass ratio of 1 wt% to 99 wt% in the emulsion; the non-polar solvent is an alkane solvent, selected from unsubstituted alkane solvents or perfluoroalkane solvents; the unsubstituted alkane solvent is one or more of n-pentane, n-heptane, n-octane, n-decane, and n-dodecane; the perfluoroalkane solvent is one or more of perfluoropentane, perfluorohexane, perfluoroheptane, and perfluorooctane.

[0015] For oil-in-oil emulsions, the mass ratio of polar solvent to nonpolar solvent is consistent with the corresponding molar ratio of side groups.

[0016] When further preparing oil-in-oil (O / O / O) multiple emulsions, the third solvent is preferably one of acetonitrile, N,N-dimethylformamide, etc. By adjusting the ratio of mixed solution 1, mixed solution 2, and the third solvent, as well as the stirring speed, oil-in-oil (O / O / O) multiple emulsions with different contents and particle sizes can be prepared. Oil-in-oil (O / O / O) multiple emulsions consist of stable, dispersed small droplets of oil-in-oil type dispersed within a continuous liquid phase (see [reference]). Figure 6 ).

[0017] The preparation method of this invention is simple and easy to implement. The amphiphilic polyphosphazene macromolecular emulsifier not only constructs a series of carbon-containing oil-in-oil emulsions and fluorine-containing oil-in-oil emulsions, but also constructs O / O / O multi-emulsions containing both carbon and fluorine. This provides more possibilities for stabilizing oil-in-oil emulsions and is expected to solve the problem of water-sensitive reactions that cannot be achieved by traditional emulsions, thus promoting the development of water-sensitive reactions towards a safer and more efficient direction. Attached Figure Description

[0018] Figure 1 The reaction structure of the amphiphilic cyclophosphonitrile derivative in Example 1 of this invention;

[0019] Figure 2 The reaction structure of the amphiphilic polyphosphazene derivative in Example 6 of this invention;

[0020] Figure 3 The images show a visual diagram of the emulsion, an optical microscope image of the emulsion interior, and a statistical diagram of the particle size distribution in Example 1 of the present invention, wherein the average droplet size in the Octane-in-DMF emulsion is 3.18 μm.

[0021] Figure 4 The images show a visual diagram of the emulsion, an optical microscope image of the emulsion interior, and a statistical diagram of the particle size distribution in Example 6 of the present invention, wherein the average droplet size in the Octane-in-DMF emulsion is 42.77 μm.

[0022] Figure 5 The images show a visual representation of the oil-in-oil emulsion, an optical microscope image of the emulsion interior, and a statistical diagram of the particle size distribution in Example 14 of this invention. The average droplet size in the Octane-in-DMF emulsion is 41.12 μm.

[0023] Figure 6 These are a visual image and an internal optical microscope image of the multiple emulsion in Example 14 of the present invention. The emulsion type is perfluorooctane encapsulated in DMF encapsulated in n-octane. Figure 6 The lower white part on the right is the corresponding oil-in-oil (O / O / O) multiple emulsion, and the upper part is the excess solvent. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0025] Unless otherwise specified, the raw materials, reagents or apparatus used in the following examples and comparative examples are available from conventional commercial sources or can be obtained by existing known methods.

[0026] To better illustrate the present invention, further examples are provided below.

[0027] Example 1

[0028] 5 g of cyclophosphonitrile was dissolved in anhydrous tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.1896 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.0948 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for 12 h, followed by heating in an oil bath at 50 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 500 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product is a fully substituted amphiphilic cyclophosphonitrile derivative with 50% polyethylene glycol 200 monomethyl ether oxide and 50% pentanol oxide as the molar amount of the side groups.

[0029] 2.00 g of a phosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide mixture. The mixture was mechanically stirred at 8 Kr / min for 10 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which had a mass fraction of 20% and a 1:1 ratio of the two oil phases. The emulsion was an orange-yellow liquid containing uniform micron-sized droplets with an average particle size of 3.18 μm, and remained stable at room temperature for 20–25 days.

[0030] Example 2

[0031] 5 g of cyclophosphonitrile was dissolved in anhydrous tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.1517 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.1327 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for 12 h, followed by heating in an oil bath at 50 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 500 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product is a fully substituted amphiphilic cyclophosphonitrile derivative with 30% polyethylene glycol 200 monomethyl ether oxy and 70% pentanol oxy in terms of the molar amount of the side groups.

