Multiple non-covalent bond enhanced pH / glucose response Pickering emulsion, preparation and application

Abstract

The invention discloses a multiple non-covalent bond enhanced pH / glucose response Pickering emulsion, preparation and application, and relates to the technical field of Pickering emulsions.The preparation method of the Pickering emulsion comprises the following steps that S1, 3-aminophenylboronic acid hydrochloride, sodium alginate and cyclohexyl isocyanide react to prepare a phenylboronic acid sodium alginate derivative; s2, after the soybean protein isolate is subjected to hydration and degradation treatment, the purple sweet potato diacylated anthocyanin is added for mixing, and soybean protein isolate-purple sweet potato diacylated anthocyanin is prepared; and S3, carrying out ultrasonic mixing on the phenylboronic acid sodium alginate derivative and the soybean protein isolate-purple sweet potato diacylated anthocyanin, and then homogenizing with squalene to prepare the Pickering emulsion. The Pickering emulsion disclosed by the invention is used as a supramolecular hierarchical stimulation response Pickering emulsion system of a targeted delivery system, a new thought is provided for delivery of biological functional compounds, the corresponding bioavailability is enhanced, and a bridge is erected between colloid interface chemistry and a drug delivery system.

Description

Technical Field

[0001] The invention relates to the technical field of Pickering emulsions, in particular to a multiple non-covalent bond enhanced pH / glucose response Pickering emulsion, and its preparation and application. Background Art

[0002] Purple sweet potato diacylated anthocyanidins (PSPAs) are a type of anthocyanidins (ACN) in purple sweet potato anthocyanidins. They are natural polyphenolic compounds with pharmacological effects such as antioxidant, anti-inflammatory and anti-diabetic. PSPAs have great potential in lowering postprandial blood sugar because they have excellent inhibitory effects on α-glucosidase (α-G) in the intestine. However, since they are destroyed by gastric acid and pepsin in the gastric juice environment when passing through the stomach, targeted delivery of PSPAs is a daunting challenge. Summary of the invention

[0003] Based on the technical problems existing in the background technology, the present invention proposes multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsions, preparation and application. The supramolecular hierarchical stimulus responsive Pickering emulsion system as a targeted delivery system not only provides a new idea for the delivery of biological functional compounds and enhances the corresponding bioavailability, but also builds a bridge between colloidal 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 steps: S1: Preparation of phenylboronic acid-based sodium alginate derivatives It is prepared by reacting 3-aminophenyl boric acid hydrochloride, sodium alginate and cyclohexyl isonitrile as raw materials; 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.

[0005] Preferably, the preparation method of the phenylboronic acid sodium alginate derivative comprises the following steps: 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 isocyanide to the solution after the reaction in sequence for reaction, and dialyzing and freeze-drying after the reaction to obtain a phenylboronic acid-based sodium alginate derivative.

[0006] Preferably, the mass volume ratio of sodium alginate, 3-aminophenylborate hydrochloride, formaldehyde and cyclohexyl isocyanide is 100 g: 4-8 g: 1-5 mL: 1-10 mL.

[0007] Preferably, the temperature of the Schiff base reaction in S11 is 20-30° C. and the time is 2-4 h.

[0008] Preferably, the reaction temperature in S12 is 20-30° C., and the reaction time in the dark is 12-24 h.

[0009] Preferably, the mass ratio of soy protein isolate to purple sweet potato diacylated anthocyanidins in S2 is 15-25:1.

[0010] Preferably, the mass ratio of the phenylboronic acid-based sodium alginate derivative to the soy protein isolate is 1:0.8-1.2.

[0011] The invention provides a multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion prepared by the method.

[0012] The present invention provides an application of the multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion in the preparation of drugs for intestinal delivery of diacylated anthocyanidins.

