Intestinal targeting probiotic emulsion gel capsule and preparation method thereof

Abstract

The invention discloses an intestinal targeting probiotic emulsion gel capsule and a preparation method thereof. The preparation method comprises the following steps: firstly, preparing an acidic water phase containing probiotics and cationic polysaccharide, and preparing an oil phase containing a hydrophobic solid particle emulsifier and edible oil; the oil phase and the water phase are emulsified at a high speed, and stable emulsion gel is formed on an oil-water interface by utilizing an electrostatic crosslinking effect between the cationic polysaccharide and solid particles; further, edible colloid is used as a shell, and the emulsion gel inner core is packaged through a micro-fluidic technology to prepare the emulsion gel capsule. The emulsion gel disclosed by the invention can effectively resist a gastric acid environment, protect the activity of probiotics and realize targeted release in intestinal tracts by digesting an oil phase through lipase. The capsule is completely made of safe materials approved by FDA, has good stability, machinability and biocompatibility, remarkably improves the oral delivery efficiency of probiotics, and is suitable for the field of functional food and pharmaceutical preparations.

Description

Technical Field

[0001] This invention relates to the field of probiotic emulsion gels, specifically to an intestinal-targeting probiotic emulsion gel capsule and its preparation method. Background Technology

[0002] Probiotics are live microorganisms that offer numerous health benefits, primarily in regulating the balance of gut microbiota, enhancing immunity, and promoting nutrient absorption. However, because probiotics are highly susceptible to the acidic environment of the stomach, they lose their activity before reaching the intestines, which limits their application in functional foods and pharmaceutical preparations.

[0003] To overcome the aforementioned problems, microencapsulation technology has been extensively studied and applied to the protection of probiotics in highly acidic environments. Common microencapsulation methods in previous studies include spray drying, electrospray drying, freeze drying, and emulsification. While these methods have all made some progress in protecting probiotics, they still have significant limitations. Existing methods suffer from insufficient probiotic protection, food safety risks, difficulty in achieving controlled release, and poor processing performance.

[0004] In recent years, Pickering emulsions have shown promising prospects in the delivery field due to their advantages such as high stability and low toxicity, achieved by using solid particles as emulsifiers. The physical isolation structure formed in oil-in-water emulsion systems effectively isolates active substances from the external environment, protecting probiotics from acidic environments through a continuous oil phase. Despite the potential of Pickering emulsions in probiotic delivery, technical challenges remain in their practical application. Oil-in-water Pickering emulsions suffer from issues such as droplet aggregation, insufficient structural strength, processing difficulties, and challenges in oral administration, making it difficult to meet the dual requirements of long-term protection and targeted release in probiotic delivery.

[0005] Given the aforementioned technological challenges, developing an emulsion gel that utilizes fully FDA-approved materials and possesses both good stability and processability is crucial for achieving targeted intestinal delivery of probiotics. Furthermore, developing a formulation method capable of encapsulating the aforementioned probiotic emulsion gel is also urgently needed to achieve safe and convenient oral administration. Summary of the Invention

[0006] To achieve targeted delivery of probiotics into the intestine, this invention proposes an intestinal-targeted probiotic emulsion gel capsule and its preparation method. This invention solves the core problems in existing technologies, such as the low survival rate of probiotics in the acidic gastric environment and the inability to precisely target and release them, and also provides a promising solution for the targeted intestinal delivery of sensitive substances.

[0007] This invention first provides a method for preparing a probiotic gut-targeted emulsion gel capsule, comprising the following steps: S1: Cationic polysaccharides and probiotics are dissolved in an acidic aqueous solution to form an aqueous phase; hydrophobic solid particulate emulsifiers are dispersed in edible oil to form an oil phase; S2: The aqueous phase and oil phase obtained in step S1 are mixed and then emulsified at high speed to obtain the internal phase; S3: Dissolve the edible colloid in deionized water, heat and stir to prepare a shell solution as the external phase; S4: The inner phase and the outer phase are introduced into a microfluidic device with coaxial channels. The inner phase is injected into the inner channel of the microfluidic device, and the outer phase is injected into the outer channel. At the outlet, the outer phase shears the inner phase to form a core-shell structure capsule, which drips into the collection pool and solidifies to form a robust core-shell capsule.

[0008] As a preferred embodiment of the present invention, the cationic polysaccharide is one or more of chitosan, chitosan derivatives, and cationic cellulose, and the concentration range of the cationic polysaccharide in the aqueous phase is 5-25 mg / mL; the concentration of the probiotics in the aqueous phase is 5-15 mg / mL.

