A microsphere capsule for hemostasis and repair of gastric mucosa based on Bletilla striata and its preparation method

Abstract

This invention provides a gastric mucosal surface hemostasis and repair microsphere capsule based on Bletilla striata, prepared by the following method: First, a Bletilla striata polysaccharide solution and a pectin solution are stirred and mixed to obtain a viscous mixture, which is then allowed to stand. Next, the viscous mixture is mixed evenly with lecithin in an organic solvent to obtain a Bletilla striata pectin phospholipid complex. The Bletilla striata pectin phospholipid complex is added to a self-microemulsion drug delivery system to obtain a transparent liquid. The transparent liquid is then added dropwise under an electrostatic field to an aqueous solution containing carboxymethyl chitosan and acetic acid, followed by the addition of an aqueous solution of sodium citrate, to obtain gel microspheres with a shell structure. After standing, microspheres with an uneven surface are obtained. The uneven surface microspheres are then solidified and freeze-dried to obtain the gastric mucosal surface hemostasis and repair microsphere capsule based on Bletilla striata. The microsphere capsules of this invention can achieve highly efficient hemostasis and repair of the gastric mucosal surface, and their ingredients are natural, safe, and have few side effects, making them suitable for the treatment of various gastric mucosal injuries and bleeding.

Description

Technical Field

[0001] This invention provides a microsphere capsule for hemostasis and repair of gastric mucosa based on Bletilla striata and its preparation method, belonging to the field of biomedical technology. Background Technology

[0002] Gastric mucosal injury and bleeding are common digestive system diseases in clinical practice. The gastric mucosa is the inner lining of the stomach. When the gastric mucosa is damaged, it can lead to serious consequences such as bleeding, severely affecting the patient's life and health. Currently, most commonly used gastric mucosal repair and hemostatic drugs are chemically synthesized. Although they have certain efficacy, there are still some problems in terms of treatment effect and side effects, and long-term use can easily lead to drug resistance. In recent years, with the development of the biomedical field, the research and development of a biomedical agent with good biocompatibility and significant efficacy for gastric mucosal surface hemostasis and repair has gradually become a research hotspot in this field.

[0003] In the prior art, the journal "Evaluation of the Gastric Ulcer Targeting Effect and Protective Effect of Evodiaein Phospholipid Complex Self-Microemulsion Drug Delivery System" (DOI: 10.7501 / j.issn.0253-2670.2024.01.018, publication date: January 2024) evaluated the gastric ulcer targeting effect of the evodiaein phospholipid complex by analyzing fluorescence imaging results and laser confocal microscopy fluorescence imaging results. The evodiaein phospholipid complex showed good protective effect against an ethanol-induced rat gastric ulcer model. This preparation mainly relieves the symptoms of gastric diseases through its anti-inflammatory, analgesic, and anti-ulcer effects, rather than exerting its therapeutic effect by protecting the gastric mucosa, promoting ulcer healing, and inhibiting Helicobacter pylori growth. Therefore, it cannot better solve the problem of gastric diseases from the root cause.

[0004] Bletilla striata, a perennial herb of the Orchidaceae family, is a traditional Chinese medicine used for hemostasis. Its polysaccharides possess excellent water absorption and swelling properties, capable of absorbing large amounts of water and swelling rapidly. It also exhibits good tissue compatibility, bioadhesion, biodegradability, and non-irritation to mucous membranes, making it widely applicable in the biomedical field. The mucilage and starch components in Bletilla striata can coat damaged gastric mucosa, forming a protective layer and reducing irritation from gastric acid and pepsin. Simultaneously, the active ingredients in Bletilla striata can promote epidermal cell proliferation and accelerate ulcer repair. However, how to use Bletilla striata as the main drug and precisely target it to the damaged gastric mucosa to achieve targeted efficacy remains an unsolved problem in this field. Summary of the Invention

[0005] To address the problems in the background art, this application specifically provides a gastric mucosal surface hemostasis and repair microsphere capsule based on Bletilla striata. This microsphere capsule utilizes the water absorption and swelling properties of Bletilla striata and uses a self-microemulsion drug delivery system as a drug carrier for targeted and localized action. At the same time, the special structure of the concave and convex microspheres on the surface of the microsphere capsule adheres to the surface of the gastric ulcer, thereby achieving the function of targeted hemostasis and repair.