[0032] 2.00 g of a phosphazene derivative was dispersed in 2.40 g of N,N-dimethylformamide. Then, 5.60 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide mixture. The mixture was mechanically stirred at 8 Kr / min for 10 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which had a mass fraction of 20% and a two-phase ratio of 3:7. The emulsion was an orange-yellow liquid containing uniform micron-sized droplets with an average particle size of 2.81 μm, and remained stable at room temperature for 20–25 days.

[0033] Example 3

[0034] 5 g of cyclophosphonitrile was dissolved in anhydrous tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.2712 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.0133 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for 12 h, followed by heating in an oil bath at 50 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 500 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product is a fully substituted amphiphilic cyclophosphonitrile derivative with 93% polyethylene glycol 200 monomethyl ether oxy and 7% pentanol oxy in terms of the molar amount of the side groups.

[0035] 2.00 g of a phosphazene derivative was dispersed in 7.20 g of N,N-dimethylformamide. Then, 0.80 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide mixture. The mixture was mechanically stirred at 8 Kr / min for 10 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which had a mass fraction of 20% and a two-phase ratio of 9:1. The emulsion was an orange-yellow liquid containing uniform micron-sized droplets with an average particle size of 4.02 μm, and remained stable at room temperature for 20–25 days.

[0036] Example 4

[0037] 5 g of cyclophosphonitrile was dissolved in anhydrous tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.0948 mol of polyethylene glycol 400 monomethyl ether sodium salt and 0.1896 mol of n-octanol sodium salt. The reaction was carried out at room temperature for 16 h, followed by heating in an oil bath at 66 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 500 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product is a fully substituted amphiphilic cyclophosphonitrile derivative with 50% polyethylene glycol 400 monomethyl ether oxy and 50% octyl oxy groups by a molar amount of side groups.

[0038] 0.80 g of a phosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide mixture. The mixture was mechanically stirred at 10 Kr / min for 10 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, with a mass fraction of 10% and a 1:1 ratio of the two oil phases. This emulsion was a yellowish-brown liquid containing uniform micron-sized droplets with an average particle size of 5.32 μm, and remained stable at room temperature for 20–25 days.

[0039] Example 5

[0040] 5 g of cyclophosphonitrile was dissolved in anhydrous tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.0948 mol of polyethylene glycol 400 monomethyl ether sodium salt and 0.1896 mol of n-dodecyl sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 66 °C for 48 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO=500 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product is a fully substituted amphiphilic cyclophosphonitrile derivative with 50% polyethylene glycol 400 monomethyl etheroxy and 50% dodecyloxy groups by molar amount of side groups.

[0041] 0.80 g of a phosphazene derivative was dispersed in 4.00 g of acetonitrile. Then, 4.00 g of n-dodecane solution was slowly added dropwise to the acetonitrile mixture. The mixture was mechanically stirred at 10 Kr / min for 10 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which had a mass fraction of 10% and a 1:1 ratio between the two oil phases. This emulsion was a yellowish-brown liquid containing uniform micron-sized droplets with an average particle size of 5.62 μm, and remained stable at room temperature for 25–30 days.

[0042] Example 6

[0043] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1710 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.0880 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for 8 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The solution was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 51% polyethylene glycol 200 monomethyl ether oxy and 49% pentanol oxy in terms of side group molar amount.

[0044] 0.40 g of polyphosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 4 min to form an oil-in-oil emulsion stable only by the polyphosphazene derivative, in which the mass fraction of the polyphosphazene derivative was only 5%, and the ratio of the two oil phases was 1:1. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 41.77 μm, and remained stable at room temperature for more than 30 days.

[0045] Example 7

[0046] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1379 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.1206 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 30% polyethylene glycol 200 monomethyl ether oxy and 70% pentanol oxy in terms of the molar amount of the side groups.

[0047] 0.40 g of polyphosphazene derivative was dispersed in 2.40 g of N,N-dimethylformamide. Then, 5.60 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 4 min to form an oil-in-oil emulsion stable only by the polyphosphazene derivative, in which the mass fraction of the polyphosphazene derivative was only 5%, and the ratio of the two oil phases was 3:7. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 41.23 μm, and remained stable at room temperature for more than 30 days.

[0048] Example 8

[0049] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.2400 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.0170 mol of n-pentanol sodium salt. The reaction was carried out at room temperature for 8 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 91% polyethylene glycol 200 monomethyl ether oxy and 9% pentanol oxy in terms of side group molar amount.