[0013] Beneficial technical effects of the present invention: The present invention designs a hierarchical polysaccharide / protein / polyphenol ternary complex, introduces a glucose-responsive phenylboronic acid structure in the molecular design, and can adjust the interface microstructure; the emulsion of the present invention enhances the strength of the interface particle membrane and can maintain its structural integrity in the gastric environment; the targeted delivery of PSPAs in the emulsion of the present invention can reach the intestine intact, has a good inhibitory effect on α-glucosidase (α-G), and improves the bioavailability of PSPAs. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Appearance photos and particle size distribution diagrams of different substances proposed in the present invention; wherein 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; Figure 2The test diagram of the emulsion proposed in the present invention; wherein (a) is the stability characteristic of the emulsion, (b) is the apparent viscosity of the emulsion, (c) is the strain scanning measurement of the emulsion at 1 Hz, and (d) is the angular frequency scanning measurement of the emulsion at a strain of 1%; Figure 3 The microscope images and model images of the simulated digestion of the SA-PBA@SPI-PSPAs-1 emulsion proposed in the present invention; wherein a1 is a microscope image of simulated digestion in the oral cavity, a2 is a microscope image of simulated digestion in gastric juice, a3 is a microscope image of simulated digestion in the intestine for 1 hour, a4 is a microscope image of simulated digestion in the intestine for 2 hours, b1 is a model image of simulated digestion in the original state, b2 is a model image of simulated digestion in the oral cavity, b3 is a model image of simulated digestion in the stomach, b4 is a model image of simulated digestion in the intestine for 1 hour, and b5 is a model image of simulated digestion in the intestine for 2 hours; Figure 4 The inhibition rates of different substances proposed in the present invention on α-glucosidase; wherein (a) is acarbose, (b) is an aqueous solution of purple sweet potato diacylated anthocyanidins, and (c) is SA-PBA@SPI-PSPAs-1 emulsion. DETAILED DESCRIPTION

[0015] The present invention will be further explained below in conjunction with specific embodiments.

[0016] Purple sweet potato diacylated anthocyanins were purchased from Chengdu Caoyuankang Biotechnology Co., Ltd. Sodium alginate (SA, Cp, viscosity (200 ± 20) mPa-s); cyclohexyl isonitrile, 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), porcine mucosal artificial saliva and pepsin were provided by Shanghai Yuanye Biotechnology Co., Ltd.; porcine bile extract and porcine lipase were purchased from Hefei Bomei Biotechnology Co., Ltd.

[0017] 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 BioIndustries); 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 (Thermo Fisher Scientific, USA); α-glucosidase inhibitor (α-G), acarbose, and sodium carbonate (Na2CO3) were all from Shanghai Yuanye Biotechnology Co., Ltd.

[0018] All reagents used in this study were of analytical grade and required no additional purification; for all experimental procedures, Milliq water with a resistivity of 18.2 MΩ·cm at 25 °C was used. Example 1

[0019] First, 6.00 g of sodium alginate (SA) was weighed and dissolved in 300 ml of deionized water to prepare a 2 wt% stock solution. Then, the pH of the sodium alginate solution was adjusted to 3.6 using 1 M hydrochloric acid solution. At the same time, 0.33 g of 3-aminophenyl boric 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 stirred at room temperature for three hours to ensure that the Schiff base reaction was completely carried out. Next, the 3-APBA solution containing formaldehyde 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 isonitrile was added to the reaction mixture and reacted at room temperature in the dark for 24 hours. Finally, the reaction product was dialyzed in deionized water through a 3500Da dialysis bag for five days, and the dialysate was replaced every eight hours. The final step was freeze drying of the material to obtain a purified phenylboronic acid alginate derivative, designated as SA-PBA-1, with a yield of 4.45 g.