[0006] The technical solution adopted to achieve the above-mentioned objectives of this invention is as follows:

[0007] A microsphere capsule for hemostasis and repair of gastric mucosa based on Bletilla striata, wherein the microsphere capsule is prepared by the following method:

[0008] (1) Mix the Bletilla striata polysaccharide solution and pectin solution in a volume ratio of 1:1 to 3:1 to obtain a viscous mixture and let it stand.

[0009] (2) The viscous mixture and lecithin were mixed evenly in an organic solvent at a mass ratio of 1:2 to 2:1, and then the organic solvent was removed to obtain the Bletilla striata pectin phospholipid complex.

[0010] (3) Add the Bletilla striata pectin phospholipid complex to the self-microemulsion drug delivery system and dissolve it completely to obtain a transparent liquid;

[0011] (4) A transparent liquid is added dropwise to an aqueous solution containing carboxymethyl chitosan and acetic acid under the action of an electrostatic field, and then an aqueous solution of sodium citrate is added. The mixture is stirred to carry out secondary cross-linking and obtains gel microspheres with a shell structure. The gel microspheres are allowed to stand at room temperature to obtain microspheres with uneven surfaces after gravity sedimentation.

[0012] (5) The surface-concave microspheres are cured under ultraviolet light and some sodium citrate in the shell is washed away in an alkaline solution. After pre-cooling, they are freeze-dried in a freeze dryer to obtain gastric mucosal surface hemostasis and repair microsphere capsules based on Bletilla striata.

[0013] Furthermore, the microsphere capsules are spherical in shape with a particle size of 8-10 μm, and are composed of an inner core layer and an outermost coating layer. The inner core layer is a complex of Bletilla striata polysaccharide-pectin-lecithin, and the outermost coating layer is a carboxymethyl chitosan coating layer with a surface uneven structure.

[0014] Furthermore, the preparation method of the Bletilla striata polysaccharide solution in step (1) is as follows:

[0015] Add Bletilla striata polysaccharide to deionized water to prepare a Bletilla striata polysaccharide solution with a mass fraction of 3-10%. Stir the solution with a magnetic stirrer at a temperature of 50℃-70℃ for 2-4 hours to completely dissolve the Bletilla striata polysaccharide in the deionized water. Then place the solution in a vacuum environment with a vacuum degree of -0.01 to -0.05 MPa to remove air bubbles, thus obtaining the Bletilla striata polysaccharide solution.

[0016] Furthermore, the extraction method of the Bletilla striata polysaccharide is as follows:

[0017] a1. Soak dried Bletilla striata stems in distilled water at a mass ratio of 1:3 to 1:10, filter with gauze to remove impurities, collect the preliminarily cleaned Bletilla striata stems and dry in an oven at 30 to 50°C for 18 to 24 hours;

[0018] a2. Soak the pre-cleaned and dried Bletilla striata stem pieces in anhydrous ethanol for 1-3 hours at a temperature of 20-30°C. Filter the mixture through gauze to remove soluble pigments. Collect the Bletilla striata stem pieces and dry them in an oven for 18-24 hours.

[0019] a3. Soak the Bletilla striata stem pieces (after removing pigments) in distilled water at a mass ratio of 1:3 to 1:10 for 0.5 to 3 hours at a temperature of 50 to 90°C. Use a magnetic stirrer to continuously stir the mixture at room temperature for about 2 hours to ensure thorough mixing. Transfer the mixture to a hot water bath and heat it to 95°C. Maintain this temperature for 1 hour. After heating, cool the mixture to room temperature.

