Multi - non - covalent - bond - enhanced pH / glucose - responsive Pickering emulsions, preparation and applications

Abstract

The present invention discloses a multiple non-covalent bond enhanced pH / glucose-responsive Pickering emulsion, its preparation and application, which relates to the technical field of Pickering emulsions. The preparation method of the Pickering emulsion comprises the following steps: S1: reacting 3-aminophenylboronic acid hydrochloride, sodium alginate and cyclohexyl isocyanide to obtain a phenylboronic acid-based sodium alginate derivative; S2: adding diacylated anthocyanins from purple sweet potato to soy protein isolate after hydration and degradation treatment, and mixing them to obtain soy protein isolate-diacylated anthocyanins from purple sweet potato; S3: ultrasonically mixing the phenylboronic acid-based sodium alginate derivative and soy protein isolate-diacylated anthocyanins from purple sweet potato, and then homogenizing with squalene to obtain the Pickering emulsion. The Pickering emulsion of the present invention, as a supramolecular hierarchical stimulus-responsive Pickering emulsion system for targeted delivery systems, not only provides new ideas for the delivery of biofunctional compounds, enhances the corresponding bioavailability, but also builds a bridge between colloid interface chemistry and drug delivery systems.

Description

Technical Field

[0001] The present invention relates to the technical field of Pickering emulsions, and particularly to multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsions, preparation and applications thereof. Background Art

[0002] Purple sweet potato diacylated anthocyanins (PSPAs) are a type of anthocyanins (ACN) in purple sweet potato anthocyanins, belonging to natural polyphenolic compounds, and having pharmacological effects such as antioxidant, anti-inflammatory and anti-diabetic effects. PSPAs have great potential in reducing postprandial blood glucose because they have excellent inhibitory effects on α-glucosidase (α-G) in the intestine. However, since they will be destroyed by gastric acid and pepsin in the gastric juice environment when passing through the stomach, targeted delivery of PSPAs is a formidable challenge. Summary of the Invention

[0003] Based on the technical problems existing in the background art, the present invention proposes multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsions, preparation and applications thereof. The supramolecular hierarchical stimulus-responsive Pickering emulsion system as a targeted delivery system not only provides new ideas for the delivery of biofunctional compounds, enhances the corresponding bioavailability, but also builds a bridge between colloid interface chemistry and drug delivery systems.

[0004] The preparation method of the multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion proposed by the present invention comprises the following method steps:

[0005] S1: Preparation of phenylboronic acid-based sodium alginate derivatives

[0006] Prepared by reacting 3-aminophenylboronic acid hydrochloride, sodium alginate and cyclohexyl isocyanide as raw materials;

[0007] S2: Preparation of soy protein isolate-purple sweet potato diacylated anthocyanins

[0008] After soy protein isolate is hydrated and degraded, purple sweet potato diacylated anthocyanins are added for mixing to obtain soy protein isolate-purple sweet potato diacylated anthocyanins;

[0009] S3: Preparation of Pickering emulsions

[0010] The phenylboronic acid-based sodium alginate derivatives and soy protein isolate-purple sweet potato diacylated anthocyanins are ultrasonically mixed, and then homogenized with squalene in a high-speed homogenizer to obtain Pickering emulsions.

[0011] Preferably, the preparation method steps of the phenylboronic acid-based sodium alginate derivatives are as follows:

[0012] S11: Add formaldehyde to the aqueous solution of 3-aminophenylboronic acid hydrochloride for Schiff base reaction;

[0013] S12: Add aqueous sodium alginate solution and cyclohexyl isocyanide to the reacted solution in sequence for reaction. After reaction, perform dialysis and freeze-drying to obtain phenylboronic acid-based sodium alginate derivative.

[0014] Preferably, the mass-volume ratio of sodium alginate, 3-aminophenylboronic acid hydrochloride, formaldehyde, and cyclohexyl isocyanide is 100 g: 4 - 8 g: 1 - 5 mL: 1 - 10 mL.

[0015] Preferably, the temperature of the Schiff base reaction in S11 is 20 - 30 °C, and the time is 2 - 4 h.

[0016] Preferably, the temperature of the reaction in S12 is 20 - 30 °C, and the light-shielded reaction time is 12 - 24 h.

[0017] Preferably, the mass ratio of soy protein isolate to diacylated anthocyanins from purple sweet potato in S2 is 15 - 25:1.