[0020] 2 mg / ml SPI solution was weighed and dissolved in 0.01 mol / L phosphate buffer (pH 6.9), stirred at room temperature for two hours using magnetic stirring, and then stored at 4°C overnight to ensure complete hydration of the protein. Next, the pH of the SPI solution was adjusted to 9.0 using 0.5 M NaOH, and the protein was degraded by heating at 120°C for 20 minutes. After degradation, the solution was cooled to room temperature in an ice bath, and the pH was adjusted to 7.0 using 0.1 M HCl, and finally refrigerated. The next step was to dissolve PSPAs in 2 mg / ml SPI solution at room temperature, control the mass ratio of SPI to PSPAs to 20:1, gently stir and keep for 24 hours, and the product was recorded as SPI-PSPAs-1.

[0021] 2 g of SA-PBA-1 and 0.2 wt% SPI-PSPAs-1 were ultrasonically mixed as the aqueous phase, and the mass ratio of SA-PBA-1 and SPI was controlled to be 1:1. Squalene was used as the oil phase and mixed into the same container at a ratio of 7:3 between the oil phase and the aqueous phase. The emulsion was obtained by shearing at 16000 rpm for 5 min using a high-speed homogenizer (T18, IKA, Germany), which was recorded as SA-PBA@SPI-PSPAs-1 emulsion. Example 2

[0022] First, 5.00 g of sodium alginate (SA) was weighed and dissolved in 300 ml of deionized water to prepare a 2 wt% stock solution. Then, the pH of the sodium alginate solution was adjusted to 3.6 using 1 M hydrochloric acid solution. At the same time, 0.33 g of 3-aminophenyl boric 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 stirred at room temperature for 2 hours to ensure that the Schiff base reaction was completely carried out. Next, the 3-APBA solution containing formaldehyde 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 isonitrile was added to the reaction mixture and reacted at room temperature in the dark for 24 hours. Finally, the reaction product was dialyzed in deionized water through a 3500Da dialysis bag for five days, and the dialysate was replaced every eight hours. The final step was freeze drying of the material to obtain a purified phenylboronic acid alginate derivative, designated as SA-PBA-2, with a yield of 4.13 g.

[0023] 2 mg / ml SPI solution was weighed and dissolved in 0.01 mol / L phosphate buffer (pH 6.9), stirred at room temperature for 1 hour using magnetic stirring, and then the solution was stored at 4°C overnight to ensure complete hydration of the protein. Next, the pH of the SPI solution was adjusted to 9.0 using 0.5 M NaOH, and the protein was degraded by heating at 120°C for 20 minutes. After degradation, the solution was cooled to room temperature in an ice bath, and the pH was adjusted to 7.0 using 0.1 M HCl, and finally refrigerated. The next step was to dissolve PSPAs in 2 mg / ml SPI solution at room temperature, control the mass ratio of SPI to PSPAs to 15:1, gently stir and keep for 24 hours, and the product was recorded as SPI-PSPAs-2.

[0024] 2 g of SA-PBA-2 and 0.2 wt% SPI-PSPAs-2 were ultrasonically mixed as the aqueous phase, and the mass ratio of SA-PBA-2 to SPI was controlled to be 1:0.8. Squalene was used as the oil phase and mixed into the same container at a ratio of 7:3 between the oil phase and the aqueous phase. The emulsion was obtained by shearing at 16000 rpm for 5 min using a high-speed homogenizer (T18, IKA, Germany), which was recorded as SA-PBA@SPI-PSPAs-2 emulsion. Example 3

[0025] First, 6.00 g of sodium alginate (SA) was weighed and dissolved in 300 ml of deionized water to prepare a 2 wt% stock solution. Then, the pH of the sodium alginate solution was adjusted to 3.6 using 1 M hydrochloric acid solution. At the same time, 0.33 g of 3-aminophenyl boronate 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 stirred at room temperature for three hours to ensure that the Schiff base reaction was completely carried out. Next, the 3-APBA solution containing formaldehyde was added to the sodium alginate stock solution with a pH value of 3.6 and stirred vigorously for half an hour. Then, 0.20 ml of cyclohexyl isonitrile was added to the reaction mixture and reacted at room temperature in the dark for 12 hours. Finally, the reaction product was dialyzed in deionized water through a 3500Da dialysis bag for five days, and the dialysate was replaced every eight hours. The final step was freeze drying of the material to obtain a purified phenylboronic acid alginate derivative, designated as SA-PBA-3, with a yield of 3.51 g.