[0020] a4. Centrifuge the mixture to separate the crude polysaccharide solution, collect the supernatant, and filter the supernatant using a filter and filter paper to remove residual impurities;

[0021] a5. Concentrate the filtered solution at low temperature in an evaporator until the solution volume is reduced to 1 / 3 to 2 / 1 of the original volume. Add an equal volume of 80% to 100% ethanol to the concentrated solution, mix well, and let stand overnight to precipitate the polysaccharide, thus obtaining a concentrated solution of Bletilla striata polysaccharide.

[0022] a6. The precipitate is cleaned 2-3 times by static cleaning, rinsing, or ultrasonic cleaning, with each cleaning time being 1-5 minutes. The cleaned Bletilla striata polysaccharide is then placed in an oven to dry at a temperature of 40-80℃ to obtain dried Bletilla striata polysaccharide.

[0023] Furthermore, the preparation method of the pectin solution in step (1) is as follows:

[0024] a1. The pretreated citrus peel is crushed into powder, soaked in a hydrochloric acid solution of a certain concentration, and then kept in a constant temperature water bath for 60-90 minutes;

[0025] a2. Filter while hot and collect the filtrate;

[0026] a3. Add an appropriate amount of activated carbon powder to the filtrate, decolorize at 70-75℃ for 20-30 minutes, filter while hot, collect the filtrate, and repeat the operation until the filtrate is colorless;

[0027] a4. Concentrate the decolorized filtrate to 1 / 4 to 1 / 3 of its volume, then cool it.

[0028] a5. After cooling, anhydrous ethanol is added to the concentrate while stirring continuously to carry out alcohol precipitation. The amount of anhydrous ethanol added is 1 to 1.5 times the volume of the concentrate. Let it stand until no flocculent matter is precipitated. After filtration, the pectin solution is obtained.

[0029] Furthermore, the specific preparation method of the Bletilla striata pectin phospholipid complex in step (2) is as follows:

[0030] a1. The viscous mixture and lecithin were placed in a mixed organic solution of ethanol-tetrahydrofuran and reacted at a temperature of 45-55℃ for 2-3 hours.

[0031] a2. After the reaction is complete, the organic solvent is recovered under reduced pressure using a rotary evaporator, and the residual mixture is freeze-dried under vacuum for 24-48 hours; a3. The dried mixture is added to sufficient chloroform for redissolution until completely dissolved, and then filtered through a 0.22 μm organic membrane to remove unreconstituted impurities;

[0032] a4. The obtained filtrate was subjected to vacuum evaporation to recover chloroform, and then freeze-dried under vacuum for 24-48 hours to obtain the Bletilla striata pectin phospholipid complex.

[0033] Furthermore, the self-microemulsion drug delivery system in step (3) includes the following components: 0.25 to 0.5 parts by weight of ethyl oleate, 0.55 to 1.10 parts by weight of a mixed emulsifier composed of polysorbate 80 and HS15 in a mass ratio of 2:1, and 0.2 to 0.4 parts by weight of anhydrous ethanol. The self-microemulsion drug delivery system is prepared by mixing these components.

[0034] Add the Bletilla striata pectin phospholipid complex to a sufficient amount of self-microemulsion drug delivery system, sonicate for 30-60 minutes to aid dissolution, and then stir in a 37°C water bath until a stable transparent liquid is obtained.

[0035] Furthermore, in step (4), after the transparent liquid is cooled to room temperature, it is added dropwise to an aqueous solution containing carboxymethyl chitosan and acetic acid under the action of an electrostatic field. Then, an aqueous solution of sodium citrate is added, and the mixture is stirred for 1 to 5 hours for secondary cross-linking. During the electrostatic droplet process, the syringe injection speed is 0.8 mm / min, the needle type is 26G, and the stirring speed of the coagulation bath is 1200 rpm / min to obtain gel microspheres with a shell structure. Subsequently, the gel microspheres are left to stand at room temperature for 4 days to obtain microporous microspheres that have undergone gravity sedimentation.