[0018] Preferably, the mass ratio of phenylboronic acid-based sodium alginate derivative to soy protein isolate is 1:0.8 - 1.2.

[0019] The multiple non-covalent bond enhanced pH / glucose-responsive Pickering emulsion prepared by the above method proposed by the present invention.

[0020] The application of the multiple non-covalent bond enhanced pH / glucose-responsive Pickering emulsion proposed by the present invention in the preparation of drugs for intestinal delivery of diacylated anthocyanins.

[0021] The beneficial technical effects of the present invention:

[0022] The present invention designs a hierarchical polysaccharide / protein / polyphenol ternary complex, introduces a glucose-responsive phenylboronic acid structure in molecular design, and can regulate the interfacial microstructure; the emulsion of the present invention enhances the strength of the interfacial particle film and can maintain its structural integrity in the gastric environment; the PSPAs in the emulsion of the present invention can target and transfer to the intestine completely, have a good inhibitory effect on α-glucosidase (α-G), and improve the bioavailability of PSPAs. Description of the Drawings

[0023] Figure 1Appearance photos and particle size distribution diagrams of different substances proposed by the present invention; where a1 is the appearance photo of SA-PBA, a2 is the appearance photo of SA-PBA@SPI, a3 is the appearance photo of SA-PBA@SPI-PSPAs-1, b1 is the particle size distribution diagram of SA-PBA, b2 is the particle size distribution diagram of SA-PBA@SPI, and b3 is the particle size distribution diagram of SA-PBA@SPI-PSPAs-1;

[0024] Figure 2 Test diagrams of the emulsion proposed by the present invention; where (a) is the stability characteristic of the emulsion, (b) is the apparent viscosity of the emulsion, (c) is the strain sweep measurement of the emulsion at 1 Hz, and (d) is the angular frequency sweep measurement of the emulsion at a strain of 1%;

[0025] Figure 3 Microscopic and model diagrams of the simulated digestion of SA-PBA@SPI-PSPAs-1 emulsion proposed by the present invention; where a1 is the microscopic diagram of simulated digestion under the oral cavity, a2 is the microscopic diagram of simulated digestion under gastric juice, a3 is the microscopic diagram of simulated digestion in the intestine for 1 hour, a4 is the microscopic diagram of simulated digestion in the intestine for 2 hours, b1 is the model diagram of simulated digestion in the original state, b2 is the model diagram of simulated digestion under the oral cavity, b3 is the model diagram of simulated digestion under the stomach, b4 is the model diagram of simulated digestion in the intestine for 1 hour, and b5 is the model diagram of simulated digestion in the intestine for 2 hours;

[0026] Figure 4 Inhibition rates of different substances proposed by the present invention on α-glucosidase; where (a) is acarbose, (b) is aqueous solution of purple sweet potato diacylated anthocyanins, and (c) is SA-PBA@SPI-PSPAs-1 emulsion. Detailed implementation modes

[0027] The present invention will be further explained below in conjunction with specific embodiments.

[0028] Purple sweet potato diacylated anthocyanins were purchased from Chengdu Caoyuan Kang Biotechnology Co., Ltd., sodium alginate (SA, Cp, viscosity (200±20) mPa·s); cyclohexyl isocyanide, deuterium oxide, formaldehyde, sodium hydroxide, hydrochloric acid, anhydrous calcium chloride, and squalene were purchased from Aladdin Chemical Reagent Co., Ltd. (Shanghai, China); soy protein isolate (SPI), artificial saliva of porcine mucosa, and pepsin were provided by Shanghai Yuanye Biotechnology Co., Ltd.; porcine bile extract and porcine lipase were purchased from Hefei Bomei Biotechnology Co., Ltd.

[0029] For cell culture experiments, human L929 cells were obtained from the Cell Bank of the Chinese Academy of Sciences in Shanghai, China; DMEM and fetal bovine serum (FBS) were provided by BI (Israel Bio-Industries); the CCK-8 kit was from Dojindo, Japan; trypsin, phosphate-buffered saline (PBS), and penicillin-streptomycin mixture (5000 U / ml) were purchased from Gibco cell culture products company (Thermo Fisher Scientific, USA); α-glucosidase inhibitor (α-G), acarbose, and sodium carbonate (Na2CO3) were all from Shanghai Yuanye Bio-Technology Co., Ltd.