[0026] 2 mg / ml SPI solution was weighed and dissolved in 0.01 mol / L phosphate buffer (pH 6.9), stirred at room temperature for two hours using magnetic stirring, and then the solution was stored at 4°C overnight to ensure that the protein was fully hydrated. Next, the pH of the SPI solution was adjusted to 9.0 using 0.5 M NaOH, and the protein was degraded by heating at 120°C for 20 minutes. After degradation, the solution was cooled to room temperature in an ice bath, and the pH was adjusted to 7.0 using 0.1 M HCl, and finally refrigerated. The next step was to dissolve PSPAs in 2 mg / ml SPI solution at room temperature, control the mass ratio of SPI to PSPAs to 25:1, gently stir and keep for 24 hours, and the product was recorded as SPI-PSPAs-3.

[0027] 2 g of SA-PBA-3 and 0.2 wt% SPI-PSPAs-3 were ultrasonically mixed as the aqueous phase, and the mass ratio of SA-PBA-3 and SPI was controlled to be 1:1.2. Squalene was used as the oil phase and mixed into the same container at a ratio of 7:3 between the oil phase and the aqueous phase. The emulsion was obtained by shearing at 16000 rpm for 5 min using a high-speed homogenizer (T18, IKA, Germany), which was recorded as SA-PBA@SPI-PSPAs-3 emulsion. Comparative Example 1

[0028] 0.2 wt% SA-PBA-1 as the water phase and squalene as the oil phase were mixed in the same container at a ratio of 7:3 between the oil phase and the water phase, and an emulsion was obtained by shearing at 16000 rpm for 5 min using a high-speed homogenizer (T18, IKA, Germany), which was recorded as SA-PBA emulsion. Comparative Example 2

[0029] Weigh and dissolve 2 mg / ml SPI powder in 0.01 mol / L phosphate buffer (pH 6.9), stir at room temperature for two hours using magnetic stirring, and then store the solution at 4°C overnight to ensure complete hydration of the protein. Next, adjust the pH 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, the solution was cooled to room temperature in an ice bath, and the pH was adjusted to 7.0 using 0.1 M HCl, and finally stored in a refrigerator, recorded as SPI-1 solution.

[0030] 2 g of SA-PBA-1 and 0.2 wt% SPI-1 solution were ultrasonically mixed as the aqueous phase, and the mass ratio of SA-PBA-1 and SPI was controlled to be 1:1. Squalene was used as the oil phase and mixed into the same container at a ratio of 7:3 between the oil phase and the aqueous phase. The emulsion was obtained by shearing at 16000 rpm for 5 min using a high-speed homogenizer (T18, IKA, Germany), which was recorded as SA-PBA@SPI emulsion.

[0031] Figure 1 The following are the appearance photos, optical microscope images (20 μm) and 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 is milky white and shows rheological reversal, while the emulsion with PSPAs is purple-red and turns into a gel when reversed. By observing the emulsion under 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 of about 45 μm; after adding SA-PBA@SPI, the particle size of the emulsion dropped to about 18 μm. The emulsion with SA-PBA@SPI-PSPAs showed the smallest particle size of about 15 μm. These results show that SA-PBA, SA-PBA@SPI and SA-PBA@SPI-PSPAs all have excellent amphiphilic affinity.