[0036] Furthermore, in step (5), the microporous microspheres are cured under ultraviolet light for 25 minutes at a light intensity of 15 W / cm². 2The shell layer was washed away in an alkaline sodium hydroxide solution, pre-cooled in a 24°C refrigerator for 18-20 hours, and then freeze-dried in a freeze dryer for 12-48 hours to obtain the final product with a microporous structure and a self-microemulsion drug delivery system, namely, gastric mucosal surface hemostasis and repair microsphere capsules based on Bletilla striata.

[0037] This invention uses a Bletilla striata-pectin-phospholipid complex as the main component and a microemulsion drug delivery system as the drug carrier for sustained-release of Bletilla striata polysaccharides. A microcapsule with a surface-uneven structure is obtained through electrostatic freeze-drying technology. Furthermore, a reinforcing film, formed by secondary cross-linking of sodium citrate and carboxymethyl chitosan, is coated onto the surface of the microcapsule. Compared with existing technologies, the advantages of this invention are as follows:

[0038] (1) This invention combines a mixture of Bletilla striata polysaccharide pectin and lecithin in a pharmaceutical formulation. Based on the gastric mucosal repair and protection effects of Bletilla striata polysaccharide, and utilizing the water absorption and swelling properties of Bletilla striata and its self-microemulsion drug delivery system as a drug carrier, the drug can be effectively targeted to the surface of gastric ulcers. The Bletilla striata pectin phospholipid complex is targeted and aggregated at the oxidative stress-damaged site of the ulcer, rapidly forming a thin film on the ulcer surface. This film has strong adhesion and can adhere tightly to the gastric mucosa, continuously exerting hemostatic and repairing effects. Simultaneously, the viscosity and mucosal adhesion of pectin are utilized, allowing the drug to adhere more tightly to the gastric mucosa, prolonging the drug's action time and improving efficacy.

[0039] (2) The self-microemulsion drug delivery system SMEDDS in this invention is a liquid formulation composed of an oil phase, an emulsifier and a co-emulsifier. It has good mucosal permeability and biocompatibility, enabling the drug to have obvious targeted delivery to the surface of gastric ulcers. It also achieves targeted aggregation of Bletilla striata pectin phospholipid complex at the site of ulcer oxidative stress damage in a gastric ulcer-targeting manner. At the same time, it can also effectively cover the damaged gastric mucosa, reduce the stimulation of gastric acid on the gastric mucosa, and thus promote the repair of the gastric mucosa.

[0040] (3) In this invention, carboxymethyl chitosan-sodium citrate is used as the microsphere wall material, which can reduce the swelling rate of chitosan microcapsules and reduce the loss of the viscous mixture of Bletilla striata polysaccharide and pectin. The concave-convex structure of its outer shell enables precise deep drug release from the gastric mucosa, and has a highly efficient directional hemostasis and repair effect. The asymmetry and self-driving ability of the concave-convex structure of the microsphere surface can achieve good adhesion to the gastric wall and directional propulsion, making it more efficient in delivering the drug for treating gastric mucosal damage in the microsphere core, and achieving precise drug delivery. Attached Figure Description

[0041] Figure 1 This is a schematic diagram of the microstructure of the gastric mucosal surface hemostasis and repair microsphere capsules based on Bletilla striata prepared in this invention.

[0042] In the diagram: 1 - inner core layer, 2 - outermost layer. Detailed Implementation

[0043] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention is not limited to the following embodiments.

[0044] The microstructure of the gastric mucosal surface hemostasis and repair microsphere capsules based on Bletilla striata provided in this embodiment is as follows: Figure 1 As shown, the whole is spherical with an overall particle size of 8-10 μm. It is composed of an inner core layer 1 and an outermost layer 2. The inner core layer 1 is a complex of Bletilla striata polysaccharide-pectin-lecithin. The outermost layer 2 is a carboxymethyl chitosan coating layer with an uneven surface structure, as shown in the figure.