[0009] In a preferred embodiment of the present invention, the aqueous phase is an acidic aqueous solution containing an acid that can dissolve cationic polysaccharides and impart a positive charge. Preferably, the acid is an edible organic acid, including but not limited to one or more of citric acid, acetic acid, and lactic acid, with the acidic substance comprising 1-5 wt% by mass.

[0010] As a preferred embodiment of the present invention, the oil phase used in step S1 is a monounsaturated fatty acid type edible oil that is more easily degraded and digested, including but not limited to one or more of olive oil, tea seed oil, rapeseed oil, almond oil and avocado oil.

[0011] As a preferred embodiment of the present invention, the hydrophobic solid particle emulsifier mentioned in step S1 is a food-grade solid particle such as SiO2 or starch particles, and its concentration in the oil phase is 10-25 mg / mL.

[0012] As a preferred embodiment of the present invention, in step S2, the aqueous phase and the oil phase are mixed and emulsified at high speed, and a Pickering emulsion gel is formed by electrostatic crosslinking of cationic polysaccharides and solid nanoparticles; the volume ratio of the oil phase and the aqueous phase is (35-45):(65-55).

[0013] As a preferred embodiment of the present invention, the emulsification method described in step S2 includes, but is not limited to, high-speed shearing, vortex oscillation, and high-speed homogenization. Preferably, the emulsification time is 1-5 minutes.

[0014] As a preferred embodiment of the present invention, the shell solution in step S3 can be other edible colloids such as gelatin and sodium alginate, and the heating and stirring dissolution temperature is maintained at 60-70 ℃.

[0015] As a preferred embodiment of the present invention, when selecting gelatin as the edible colloid in step S3, its concentration is 20-30 wt%, and glycerol with a concentration of 5-10 wt% is added to the external phase as a plasticizer, and low-temperature curing is carried out in the collection tank; preferably, if an ice bath, oil bath or water bath is used in the collection tank, its preferred temperature is 0-4 ℃; more preferably, an ice-water mixture is pre-set in the collection tank as the collection liquid.

[0016] When sodium alginate is selected as the edible colloid, the concentration of sodium alginate in the external phase is 1-5 wt%, and a calcium chloride solution with a calcium ion concentration of 1-5 wt% is provided in the collection tank.

[0017] As a preferred embodiment of the present invention, the microfluidic device shown in step S4 employs a coaxial design, where the two phases are sheared at the device outlet to form a core-shell capsule with an emulsion gel as the core. The capsule is dropped into a collection tank to solidify the surface layer, and then the capsule is placed in air to dry, obtaining a robust core-shell capsule.

[0018] As a preferred embodiment of the present invention, the internal phase flow rate in step S4 is 0.3-0.8 mL / min, and the external phase flow rate is 0.5-1.5 mL / min. The inner tube diameter at the outlet of the microfluidic device is 500-800 μm, and the outer tube diameter is 1.5-2.0 cm.

[0019] The present invention also provides probiotic emulsion gel and probiotic emulsion gel capsules prepared by the aforementioned method.

[0020] This invention further provides the application of the prepared probiotic emulsion gel or probiotic emulsion gel capsule in the preparation of oral formulations, wherein the oral formulation can be a food, food additive, or drug; typically, but not limited to, it can be a food or food additive that regulates the balance of intestinal flora, or a drug for treating intestinal diseases, such as drugs for treating ulcerative colitis or constipation. The probiotic emulsion gel capsules of this invention exert the effects of probiotics on regulating the balance of intestinal flora and treating ulcerative colitis or constipation by releasing active probiotics in a targeted manner in the intestine.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows: 1) The emulsion gel capsules obtained by the present invention can effectively protect probiotics from the influence of gastric acid environment and can achieve targeted release of active probiotics in the intestine.

[0022] 2) The probiotic-loaded emulsion gel capsules proposed in this invention exhibit good stability under different pH values, temperatures and time conditions, which improves the survival rate of probiotics in the gastric acid environment.

[0023] 3) The release of probiotics in the emulsion gel capsule proposed in this invention is dominated by intestinal lipase. When the emulsion gel capsule enters the intestine, the continuous oil phase can be digested by lipase to release probiotics with good activity.

[0024] 4) The emulsion gel capsules prepared by this invention exhibit good stability and processability, enabling the preparation of core-shell capsules through microfluidic technology, thus facilitating oral administration.