[0032] The TSI value is an accurate indicator of emulsion stability, and a higher TSI value corresponds to weaker stability. Figure 2Part (a) shows the changes in TSI values ​​of SA-PBA@SPI-stabilized emulsions with and without the addition of PSPAs over a 6-hour period. The results show that the TSI values ​​of all emulsions increased over time, reflecting a gradual decrease in stability. Specifically, the TSI value of the SA-PBA emulsion started at about 10, decreased to about 6 after the addition of SPI, and further decreased to about 2 after the addition of 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, which formed a cross-linked three-dimensional network with SPI@PSPAs, and jointly stabilized the Pickering emulsion.

[0033] The rheological properties of emulsions are crucial to assess their stability, and interfacial rheology is affected by interfacial adsorption and molecular interactions. Figure 2 Part (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.

[0034] 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) of Figure 1 shows a model diagram of the simulated digestion of the SA-PBA@SPI-PSPAs-1 emulsion. Initially, after 5 min of digestion in simulated oral fluid, the morphology of the emulsion droplets was similar to the original droplets, and the droplet size did not change significantly. This is because the simulation of the oral stage lasted only 5 min, which was too short to cause obvious emulsification decomposition. Next, after 1 h of digestion in simulated gastric fluid, the morphology of the droplets was still similar to 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 and the pH value of simulated gastric fluid being 2.5. At this acidic pH value, below the pKa, SA-PBA tends to form acidic gels, which enhances the stability of the emulsion. Finally, after 1 h of digestion in simulated intestinal fluid, emulsification decomposition occurred significantly, and after 2 h, the emulsion was completely decomposed. This is because the neutral pH value of the intestinal fluid (approximately pH 7.0), which is close to the pKa value of sodium alginate, leads to complete emulsification decomposition and promotes the release of PSPAs in the intestine.

[0035] We compared the inhibitory effects of PSPAs aqueous solution (solution of PSPAs dissolved in water) and SA-PBA@SPI-PSPAs-1 emulsion on α-glucosidase (α-G). Figure 4 As shown in the figure, the inhibitor concentration was positively correlated with the inhibitory effect on α-G and exhibited a dose-dependency. Specifically, the IC50 value of the PSPAs emulsion was lower than that of the PSPAs aqueous solution and close to that 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 by non-competitive inhibition. They do not bind directly to the active site of the enzyme, but interact with other regions or auxiliary structures of the enzyme, causing conformational changes or changing the stability of the enzyme, thereby reducing its activity. In contrast, some PSPAs in the PSPAs emulsion bind to SPI to form quinone compounds, which can directly interact with the active site of α-G to form an enzyme-inhibitor complex, directly preventing the binding of the enzyme to the substrate, or further changing the conformation of the enzyme, thereby reducing its catalytic efficiency.

[0036] Although the embodiments of the present application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations may be made to the 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 all shall be included in the scope of protection of the present application.

Claims

1. A method for preparing a multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion, characterized in that: The steps are as follows: S1: Preparation of phenylboronic acid-based sodium alginate derivatives It is prepared by reacting 3-aminophenyl boric acid hydrochloride, sodium alginate and cyclohexyl isonitrile as raw materials; 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 responsive Pickering emulsion according to claim 1, characterized in that: The preparation method of phenylboronic acid sodium alginate derivatives is as follows: 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 isocyanide to the solution after the reaction in sequence for reaction, and dialyzing and freeze-drying after the reaction to obtain a phenylboronic acid-based sodium alginate derivative.

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

4. The method for preparing the multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion according to claim 2, characterized in that: The temperature of the Schiff base reaction in S11 is 20-30°C and the time is 2-4h.

5. The method for preparing the multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion according to claim 2, characterized in that: The reaction temperature in S12 is 20-30°C, and the reaction time is 12-24 hours in the dark.

6. The method for preparing the multiple non-covalent bond enhanced pH / glucose responsive 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.

7. The method for preparing the multiple non-covalent bond enhanced pH / glucose responsive Pickering emulsion according to claim 1, characterized in that: The mass ratio of the phenylboronic acid-based sodium alginate derivative to the soy protein isolate is 1:0.8-1.

2.

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

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

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