[0045] In this embodiment, the efficacy of the provided gastric mucosal surface hemostasis and repair microsphere capsules based on Bletilla striata was tested. Experiments were conducted on mice with different diseases, and the fluorescence imaging results and laser confocal microscopy fluorescence imaging results were analyzed. The results are as follows:

[0046] Compared with the control group, the fluorescently labeled Bletilla striata pectin phospholipid complex in the treatment group was concentrated on the ulcerated mucosa surface of the model rats. Furthermore, the MPO and NO contents in the gastric tissue of the treatment group were significantly reduced (P < 0.01), while the GSH level in the gastric tissue was significantly increased (P < 0.01), with stronger SOD activity and lower MDA content. The drug retention time in the stomach reached 6 hours, significantly longer than that in normal rats. Compared with the control group, the gastric mucosal surface hemostasis and repair microsphere capsules provided in this embodiment can effectively repair ulcers on the gastric surface of mice, and the difference in effect is statistically significant.

[0047] The preparation steps of the gastric mucosa surface hemostasis and repair microsphere capsules based on Bletilla striata provided in this embodiment are as follows: (1) Extraction of Bletilla striata polysaccharides

[0048] a1. Soak dried Bletilla striata stems in distilled water at a mass ratio of 1:3 to 1:10. Filter the solution through gauze to remove soluble and insoluble impurities. Collect the preliminarily cleaned Bletilla striata stems and dry them in an oven at 30 to 50°C for 18 to 24 hours.

[0049] a2. Soak the preliminarily cleaned and dried Bletilla striata stem pieces in anhydrous ethanol for 1-3 hours at a temperature of 20-30°C. Filter the mixture through gauze to remove soluble pigments. Collect the Bletilla striata stem pieces and dry them in an oven for 18-24 hours.

[0050] a3. Soak the depigmented Bletilla striata stem pieces in distilled water at a mass ratio of 1:3 to 1:10 for 0.5 to 3 hours at a temperature of 50 to 90°C. Use a magnetic stirrer to continuously stir the mixture at room temperature for about 2 hours to ensure thorough mixing. Transfer the mixture to a hot water bath and heat to 95°C, maintaining this temperature for 1 hour to improve the polysaccharide extraction efficiency. After heating, cool the mixture to room temperature.

[0051] a4 uses a centrifuge to centrifuge the mixture to separate the crude polysaccharide solution, collects the supernatant, and filters the supernatant using a filter and filter paper to remove residual plant particles and other impurities.

[0052] a5 The filtered solution was concentrated at low temperature in an evaporator until the solution volume was reduced to about 1 / 3 to 2 / 1 of the original volume. An equal volume of 80% to 100% ethanol was added to the concentrated solution, mixed well, and left to stand overnight to precipitate the polysaccharide, thus obtaining a concentrated solution of Bletilla striata polysaccharide.

[0053] The precipitate was cleaned 2-3 times by static cleaning, rinsing, or ultrasonic cleaning, with each cleaning time being 1-5 minutes. The cleaned Bletilla striata polysaccharide was then placed in an oven to dry at a temperature of 40-80℃ to obtain dried Bletilla striata polysaccharide.

[0054] (2) Preparation of Bletilla striata polysaccharide solution

[0055] A certain amount of Bletilla striata polysaccharide obtained in step (1) is added to deionized water to prepare a Bletilla striata polysaccharide solution with a mass fraction of 3-10%. The solution is stirred with a magnetic stirrer at a temperature of 50℃-70℃ for 2-4 hours to completely dissolve the Bletilla striata polysaccharide in the deionized water. The solution is then placed in a vacuum environment with a vacuum degree of -0.01 to -0.05 MPa to remove air bubbles, thus obtaining the Bletilla striata polysaccharide solution.

[0056] (3) Prepare a viscous mixture by mixing Bletilla striata polysaccharide solution with pectin.