[0025] 5) Compared to other microencapsulation technologies, the materials used in this solution are all FDA-approved, with no organic solvent residues and extremely low safety risks. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the probiotic emulsion gel provided by the present invention; Figure 2 This is a schematic diagram of the microfluidic preparation of probiotic emulsion gel core-shell capsules according to the present invention.

[0027] Figure 3 This is a staining diagram of the live and dead bacteria of the probiotics of this invention in a simulated stomach and intestinal environment.

[0028] Figure 4 This is a graph showing the stability test of the emulsion gel of the present invention at different temperatures.

[0029] Figure 5 This is a graph showing the stability test of the emulsion gel of the present invention at different pH values.

[0030] Figure 6 This is a graph showing the long-term stability test of the probiotic emulsion gel core-shell capsule of the present invention.

[0031] Figure 7 This is a graph showing the dissolution changes of the outer shell of the probiotic emulsion gel core-shell capsule of the present invention in an aqueous solution at 37 ℃. Detailed Implementation

[0032] The present invention will be further described and illustrated below with reference to specific embodiments. The embodiments described are merely examples of the content of this disclosure and do not limit the scope of the invention. The technical features of each embodiment in the present invention can be combined accordingly without mutual conflict. The raw materials involved in each embodiment of the present invention are all commercially available. Among them, the probiotics are purchased from Biostime, a subsidiary of the Jianhe Group, and the probiotic concentration is 1×10⁻⁶. 10 CFU / g.

[0033] like Figure 2 As shown, the microfluidic devices used in each embodiment include an inner tube and an outer tube arranged coaxially. Both the inner tube and the outer tube have a tapered diameter reduction design at the outlet to achieve the preparation of core-shell capsules. The outlet diameter of the inner tube is 500-800 μm, and the outlet diameter of the outer tube is 1.5-2.0 cm.

[0034] Example 1: Gelatin-based chitosan (citric acid)-silica (olive oil) encapsulation system S1: Chitosan and probiotics were dissolved in a 2 wt% citric acid aqueous solution to obtain an aqueous phase, in which the concentration of chitosan was 15 mg / mL and the concentration of probiotics was 10 mg / mL. The oil phase consisted of silica nanoparticles dissolved in olive oil, with a silica nanoparticle concentration of 20 mg / mL.

[0035] S2: The two phases obtained in step S1 are mixed at a water-to-oil volume ratio of 6:4, and emulsified at high speed using a vortex mixer for 3 minutes. The resulting product is taken as the inner phase, such as... Figure 1 As shown.

[0036] S3: Dissolve gelatin and glycerin in deionized water, wherein the percentage content of gelatin is 26 wt% and the percentage content of glycerin is 8 wt%, and stir and mix at 65°C to obtain the external phase.

[0037] S4: As Figure 2 As shown, the inner and outer phases were introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.5 mL / min:0.8 mL / min. The outer phase sheared the inner phase at the channel opening to obtain core-shell capsules. The prepared core-shell capsules were collected in a cold container cooled by an ice-oil bath (a certain amount of ice water was added to the container as a coolant to gelatinize the gelatin shell). After the gelatin shell gelled at low temperature, the capsules were dried in air to form a solid capsule.

[0038] Probiotics were stained with Calcein AM / PI using live cells (green) and dead cells (red). Free probiotics and probiotic emulsion gels were incubated for 2 hours before oral administration under simulated gastric (containing pepsin, pH=2) and simulated intestinal (containing pepsin and lipase, pH=7) conditions. Results are as follows: Figure 3 As shown, most probiotics remained active and exhibited green fluorescence before oral administration. However, after 2 hours of incubation in a simulated gastric / intestinal environment, most free probiotics showed impaired activity and exhibited red fluorescence, indicating that the free probiotics were eroded by gastric acid and could not smoothly enter the intestine for release. When probiotics were encapsulated in an emulsion gel, most of the probiotics exhibited green fluorescence and remained active after 2 hours of incubation in a simulated gastric environment. Furthermore, in a simulated intestinal environment, as lipases consumed the oil phase, the probiotics remained green fluorescent after release, maintaining their activity. The method of this invention, which encapsulates probiotics in an emulsion gel, satisfies the dual requirements of long-term protection and targeted delivery of probiotics.