[0030] All reagents used in this study were of analytical grade and did not require additional purification; for all experimental procedures, MilliQ water with a resistivity of 18.2 MΩ·cm at 25 °C was used. Example 1

[0031] First, 6.00 grams of sodium alginate (SA) was weighed and then dissolved in 300 ml of deionized water to prepare a 2 wt% stock solution. Then, the pH value of the sodium alginate solution was adjusted to 3.6 using 1 M hydrochloric acid solution. At the same time, 0.33 grams of 3-aminophenylboronic acid hydrochloride (3-APBA) was weighed and dissolved in 20 ml of deionized water. Subsequently, 0.075 ml of formaldehyde was added to the 3-APBA solution, and the reaction was stirred at room temperature for three hours to ensure complete Schiff base reaction. Then, the formaldehyde-containing 3-APBA solution was added to the sodium alginate stock solution with a pH value of 3.6 and stirred vigorously for half an hour. Then, 0.33 ml of cyclohexyl isocyanide was added to the reaction mixture, and the reaction was carried out in the dark at room temperature for 24 hours. Finally, the reaction product was dialyzed and refined in deionized water through a 3500 Da dialysis bag for five days, and the dialysis fluid was changed every eight hours. The final step was to lyophilize the material to obtain the purified phenylboronic acid-based sodium alginate derivative, denoted as SA-PBA-1, with a yield of 4.45 grams.

[0032] Weigh and dissolve the SPI solution at 2 mg / ml in 0.01 mol / L phosphate buffer (pH 6.9), stir it with a magnetic stirrer at room temperature for two hours, then store the solution at 4 °C overnight to ensure complete hydration of the protein. Next, adjust the pH value of the SPI solution to 9.0 using 0.5 M NaOH, and then degrade the protein by heating at 120 °C for 20 minutes. After degradation, cool the solution to room temperature in an ice bath, adjust the pH value to 7.0 using 0.1 M HCl, and finally store it refrigerated. The next step is to dissolve PSPAs in the SPI solution at 2 mg / ml at room temperature, control the mass ratio of SPI to PSPAs to be 20:1, stir gently and keep it for 24 hours to obtain the product denoted as SPI-PSPAs-1.

[0033] Ultrasonically mix 2 g of SA-PBA-1 and 0.2 wt% SPI-PSPAs-1 as the aqueous phase, control the mass ratio of SA-PBA-1 to SPI to be 1:1, use squalene as the oil phase, mix them in a ratio of 7:3 of the oil phase to the aqueous phase into the same container, and shear for 5 minutes at a speed of 16,000 rpm using a high-speed homogenizer (T18, IKA, Germany) to obtain an emulsion, denoted as SA-PBA@SPI-PSPAs-1 emulsion. Example 2

[0034] First, weigh 5.00 grams of sodium alginate (SA), then dissolve it in 300 ml of deionized water to prepare a 2 wt% stock solution. Next, adjust the pH value of the sodium alginate solution to 3.6 using 1 M hydrochloric acid solution. Meanwhile, weigh 0.33 grams of 3-aminophenylboronic acid hydrochloride (3-APBA), dissolve it in 20 ml of deionized water. Subsequently, add 0.075 ml of formaldehyde to the 3-APBA solution and stir and react at room temperature for 2 hours to ensure complete Schiff base reaction. Then, add the formaldehyde-containing 3-APBA solution to the sodium alginate stock solution with a pH value of 3.6 and stir vigorously for half an hour. Then, add 0.33 ml of cyclohexyl isocyanide to the reaction mixture and react in the dark at room temperature for 24 hours. Finally, dialyze the reaction product through a dialysis bag with a molecular weight cut-off of 3500 Da in deionized water for five days, changing the dialysis fluid every eight hours. The final step is to lyophilize this material to obtain the purified phenylboronic acid-based sodium alginate derivative, denoted as SA-PBA-2, with a yield of 4.13 grams.

[0035] Weigh and dissolve the SPI solution at 2 mg / ml in 0.01 mol / L phosphate buffer (pH 6.9), stir it with a magnetic stirrer at room temperature for 1 hour, then store the solution at 4 °C overnight to ensure complete hydration of the protein. Next, adjust the pH value of the SPI solution to 9.0 using 0.5 M NaOH, and then degrade the protein by heating at 120 °C for 20 minutes. After degradation, cool the solution to room temperature in an ice bath, adjust the pH value to 7.0 using 0.1 M HCl, and finally store it refrigerated. The next step is to dissolve PSPAs in the SPI solution at 2 mg / ml at room temperature, control the mass ratio of SPI to PSPAs to be 15:1, stir gently and keep for 24 hours, and the obtained product is denoted as SPI-PSPAs-2.