[0057] a1. The pretreated citrus peel is crushed into powder, soaked in a hydrochloric acid solution of a certain concentration, and then kept in a constant temperature water bath for 60-90 minutes;

[0058] a2. Filter while hot and collect the filtrate;

[0059] a3. Add an appropriate amount of activated carbon powder to the filtrate, decolorize at 70-75℃ for 20-30 minutes, filter while hot, collect the filtrate, and repeat the operation until the filtrate is colorless;

[0060] a4. Concentrate the decolorized filtrate to 1 / 4 to 1 / 3 of its volume, then cool it.

[0061] a5. After cooling, anhydrous ethanol is added to the concentrated liquid while stirring continuously to carry out alcohol precipitation. The amount of anhydrous ethanol added is 1 to 1.5 times the volume of the concentrated liquid. Let it stand until no flocculent matter is precipitated. After filtration, the wet pectin solution is obtained.

[0062] a6. Once both solutions are prepared, slowly pour the Bletilla striata polysaccharide solution into the pectin solution. The Bletilla striata polysaccharide and pectin solution should be mixed in a ratio of 1:1 to 3:1. At the same time, use a magnetic stirrer to continuously stir evenly and observe the viscosity of the solution. If the required viscosity is too high, increase the proportion of Bletilla striata polysaccharide as needed.

[0063] a7. Let the well-mixed viscous mixture stand for 40-60 minutes and observe its stability and uniformity. If separation or precipitation is found, stir again or adjust the ratio.

[0064] (4) Preparation of Bletilla striata pectin phospholipid complex

[0065] a1. Place 1.0g-2.0g of the above-mentioned mixed Bletilla striata polysaccharide and pectin viscous mixture with 1.0g-2.0g of lecithin in 40-50mL of ethanol-tetrahydrofuran mixed organic solution and react at 45-55℃ for 2-3h.

[0066] a2. After the reaction is complete, the organic solvent is recovered under reduced pressure using a rotary evaporator, and the residual mixture is freeze-dried under vacuum for 24-48 hours.

[0067] a3. Add the dried mixture to 100mL~150mL of chloroform to redissolve until completely dissolved, and then filter through a 0.22μm organic membrane to remove unreconstituted impurities;

[0068] a4. The obtained filtrate was subjected to vacuum evaporation to recover chloroform, and then freeze-dried under vacuum for 24-48 hours to obtain the Bletilla striata pectin phospholipid complex.

[0069] (5) Preparation of microsphere capsules

[0070] a1. Prepare a 1g-2g self-microemulsion drug delivery system (SMEDDS) by taking 0.25g-0.5g of ethyl oleate, 0.55g-1.10g of polysorbate 80 and HS15 (mass ratio of 2:1) and 0.2g-0.4g of anhydrous ethanol.

[0071] a2. Then add 40mg-50mg of Bletilla striata pectin phospholipid complex into the microemulsion drug delivery system (SMEDDS), sonicate for 30min-60min to aid dissolution, and then stir in a 37℃ water bath until a stable transparent liquid is obtained.

[0072] a3. After cooling the cold, transparent liquid from step a2 to room temperature, the mixed solution is added dropwise to an aqueous solution containing carboxymethyl chitosan and acetic acid under an electrostatic field. Then, an aqueous solution of sodium citrate is added, and stirring is continued for 1-5 hours to perform secondary cross-linking, resulting in gel microspheres with a shell structure. During the electrostatic droplet process, the syringe injection speed is 0.8 mm / min, the needle type is 26G, and the coagulation bath stirring speed is 1200 rpm / min. Subsequently, the microspheres are allowed to stand at room temperature for 4 days to obtain surface-uneven microspheres that have undergone gravity sedimentation.

[0073] a4. The synthesized microspheres were cured under ultraviolet light for 25 min at an intensity of 15 W / cm2. The shell layer was washed off in an alkaline sodium hydroxide solution. The microspheres were then pre-cooled at -24°C for 18-20 h and freeze-dried for 12-48 h to obtain freeze-dried carboxymethyl chitosan-Bletilla striata pectin microsphere capsules with a surface texture and a self-microemulsion drug delivery system. These are Bletilla striata-based gastric mucosal surface hemostasis and repair microsphere capsules.