[0039] The stability of the emulsion gel was tested at different temperatures, and the results are as follows: Figure 4As shown, the gel remains stable within the range of 4-50 °C. Although the gel is damaged at -20 °C, it can be restored to its gel state by simple vortex oscillation. The emulsion gel of this invention can remain stable at different temperatures.

[0040] The stability of the emulsion gel at different pH values ​​was tested, and the results are as follows: Figure 5 As shown, when the emulsion gel is immersed in water, the emulsion gel of the present invention exhibits good stability over a wide pH range from 2 to 12.

[0041] The probiotic emulsion gel core-shell capsules exhibit good long-term storage stability, as shown in the following results. Figure 6 As shown, the core-shell capsule of the present invention still exhibits good stability after 30 days of storage.

[0042] like Figure 7 As shown, the outer shell of the probiotic emulsion gel capsule can be dissolved in an aqueous solution at 37 °C. After 35 minutes, the outer shell is almost completely dissolved, but the probiotic emulsion gel core remains undissolved. The probiotic emulsion gel capsule of the present invention can be used to make oral preparations.

[0043] Example 2: Chitosan (citric acid)-silica (olive oil) encapsulation system based on sodium alginate S1: Chitosan and probiotics were dissolved in a 2 wt% citric acid aqueous solution to obtain an aqueous phase, in which the concentration of chitosan was 15 mg / mL and the concentration of probiotics was 10 mg / mL. The oil phase consisted of silica nanoparticles dissolved in olive oil, with a silica nanoparticle concentration of 20 mg / mL.

[0044] S2: The two phases obtained in step S1 are mixed with water and oil at a volume ratio of 6:4, and emulsified at high speed for 3 minutes using a vortex oscillator. The resulting product is taken as the inner phase.

[0045] S3: Dissolve sodium alginate in deionized water to prepare a 1.6 wt% sodium alginate solution as the external phase, and simultaneously prepare a 5 wt% calcium chloride solution as the collecting liquid.

[0046] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.5 mL / min:1.5 mL / min, respectively. The outer phase shears the inner phase at the channel opening to form core-shell capsules. The prepared core-shell capsules are collected in a container containing a collection solution. After cross-linking and solidification by calcium ions in the coagulation solution, probiotic emulsion gel capsules are prepared. Subsequent filtration and collection complete the bottling of the probiotic emulsion gel capsules.

[0047] Example 3: Chitosan (lactic acid)-silica (rapeseed oil) encapsulation system based on sodium alginate S1: Chitosan and probiotics were dissolved in an aqueous lactic acid solution to obtain an aqueous phase. In the aqueous phase, the concentration of chitosan was 10 mg / mL, the concentration of probiotics was 6 mg / mL, and the content of lactic acid was 10 mg / mL. The oil phase consisted of silica nanoparticles dissolved in rapeseed oil with a concentration of 10 mg / mL.

[0048] S2: The two phases obtained in step S1 are mixed at a water-oil volume ratio of 1:1 and emulsified at 8000 rpm for 5 minutes using a high-speed shear machine to obtain the inner phase.

[0049] S3: Dissolve 1.4 wt% sodium alginate in deionized water as the external phase, and simultaneously prepare a 3.5 wt% calcium chloride solution as the collecting liquid.

[0050] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.4 mL / min:0.8 mL / min, respectively. The outer phase shears against the inner phase at the channel opening to form core-shell capsules. The prepared core-shell capsules are collected in a container containing a collection solution. After cross-linking and solidification by calcium ions in the coagulation solution, probiotic emulsion gel capsules are prepared. Subsequent filtration and collection complete the bottling of the probiotic emulsion gel capsules.

[0051] Example 4: Gelatin-based chitosan (lactic acid)-silica (olive oil) encapsulation system S1: Chitosan and probiotics were dissolved in a 2.5 wt% lactic acid aqueous solution to obtain an aqueous phase. In the aqueous phase, the concentration of chitosan was 22 mg / mL and the concentration of probiotics was 8 mg / mL. The oil phase consisted of silica nanoparticles dissolved in olive oil with a concentration of 25 mg / mL.

[0052] S2: The two phases obtained in step S1 are mixed with water and oil at a volume ratio of 1:1, and emulsified at 8000 rpm for 5 minutes using a high-speed shear machine to obtain the inner phase.

[0053] S3: Dissolve gelatin and glycerin in deionized water, wherein the percentage content of gelatin is 26 wt% and the percentage content of glycerin is 8 wt%, and stir and mix at 70°C to obtain the external phase.