[0036] Ultrasonically mix 2 g of SA-PBA-2 and 0.2 wt% SPI-PSPAs-2 as the aqueous phase, control the mass ratio of SA-PBA-2 to SPI to be 1:0.8, use squalene as the oil phase, mix them in a 7:3 ratio of oil phase to aqueous phase into the same container, and shear for 5 minutes at a speed of 16,000 rpm using a high-speed homogenizer (T18, IKA, Germany) to obtain an emulsion, denoted as SA-PBA@SPI-PSPAs-2 emulsion. Example 3

[0037] First, weigh 6.00 grams of sodium alginate (SA), then dissolve it in 300 ml of deionized water to prepare a 2 wt% stock solution. Next, adjust the pH value of the sodium alginate solution to 3.6 using 1 M hydrochloric acid solution. At the same time, weigh 0.33 grams of 3-aminophenylboronic acid hydrochloride (3-APBA), dissolve it in 20 ml of deionized water. Subsequently, add 0.075 ml of formaldehyde to the 3-APBA solution and stir and react at room temperature for three hours to ensure complete Schiff base reaction. Then, add the 3-APBA solution containing formaldehyde to the sodium alginate stock solution with a pH value of 3.6 and stir vigorously for half an hour. Then, add 0.20 ml of cyclohexyl isocyanide to the reaction mixture and react in the dark at room temperature for 12 hours. Finally, dialyze the reaction product through a 3500 Da dialysis bag in deionized water for five days, changing the dialysis fluid every eight hours. The final step is to lyophilize this material to obtain the purified sodium alginate derivative with phenylboronic acid groups, denoted as SA-PBA-3, with a yield of 3.51 grams.

[0038] Weigh and dissolve 2 mg / ml of SPI solution in 0.01 mol / L phosphate buffer (pH 6.9), stir for two hours at room temperature using magnetic stirring, then store the solution at 4 °C overnight to ensure complete hydration of the protein. Next, adjust the pH value of the SPI solution to 9.0 using 0.5 M NaOH, and then degrade the protein by heating at 120 °C for 20 minutes. After degradation, cool the solution to room temperature in an ice bath, adjust the pH value to 7.0 using 0.1 M HCl, and finally store it refrigerated. The next step is to dissolve PSPAs in 2 mg / ml of SPI solution at room temperature, control the mass ratio of SPI to PSPAs to be 25:1, stir gently and maintain for 24 hours, and the resulting product is denoted as SPI-PSPAs-3.

[0039] Ultrasonically mix 2 g of SA-PBA-3 and 0.2 wt% SPI-PSPAs-3 as the aqueous phase, control the mass ratio of SA-PBA-3 to SPI to be 1:1.2, use squalene as the oil phase, mix them in a 7:3 ratio of oil phase to aqueous phase into the same container, and shear for 5 minutes at a speed of 16000 rpm using a high-speed homogenizer (T18, IKA, Germany) to obtain an emulsion, denoted as SA-PBA@SPI-PSPAs-3 emulsion. Comparative Example 1

[0040] Use 0.2 wt% SA-PBA-1 as the aqueous phase, squalene as the oil phase, mix them in a 7:3 ratio of oil phase to aqueous phase into the same container, and shear for 5 minutes at a speed of 16000 rpm using a high-speed homogenizer (T18, IKA, Germany) to obtain an emulsion, denoted as SA-PBA emulsion. Comparative Example 2

[0041] Weigh and dissolve 2 mg / ml of SPI powder in 0.01 mol / L phosphate buffer (pH 6.9), stir for two hours at room temperature using magnetic stirring, then store the solution at 4 °C overnight to ensure complete hydration of the protein. Next, adjust the pH value of the SPI solution to 9.0 using 0.5 M NaOH, and then degrade the protein by heating at 120 °C for 20 minutes. After degradation, cool the solution to room temperature in an ice bath, adjust the pH value to 7.0 using 0.1 M HCl, and finally store it refrigerated, denoted as SPI-1 solution.

[0042] 2 g of SA-PBA-1 and 0.2 wt% SPI-1 solution were ultrasonically mixed as the aqueous phase, with the mass ratio of SA-PBA-1 to SPI controlled at 1:1. Squalene was used as the oil phase and was mixed with the aqueous phase in a 7:3 ratio in the same container. An emulsion was obtained by shearing at 16,000 rpm for 5 minutes using a high-speed homogenizer (T18, IKA, Germany), denoted as SA-PBA@SPI emulsion.