[0050] 0.40 g of polyphosphazene derivative was dispersed in 7.20 g of N,N-dimethylformamide. Then, 0.80 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 4 min to form an oil-in-oil emulsion stable only by the polyphosphazene derivative, in which the mass fraction of the polyphosphazene derivative was only 5%, and the ratio of the two oil phases was 9:1. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 42.05 μm, and remained stable at room temperature for more than 30 days.

[0051] Example 9

[0052] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in tetrahydrofuran and then added dropwise to a mixed sodium salt consisting of 0.1710 mol of diethylene glycol monomethyl ether sodium salt and 0.0880 mol of n-octanol sodium salt. The reaction was carried out at room temperature for 6 h, followed by heating in an oil bath at 66 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 50% diethylene glycol monomethyl ether oxy and 50% octyl oxy groups by molar amount of the side groups.

[0053] 0.40 g of polyphosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of n-octane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 4 min to form an oil-in-oil emulsion stable only by the polyphosphazene derivative, in which the mass fraction of the polyphosphazene derivative was only 5%, and the ratio of the two oil phases was 1:1. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 41.83 μm, and remained stable at room temperature for more than 30 days.

[0054] Example 10

[0055] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1710 mol of polyethylene glycol 400 monomethyl ether sodium salt and 0.0880 mol of n-octanol sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 50% polyethylene glycol 400 monomethyl ether oxy and 50% octyl oxy groups by molar amount of the side groups.

[0056] 0.40 g of polyphosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of dodecane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 4 min to form an oil-in-oil emulsion stable only by the polyphosphazene derivative, in which the mass fraction of the polyphosphazene derivative was only 5%, and the ratio of the two oil phases was 1:1. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 42.01 μm, and remained stable at room temperature for more than 30 days.

[0057] Example 11

[0058] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1724 mol of polyethylene glycol 1000 monomethyl ether sodium salt and 0.0862 mol of n-hexadecyl sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO=3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 52% polyethylene glycol 1000 monomethyl ether oxy and 48% hexadecyl oxy in terms of side group molar amount.

[0059] 0.40 g of a phosphazene derivative was dispersed in 4.00 g of acetonitrile. Then, 4.00 g of n-hexadecane solution was slowly added dropwise to the acetonitrile solution. The mixture was mechanically stirred at 5 Kr / min for 5 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which accounted for only 5% of the total mass. The ratio of the two oil phases was 1:1. This emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 42.52 μm, and remained stable at room temperature for more than 30 days.

[0060] Example 12

[0061] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1724 mol of polyethylene glycol 500 monomethyl ether sodium salt and 0.0862 mol of hexafluoroisopropoxide sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator flask for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 52% polyethylene glycol 500 monomethyl ether oxy and 48% hexafluoroisopropoxide oxy in terms of side group molar amount.

[0062] 0.40 g of a phosphazene derivative was dispersed in 4.00 g of acetonitrile. Then, 4.00 g of perfluorooctane solution was slowly added dropwise to the acetonitrile solution. The mixture was mechanically stirred at 5 Kr / min for 5 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which accounted for only 5% of the total mass. The ratio of the two oil phases was 1:1. The emulsion was a pale yellow liquid containing uniform micron-sized droplets with an average particle size of 45.82 μm, and remained stable at room temperature for more than 30 days.

[0063] 0.40 g of the above-mentioned phosphazene derivative was dispersed in 4.00 g of perfluorooctane to form mixed solution 1, and 0.40 g of the polyphosphazene derivative from Example 10 was dispersed in 4.00 g of n-octane to form mixed solution 2. Mixed solutions 1 and 2 containing phosphazene derivatives were added to an ampoule, the order of which is not limited. After mechanical stirring at 5 Kr / min for 5 min, an O / O / O multiple emulsion stable by the two phosphazene derivatives was formed, with the ratio of the three oil phases—perfluorooctane, acetonitrile, and n-octane—being 1:2:1. This emulsion was a pale yellow liquid, exhibiting micron-sized droplets with a dual interface, and remained stable at room temperature for more than 10 days.

[0064] Example 13

[0065] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1724 mol of polyethylene glycol 200 monomethyl ether sodium salt and 0.0862 mol of trifluoroethoxy sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO = 3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 52% polyethylene glycol 200 monomethyl ether oxy and 48% trifluoroethoxy oxy groups by molar amount of the side groups.