[0054] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.5:0.8 mL / min. The outer phase shears the inner phase at the channel opening to obtain core-shell capsules. The prepared core-shell capsules are collected in a cold container (pre-filled with ice water) cooled by an ice-oil bath. After the gelatin shell gelles at low temperature, the capsules are dried in air to form robust solid capsules. Example 5: Gelatin-based cationic cellulose (lactic acid)-silica (olive oil) encapsulation system S1: Cationic cellulose and probiotics were dissolved in a 2 wt% lactic acid aqueous solution to obtain an aqueous phase. In the aqueous phase, the cationic cellulose concentration was 15 mg / mL and the probiotic concentration was 10 mg / mL. The oil phase consisted of silica nanoparticles dissolved in olive oil with a silica nanoparticle concentration of 20 mg / mL.

[0055] S2: The two phases obtained in step S1 are mixed with water and oil at a volume ratio of 1:1, and emulsified at 8000 rpm for 3 minutes using a high-speed shear machine to obtain the inner phase.

[0056] S3: Dissolve gelatin and glycerin in deionized water, wherein the percentage content of gelatin is 26 wt% and the percentage of glycerin is 8 wt%, and stir and mix at 65°C to obtain the external phase.

[0057] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.3 mL / min:0.5 mL / min, respectively. The outer phase shears the inner phase at the channel opening to obtain core-shell capsules. The prepared core-shell capsules are collected in a cold container (pre-filled with ice water) cooled by an ice-oil bath. After the gelatin shell gelles at low temperature, the capsules are dried in air to form robust solid capsules. Example 6: Gelatin-based cationic cellulose (acetic acid)-starch granule (rapeseed oil) encapsulation system S1: Cationic cellulose and probiotics were dissolved in a 3 wt% aqueous acetic acid solution to obtain an aqueous phase, in which the cationic cellulose concentration was 25 mg / mL and the probiotic concentration was 10 mg / mL. The oil phase consisted of octenyl succinate starch nanoparticles dissolved in rapeseed oil, with an octenyl succinate starch nanoparticle concentration of 25 mg / mL.

[0058] S2: Mix the two phases obtained in step S1 with a water-oil volume ratio of 6:4, and emulsify them at high speed for 3 minutes using a vortex oscillator to obtain the inner phase.

[0059] S3: Dissolve gelatin and glycerin in deionized water, wherein the percentage content of gelatin is 25 wt% and the percentage of glycerin is 8 wt%, and stir and mix at 65°C.

[0060] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.8 mL / min:1.5 mL / min, respectively. The outer phase shears the inner phase at the channel opening to obtain core-shell capsules. The prepared core-shell capsules are collected in a cold container (pre-filled with ice water) cooled by an ice-oil bath. After the gelatin shell gelles at low temperature, the capsules are dried in air to form a robust solid capsule.

[0061] Example 7: Cationic cellulose (acetic acid)-starch granule (rapeseed oil) encapsulation system based on sodium alginate S1: Cationic cellulose and probiotics were dissolved in a 2.5 wt% acetic acid aqueous solution to obtain an aqueous phase. In the aqueous phase, the cationic cellulose concentration was 20 mg / mL and the probiotic concentration was 8 mg / mL. The oil phase consisted of octenyl succinate starch nanoparticles dissolved in rapeseed oil, with an octenyl succinate starch nanoparticle concentration of 20 mg / mL.

[0062] S2: The two phases obtained in step S1 are mixed with water and oil at a volume ratio of 1:1, and emulsified at 8000 rpm for 3 minutes using a high-speed shear machine to obtain the inner phase.

[0063] S3: Dissolve 1.2 wt% sodium alginate in deionized water as the external phase, and simultaneously prepare a 2.5 wt% calcium chloride solution as the collecting liquid.

[0064] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.5:1.25 mL / min. The outer phase shears against the inner phase at the channel opening to form core-shell capsules. The prepared core-shell capsules are collected in a container containing a collection solution. After cross-linking and solidification by calcium ions in the coagulation solution, probiotic emulsion gel capsules are prepared. Subsequent filtration and collection complete the bottling of the probiotic emulsion gel capsules.

[0065] Example 8: Chitosan hydrochloride (lactic acid)-starch nanoparticle (rapeseed oil) encapsulation system based on sodium alginate S1: Chitosan hydrochloride and probiotics were dissolved in a 2 wt% lactic acid aqueous solution to obtain an aqueous phase. In the aqueous phase, the concentration of chitosan hydrochloride was 25 mg / mL and the concentration of probiotics was 10 mg / mL. The oil phase consisted of octenyl succinate starch nanoparticles dissolved in rapeseed oil with a concentration of 35 mg / mL.