[0043] Figure 1 Photographs of the appearance, optical microscope images (20 μm), and emulsion particle size distribution diagrams of the emulsions prepared in Comparative Example 1, Comparative Example 2, and Example 1. Figure 1 It can be seen that the emulsion without PSPAs was milky white and showed a rheological inversion phenomenon, while the emulsion with PSPAs was purplish red and transformed into a gel during inversion. By observing the emulsion with an optical microscope and measuring the particle size using ImageJ, it was found that the emulsion containing only SA-PBA had the largest particle size, approximately 45 μm; after adding SA-PBA@SPI, the particle size of the emulsion decreased to approximately 18 μm. The emulsion with SA-PBA@SPI-PSPAs showed the smallest particle size, approximately 15 μm. These results indicate that SA-PBA, SA-PBA@SPI, and SA-PBA@SPI-PSPAs all have excellent amphiphilic affinity.

[0044] The TSI value is an accurate indicator of emulsion stability, and a higher TSI value corresponds to weaker stability. Figure 2 Part (a) shows the change in the TSI value of the SA-PBA@SPI-stabilized emulsion within 6 hours with and without the addition of PSPAs. The results show that over time, the TSI values of all emulsions increased, reflecting a gradual decrease in stability. Specifically, the initial TSI value of the SA-PBA emulsion was approximately 10, decreased to approximately 6 after adding SPI, and further decreased to approximately 2 after adding PSPAs. This indicates that the introduction of PSPAs significantly reduced the TSI value, thereby enhancing the stability of the emulsion. The improvement in stability is mainly attributed to the self-assembly of SA-PBA into soft colloidal particles and the formation of a cross-linked three-dimensional network with SPI@PSPAs, which jointly stabilized the Pickering emulsion.

[0045] The rheological properties of the emulsion are crucial for evaluating its stability, and the interfacial rheology is affected by interfacial adsorption and molecular interactions. Figure 2Part (b) shows the relationship between the apparent viscosity of the emulsion after the addition of PSPAs and the shear rate. It can be observed that the viscosity of the emulsion decreases with increasing shear rate, which indicates that the interaction between the droplet particles is weakened and the emulsion exhibits obvious shear thinning behavior. This shows that the emulsion behaves as a pseudoplastic fluid. At the same shear rate, the viscosity of the SA-PBA@SPI-PSPAs-1 emulsion is significantly higher than that of the other two formulations that also contain PSPAs. This is mainly because the addition of PSPAs strengthens the interaction between the components, thereby hindering the movement and aggregation of the droplet particles. The reduction in the migration and flow of the droplet particles leads to a higher apparent viscosity of the emulsion. The results show that the viscosity of the SA-PBA emulsion is the lowest, while the viscosity of the SA-PBA@SPI-PSPAs-1 emulsion is the highest. Figure 2 Parts (c) and (d) of the graph show the test results of strain sweep and frequency sweep. The linear viscoelastic region (LVR) was determined by strain sweep, in which the storage modulus (G') was significantly greater than the loss modulus (G''), indicating that the emulsion system exhibited obvious elastic gel behavior. The test results showed that the strain amplitude for defining the LVR was 1% before the angular frequency sweep was performed. Within the range of the angular frequency sweep test, the G' of the emulsion was always much greater than the G'', further confirming the good elastic properties of the emulsion. When PSPAs were added, both the storage modulus (G') and the loss modulus (G'') of the emulsion increased, indicating that PSPAs help to form a more compact interfacial layer at the oil-water interface, thereby effectively inhibiting the migration of droplet-like particles and enhancing the stability of the emulsion, thereby improving the viscoelasticity of the emulsion.

[0046] In order to study the digestion behavior of the emulsion, the morphological changes of the emulsion were observed by optical microscopy. Figure 3 Part (a) shows a schematic diagram of the in vitro gastrointestinal digestion of SA-PBA@SPI-PSPAs-1 emulsion. Figure 3Part (b) shows a model diagram of the simulated digestion of SA-PBA@SPI-PSPAs-1 emulsion. Initially, after 5 minutes of digestion in simulated oral fluid, the morphology of the emulsion droplets was similar to that of the original droplets, and the size of the droplets did not change significantly. This is because the simulation in the oral phase only lasted for 5 minutes, which was too short to cause obvious emulsification decomposition. Next, after 1 hour of digestion in simulated gastric fluid, the morphology of the droplets was still similar to that of normal droplets, but the size of the droplets increased slightly. Nevertheless, the emulsion remained relatively stable, which can be attributed to the pKa value of SA-PBA being 7.4, while the pH value of simulated gastric fluid was 2.5. At this acidic pH value, below the pKa, SA-PBA tended to form an acidic gel, thus enhancing the stability of the emulsion. Finally, after 1 hour of digestion in simulated intestinal fluid, obvious emulsification decomposition occurred, and after 2 hours, the emulsion was completely decomposed. This was due to the neutral pH value of intestinal fluid (about pH 7.0), which was close to the pKa value of sodium alginate, resulting in complete emulsification decomposition and promoting the release of PSPAs in the intestine.