Claims

1. A white plant based gastric mucosal surface hemostatic repair microsphere capsule, characterized in that: The microsphere capsule is entirely spherical, and is composed of an inner core layer and an outermost layer, wherein the inner core layer is a pectin-phytosterol-egg lecithin complex; and the outermost layer is a carboxymethyl chitosan coating layer, which has a surface concave-convex structure. The microsphere capsule is prepared by the following method: (1) uniformly stirring and mixing pectin solution and phytosterol solution at a volume ratio of 1:1-3:1 to obtain a viscous mixture and allowing the mixture to stand; (2) uniformly mixing the viscous mixture and egg lecithin in an organic solvent at a mass ratio of 1:2-2:1, and then removing the organic solvent to obtain a pectin-phytosterol-egg lecithin complex; (3) adding the pectin-phytosterol-egg lecithin complex into a self-microemulsifying drug delivery system to fully dissolve the complex, and obtaining a transparent liquid; the self-microemulsifying drug delivery system comprises the following components: 0.25-0.5 parts by mass of ethyl oleate, 0.55-1.10 parts by mass of a mixed emulsifier composed of polysorbate 80 and HS15 at a mass ratio of 2:1, and 0.2-0.4 parts by mass of anhydrous ethanol, and the self-microemulsifying drug delivery system is prepared after mixing; (4) adding the transparent liquid into an aqueous solution containing carboxymethyl chitosan and acetic acid under the action of an electrostatic field, and then adding an aqueous sodium citrate solution, and continuing to stir for secondary crosslinking to obtain gel microspheres with a shell structure, and allowing the gel microspheres to stand fully in a room temperature environment to obtain surface concave-convex microspheres after gravity sedimentation; (5) curing the surface concave-convex microspheres under ultraviolet light, washing part of the sodium citrate in the shell layer in an alkaline solution, pre-cooling, and then placing the microspheres in a freeze dryer to obtain the white-baiji-based gastric mucosal surface hemostatic repair microsphere capsule.

2. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: The microsphere capsule has a particle size of 8-10 μm.

3. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: In step (1), the white-baiji polysaccharide solution is prepared as follows: adding white-baiji polysaccharide into deionized water to prepare a white-baiji polysaccharide solution with a mass fraction of 3-10%, and stirring the solution using a magnetic stirrer at a temperature of 50-70°C for 2-4 hours to completely dissolve the white-baiji polysaccharide in the deionized water, and then removing air bubbles in the solution in a vacuum environment with a vacuum degree of -0.01 to -0.05 MPa to obtain the white-baiji polysaccharide solution.

4. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 3, characterized in that: The white-baiji polysaccharide is extracted as follows: a1. soaking dry white-baiji stem blocks in distilled water at a mass ratio of 1:3-1:10, filtering the mixture with gauze to remove impurities, and collecting the preliminarily cleaned white-baiji stem blocks and drying the blocks in an oven at 30-50°C for 18-24 hours; a2. soaking the preliminarily cleaned and dried white-baiji stem blocks in anhydrous ethanol for 1-3 hours at a temperature of 20-30°C, filtering the mixture with gauze to remove soluble pigments, collecting the white-baiji stem blocks, and drying the blocks in an oven for 18-24 hours; a3. soaking the white-baiji stem blocks after removing pigments in distilled water at a mass ratio of 1:3-1:10 for 0.5-3 hours at a temperature of 50-90°C, continuously stirring the mixture at room temperature using a magnetic stirrer for about 2 hours to ensure sufficient mixing, transferring the mixture to a hot water bath, heating the mixture to 95°C, and maintaining the temperature for 1 hour, and then cooling the mixture to room temperature; a4. centrifuging the mixture to separate a crude polysaccharide solution, collecting the supernatant, and filtering the supernatant using a filter and filter paper to remove residual impurities; a5. low-temperature concentrating the filtered solution in an evaporator until the volume of the solution is reduced to 1 / 3-2 / 1 of the original volume, adding an equal volume of 80%-100% ethanol to the concentrated solution, mixing uniformly, and standing overnight to precipitate polysaccharides, thereby obtaining a concentrated white plantain polysaccharide solution; a6. washing the precipitate 2-3 times using the methods of standing washing, flushing washing, or ultrasonic washing, each time for 1-5 min, and drying the washed white plantain polysaccharide in an oven at a temperature of 40-80°C, thereby obtaining dried white plantain polysaccharide.

5. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: The preparation method of the pectin solution in step (1) is as follows: a1. crushing the pretreated citrus peel to obtain a powder, soaking the powder in a hydrochloric acid solution of a certain concentration, and then standing in a constant-temperature water bath for 60-90 min; a2. filtering while hot to collect the filtrate; a3. adding an appropriate amount of activated carbon powder to the filtrate, decolorizing at 70-75°C for 20-30 min, and then filtering while hot to collect the filtrate, and repeating the operation until the filtrate is colorless; a4. concentrating the decolorized filtrate until the volume of the filtrate is 1 / 4-1 / 3 of the original volume, and then cooling; a5. adding anhydrous ethanol to the cooled concentrated solution under constant stirring to perform alcohol precipitation, the amount of anhydrous ethanol added being 1-1.5 times the volume of the concentrated solution, standing until no flocculent material precipitates, and then filtering to obtain the pectin solution.

6. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: The specific preparation method of the white plantain pectin phospholipid complex in step (2) is as follows: a1. reacting the viscous mixture and lecithin in an ethanol-tetrahydrofuran mixed organic solution at a temperature of 45-55°C for 2-3 h; a2. after the reaction is completed, recovering the organic solvent by rotary evaporation under reduced pressure, and vacuum freeze-drying the residual mixture for 24-48 h; a3. adding sufficient chloroform to the dried mixture to completely dissolve it, and then filtering to remove uncomplexed impurities through a 0.22 μm organic membrane; a4. recovering the chloroform from the obtained filtrate by rotary evaporation under reduced pressure, and then vacuum freeze-drying for 24-48 h, thereby obtaining the white plantain pectin phospholipid complex.

7. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: In step (3), the white plantain pectin phospholipid complex is added to sufficient self-microemulsifying drug delivery system, ultrasonic treatment is performed for 30-60 min to aid dissolution, and then the mixture is placed in a 37°C water bath and stirred until a stable transparent liquid is obtained.

8. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: In step (4), after the transparent liquid is cooled to room temperature, the transparent liquid is added dropwise to a water solution in which carboxymethyl chitosan and acetic acid are dissolved under the action of an electrostatic field, a sodium citrate aqueous solution is then added, and secondary crosslinking is performed by continuing to stir for 1-5 h, the injection speed of the syringe during the electrostatic drop ball process is 0.8 mm / min, the needle type is 26G, and the stirring speed of the coagulation bath is 1200 rpm / min, thereby obtaining gel microspheres with a shell structure; subsequently, the gel microspheres are left to stand at room temperature for 4 days to obtain micro-porous microspheres that have undergone gravitational sedimentation.

9. The white psoralea based gastric mucosal surface hemostatic repair microspheres capsule according to claim 1, characterized in that: In step (5), the microporous microspheres are cured under ultraviolet light, the ultraviolet light curing time is 25 min, and the light intensity is 15 W / cm 2 The shell layer is washed away in a sodium hydroxide alkaline solution, pre-cooled in a refrigerator at-24℃ for 18h-20h, and then placed in a freeze dryer for 12h-48h to obtain the final product of the freeze-dried dry microspheres with a microporous structure and a self-microemulsifying drug delivery system, i.e., a Bletilla striata-based gastric mucosal surface hemostatic repair microsphere capsule.

10. The use of the white tuber-based gastric mucosal surface hemostasis repair microspheres in the preparation of a gastric mucosal surface repair and hemostasis drug of claim 1.

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