[0066] S2: The two phases obtained in step S1 are mixed with water and oil at a volume ratio of 6:4, and emulsified at 10,000 rpm for 5 minutes using a high-speed shear homogenizer to obtain the inner phase.

[0067] S3: Dissolve 2 wt% sodium alginate in deionized water as the external phase, and simultaneously prepare a 3 wt% calcium chloride solution as the collecting liquid.

[0068] S4: The inner and outer phases are introduced into a microfluidic device with a coaxial channel at a flow rate ratio of 0.3 mL / min:0.6 mL / min, respectively. The outer phase shears the inner phase at the channel opening to form core-shell capsules. The prepared core-shell capsules are collected in a container containing a collection solution. After cross-linking and solidification by calcium ions in the coagulation solution, probiotic emulsion gel capsules are prepared. Subsequent filtration and collection complete the bottling of the probiotic emulsion gel capsules.

[0069] The above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to the embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the present invention or equivalent substitutions can be made to some technical features; without departing from the spirit and scope of the inventive concept, all changes and advantages that those skilled in the art can conceive of should be covered within the scope of the technical solutions claimed in the present invention.

Claims

1. A method for preparing an intestinal-targeted probiotic emulsion gel capsule, characterized in that, Includes the following steps: S1: Cationic polysaccharides and probiotics are dissolved in an acidic aqueous solution to form an aqueous phase; hydrophobic solid particulate emulsifiers are dispersed in edible oil to form an oil phase; S2: The aqueous phase and oil phase obtained in step S1 are mixed and then emulsified at high speed to obtain the internal phase; S3: Dissolve the edible colloid in deionized water, heat and stir to prepare a shell solution as the external phase; S4: The inner phase and the outer phase are introduced into a microfluidic device with coaxial channels. The inner phase is injected into the inner channel of the microfluidic device, and the outer phase is injected into the outer channel. At the outlet, the outer phase shears the inner phase to form a core-shell structure capsule, which drips into the collection pool and solidifies to form a robust core-shell capsule.

2. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The cationic polysaccharide is one or more of chitosan, chitosan derivatives, and cationic cellulose, and the concentration range of the cationic polysaccharide in the aqueous phase is 5-25 mg / mL; the concentration of the probiotics in the aqueous phase is 5-15 mg / mL.

3. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The aqueous phase is an acidic aqueous solution containing acidic substances, which are one or more of citric acid, acetic acid, lactic acid, and malic acid, with a mass percentage of 1-5 wt%.

4. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The hydrophobic solid particulate emulsifier is one or more of SiO2 and starch granules, and its concentration in the oil phase is 10-25 mg / mL.

5. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The oil in the oil phase is an easily degradable and digestible monounsaturated fatty acid type edible oil, including one or more of olive oil, tea seed oil, rapeseed oil, almond oil, and avocado oil.

6. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The aqueous and oil phases were mixed and emulsified at high speed to form Pickering emulsion gel through electrostatic cross-linking of cationic polysaccharides with solid nanoparticles; the volume ratio of oil phase to aqueous phase was (35-45):(65-55).

7. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The edible colloid is one or more of gelatin and sodium alginate; the heating and stirring dissolution temperature is maintained at 60-70 ℃; when gelatin is selected as the edible colloid, its concentration is 20-30 wt%, and glycerol with a concentration of 5-10 wt% is added to the external phase as a plasticizer; an ice-water mixture is set in the collection tank for low-temperature curing. When sodium alginate is selected as the edible colloid, the concentration of sodium alginate in the external phase is 1-5 wt%, and a calcium chloride solution with a calcium ion concentration of 1-5 wt% is provided in the collection tank.

8. The method for preparing emulsion gel capsules according to claim 1, characterized in that: The internal phase flow rate is 0.3-0.8 mL / min, and the external phase flow rate is 0.5-1.5 mL / min; the inner tube diameter at the outlet of the microfluidic device is 500-800 μm, and the outer tube diameter is 1.5-2.0 cm.

9. A gut-targeting probiotic emulsion gel capsule, characterized in that, It is prepared by the method described in any one of claims 1-9.

10. The use of the probiotic emulsion gel capsule of claim 9 in the preparation of food or food additives that regulate the balance of intestinal flora.

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