[0047] We compared the inhibitory effects of PSPAs aqueous solution (a solution with PSPAs dissolved in water) and SA-PBA@SPI-PSPAs-1 emulsion on α-glucosidase (α-G). As Figure 4 shown, the inhibitor concentration was positively correlated with the inhibitory effect on α-G and showed a dose-dependent relationship. Specifically, the IC50 value of the PSPAs emulsion was lower than that of the PSPAs aqueous solution and was close to the IC50 value of acarbose, indicating that the PSPAs emulsion had a stronger inhibitory effect on α-G, while the inhibitory effect of the PSPAs aqueous solution was similar to that of acarbose. This difference can be attributed to the fact that PSPAs, as polyphenolic compounds in aqueous solution, usually inhibit α-G through non-competitive inhibition. They do not directly bind to the active site of the enzyme, but interact with other regions or the auxiliary structure of the enzyme, causing conformational changes or altering the stability of the enzyme, thereby reducing its activity. In contrast, some PSPAs in the PSPAs emulsion bind to SPI to form quinone compounds, and these quinone compounds can directly interact with the active site of α-G to form an enzyme-inhibitor complex, directly preventing the enzyme from binding to the substrate, or further altering the conformation of the enzyme, thereby reducing its catalytic efficiency.

[0048] Although the embodiments of the present application have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present application. The scope of the present application is defined by the appended claims and their equivalents and should be included within the protection scope of the present application.

Claims

1. A method for preparing a multiple non-covalent bond enhanced pH glucose response Pickering emulsion, characterized in that: The steps are as follows: S1: Preparation of phenylboronic acid-based sodium alginate derivatives S11: adding formaldehyde to an aqueous solution of 3-aminophenylborate hydrochloride to perform a Schiff base reaction; S12: adding sodium alginate aqueous solution and cyclohexyl isonitrile to the solution after the reaction in sequence to react, and dialyzing and freeze-drying after the reaction to obtain a phenylboronic acid-based sodium alginate derivative; S2: Preparation of soy protein isolate-purple sweet potato diacylated anthocyanins After the soy protein isolate is hydrated and degraded, it is added with purple sweet potato diacylated anthocyanidin and mixed to prepare soy protein isolate-purple sweet potato diacylated anthocyanidin; S3: Preparation of Pickering emulsion The phenylboronic acid-based sodium alginate derivative and the isolated soybean protein-purple sweet potato diacylated anthocyanidin were ultrasonically mixed, and then added into a high-speed homogenizer with squalene for homogenization to prepare a Pickering emulsion.

2. The method for preparing the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 1, characterized in that: The mass volume ratio of sodium alginate, 3-aminophenylborate hydrochloride, formaldehyde and cyclohexyl isocyanide is 100g:4-8g:5-10mL:1-10mL.

3. The method for preparing the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 1, characterized in that: The temperature of the Schiff base reaction in S11 is 30°C and the reaction time is 24 h.

4. The method for preparing the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 1, characterized in that: The reaction temperature in S12 is 30°C and the reaction time is 24 hours in the dark.

5. The method for preparing the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 1, characterized in that: The mass ratio of soy protein isolate to purple sweet potato diacylated anthocyanidins in S2 is 15-25:

1.

6. The method for preparing the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 1, characterized in that: The mass ratio of phenylboronic acid-based sodium alginate derivative to soy protein isolate-purple sweet potato diacylated anthocyanidins is 1:0.8-1.

2.

7. A multiple non-covalent bond enhanced pH glucose response Pickering emulsion, characterized in that: The method is prepared by any one of claims 1 to 6.

8. Use of the multiple non-covalent bond enhanced pH glucose response Pickering emulsion according to claim 7 in the preparation of drugs for intestinal delivery of diacylated anthocyanidins.

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