[0066] 0.40 g of a phosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of perfluoropentane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 5 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which accounted for only 5% of the total mass. The ratio of the two oil phases was 1:1. The emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 45.40 μm, and remained stable at room temperature for more than 30 days.

[0067] 0.40 g of the above-mentioned phosphazene derivative was dispersed in 4.00 g of perfluoropentane to form mixed solution 1, and 0.40 g of the polyphosphazene derivative from Example 6 was dispersed in 4.00 g of n-octane to form mixed solution 2. Mixed solutions 1 and 2 containing phosphazene derivatives, along with 8.00 g of N,N-dimethylformamide, were added to an ampoule in any order. The mixture was mechanically stirred at 10 Kr / min for 8 min to form an O / O / O multiple emulsion stable by the two phosphazene derivatives. The ratio of the three oil phases—perfluoropentane, N,N-dimethylformamide, and n-octane—was 1:2:1. This emulsion was a pale yellow liquid with micron-sized droplets forming a dual-interface structure and remained stable at room temperature for more than 10 days.

[0068] Example 14

[0069] 10 g of linear polydichlorophosphazene was prepared by polymerization. The linear polydichlorophosphazene was dissolved in xylene and then added dropwise to a mixed sodium salt consisting of 0.1724 mol of diethylene glycol monomethyl ether sodium salt and 0.0862 mol of octafluoropentanol sodium salt. The reaction was carried out at room temperature for ≥12 h, followed by heating in an oil bath at 110 °C for 24 h. After the reaction was completed, the product solution was cooled and transferred to a rotary evaporator for rotary evaporation. After rotary evaporation, the product was dissolved in an appropriate amount of methanol solution and transferred to a dialysis bag (MWCO=3000 kDa). The product was dialyzed five times with methanol and deionized water. The resulting product solution was evaporated to dryness to obtain the crude product. Finally, the crude product was dried to constant weight in a vacuum oven at 70 °C. The obtained product was a fully substituted amphiphilic polyphosphazene product with 51% diethylene glycol monomethyl ether oxy and 49% octafluoropentanol oxy in terms of side group molar amount.

[0070] 0.40 g of a phosphazene derivative was dispersed in 4.00 g of N,N-dimethylformamide. Then, 4.00 g of perfluorooctane solution was slowly added dropwise to the N,N-dimethylformamide solution. The mixture was mechanically stirred at 5 Kr / min for 5 min to form an oil-in-oil emulsion stable only by the phosphazene derivative, which accounted for only 5% of the total mass. The ratio of the two oil phases was 1:1. This emulsion was a milky white liquid containing uniform micron-sized droplets with an average particle size of 45.12 μm, and remained stable at room temperature for more than 30 days.

[0071] 0.40 g of the above-mentioned phosphazene derivative was dispersed in 4.00 g of perfluorooctane to form mixed solution 1, and 0.40 g of the polyphosphazene derivative from Example 9 was dispersed in 4.00 g of n-octane to form mixed solution 2. Mixed solutions 1 and 2 containing phosphazene derivatives, along with 8.00 g of N,N-dimethylformamide, were added to an ampoule in any order. The mixture was mechanically stirred at 10 Kr / min for 8 min to form an O / O / O multiple emulsion stable by the two phosphazene derivatives, with the ratio of the three oil phases—perfluorooctane, N,N-dimethylformamide, and n-octane—being 1:2:1. This emulsion was a pale yellow liquid with micron-sized droplets forming a dual-interface structure and remained stable at room temperature for more than 10 days.

[0072] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing stable oil-in-oil emulsions and oil-in-oil-in-oil multiple emulsions based on phosphazene derivatives, characterized in that, Includes the following steps: Step 1: React alcohol ethers with NaH or metallic sodium to obtain a hydrophilic side-chain sodium salt solution; react alcohols with NaH or metallic sodium to obtain a hydrophobic side-chain sodium salt solution; mix the two sodium salt solutions to obtain a mixed sodium salt solution; wherein the alcohols are alcohols without fluorine substitution or alcohols with fluorine substitution. Step 2: Dissolve hexachlorocyclotriphosphazene or polydichlorophosphazene prepared by polymerization in an organic solvent, add dropwise to the mixed sodium salt solution of Step 1, carry out the substitution reaction, control the reaction temperature, and after complete substitution, obtain the product by rotary evaporation and membrane separation, freeze-dry or blow-dry to obtain the fully substituted amphiphilic phosphazene derivative. Step 3: Disperse the fully substituted amphiphilic phosphazene derivative obtained in Step 2 in a polar solvent or a non-polar solvent (referred to as oil phase 1). Then, slowly add a certain mass of non-polar solvent or polar solvent as oil phase 2 to oil phase 1. After stirring under mechanical conditions of 3 to 10 Kr / min for 1.5 to 30 min, an oil-in-oil emulsion stable only by the amphiphilic phosphazene derivative is formed. Alternatively, in step 3: a mixed solution 1 is formed by dispersing an amphiphilic phosphazene derivative containing an alkoxy chain in a certain mass of an alkane solvent; a mixed solution 2 is formed by dispersing an amphiphilic phosphazene derivative containing a fluorocarbon chain in a certain mass of a perfluoroalkane solvent; the mixed solution 1 and mixed solution 2 containing phosphazene derivatives, along with a certain mass of a polar solvent, are added to an ampoule as a third solvent, and the order is not limited. After stirring under mechanical conditions of 3–10 Kr / min for 1.5–30 min, an oil-in-oil (O / O / O) multiple emulsion stable by two different amphiphilic phosphazene derivatives is formed. The amphiphilic phosphazene derivatives containing alkoxy chains are the amphiphilic phosphazene derivatives obtained when the alcohol in step 1 is not fluorinated, while the amphiphilic phosphazene derivatives containing fluorocarbon chains are the amphiphilic phosphazene derivatives obtained when the alcohol in step 1 is fluorinated.

2. The method according to claim 1, characterized in that, In step 1, the alcohol ether is one of ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, or polyethylene glycol monomethyl ether with a molecular weight Mn of 200-2000; the alcohol is one of pentanol, heptanol, octanol, nonanol, decanol, dodecanol, hexadecanol, eicosanool, trifluoroethanol, tetrafluoropropanol, hexafluorobutanol, hexafluoroisopropanol, octafluoropentanol, dodecafluoroheptanol, and hexafluorodecanol.

3. The method according to claim 1, characterized in that, The molar ratio of alcohol ethers or alcohols to sodium hydride or metallic sodium is 1:1 to 3:1, and the concentration of the organic solution containing sodium hydride is 0.2 mol / L to 1.1 mol / L.

4. The method according to claim 1, characterized in that, In step 2, the organic solvent is one or more of toluene, trichlorobenzene, tetrahydrofuran, and industrial hexane; the reaction temperature is 5℃~150℃; and the reaction time is 12 h~96 h. The molar ratio of hexachlorocyclotriphosphazene or polydichlorophosphazene to the mixed sodium salt is 1:6~1:

18.

5. The method according to claim 1, characterized in that, The hydrophilic side group accounts for 5% to 95% of the molar percentage of the amphiphilic polyphosphazene, and the hydrophobic side group accounts for 5% to 95% of the molar percentage of the amphiphilic polyphosphazene.

6. The method according to claim 1, characterized in that, In step 3, the preferred mass fraction is 2.5wt% to 10wt%, more preferably 5wt%; the polar solvent N,N-dimethylformamide or acetonitrile has a mass ratio of 1w% to 99w in the emulsion, and the non-polar solvent is an alkane solvent, selected from unsubstituted alkane solvents or perfluoroalkane solvents.

7. The method according to claim 6, characterized in that, The unsubstituted alkane solvent is one or more of n-pentane, n-heptane, n-octane, n-decane, and n-dodecane; the perfluoroalkane solvent is one or more of perfluoropentane, perfluorohexane, perfluoroheptane, and perfluorooctane.

8. The method according to claim 1, characterized in that, For oil-in-oil emulsions, the mass ratio of polar solvent to nonpolar solvent is consistent with the corresponding molar ratio of side groups.

9. The method according to claim 1, characterized in that, In step 3, when preparing oil-in-oil (O / O / O) multiple emulsions, the third solvent is preferably one of acetonitrile, N,N-dimethylformamide, etc.; by adjusting the ratio of mixed solution 1, mixed solution 2, and the third solvent, as well as the stirring speed, oil-in-oil (O / O / O) multiple emulsions with different contents and particle sizes can be prepared.

10. Stable oil-in-oil emulsions and oil-in-oil-in-oil multiple emulsions based on phosphazene derivatives prepared by the method according to any one of claims 1-9.

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