Oral liquid enteric capsule as well as preparation method and application thereof

Abstract

The invention provides an oral liquid enteric capsule, a preparation method and application, the capsule is an oral liquid capsule, and the capsule internally comprises mesenchymal stem cells, stem cell exosomes, laminin, fibronectin, vitreous lectin and the like. The interior of the capsule is in a liquid state, so that the activity of mesenchymal stem cells and stem cell exosomes is more favorably kept, the biological functions of the mesenchymal stem cells and the stem cell exosomes are exerted, and the repairing effect of the chemotherapy intestinal injury is better. Due to the addition of adhesion proteins such as laminin, fibronectin and vitreous lectin, the contact opportunity between the mesenchymal stem cells and the stem cell exosome and the intestinal epithelial cells can be increased, the action time is prolonged, the utilization rate of the mesenchymal stem cells and the stem cell exosome is increased to the maximum, and the effect of repairing the intestinal injury is greatly enhanced. The liquid enteric capsule can be used for treating intestinal injury caused by chemotherapy, the treatment mode is safer and more convenient, the targeting property is stronger, and the treatment effect is better.

Description

Technical Field

[0001] The invention belongs to the technical field of cell engineering and relates to an oral liquid enteric-coated capsule, a preparation method and an application thereof. Background Art

[0002] Intestinal injury is the most common side effect of chemotherapy drugs in cancer patients. It mainly causes extensive damage to the intestinal mucosa, causing diarrhea, bleeding, nausea, vomiting, abdominal pain, malnutrition, infection, and sepsis related to bacterial translocation. It not only limits the further application of chemotherapy drugs, but also causes serious physical and mental burden on patients.

[0003] At present, clinical drugs used to alleviate chemotherapy-induced intestinal injury mainly include ondansetron, loperamide, olanzapine, etc., which have single efficacy and large side effects. Research on the prevention and treatment of chemotherapy-induced intestinal injury with traditional Chinese medicine is still in its infancy. A large number of studies have shown that mesenchymal stem cells (MSCs) can repair damaged tissues by reducing cell apoptosis, alleviating inflammatory stress response, promoting angiogenesis, inhibiting fibrosis, immunosuppression, and releasing trauma repair factors. MSC exosomes contain proteins, lipids, mRNA, miRNA, etc., as well as a variety of active ingredients such as EGF, VEGF, HGF, etc. These ingredients can communicate with target cells, promote cell proliferation, migration or inhibit cell apoptosis, thereby achieving the purpose of promoting tissue damage repair.

[0004] MSCs and exosomes are generally used for body treatment through intravenous infusion, but under this treatment method, MSCs and exosomes will be diluted after entering the blood circulation. In particular, MSCs will be intercepted by the lungs, liver, and spleen, and the number that reaches the damaged area is very small, and the treatment effect is limited. Summary of the invention

[0005] The purpose of the present invention is to provide an oral liquid enteric-coated capsule, a preparation method and an application thereof, so as to solve the problem that MSCs and exosomes have poor effects in treating intestinal damage.

[0006] To achieve the above object, the present invention adopts the following technical solutions: The present application provides a method for preparing an oral liquid enteric-coated capsule, the method comprising: S01: Add sodium carboxymethyl cellulose, calcium chloride, laminin, fibronectin, and vitreous lectin into PBS buffer, mix well, then add mesenchymal stem cells and stem cell exosomes, stir well to form capsule contents.

[0007] According to the mass volume ratio, 5-15 mg / mL sodium carboxymethyl cellulose, 3-30 mg / mL calcium chloride, 20-80 ng / mL laminin, 10-50 ng / mL fibronectin, and 10-30 ng / mL vitreous agglutinin were added to PBS buffer, mixed evenly, and then 1-5×10 6 / mL mesenchymal stem cells and 3-7×10 7 / mL stem cell exosomes, stir evenly to form capsule contents.

[0008] Preferably, the mass volume ratio of each component raw material in the capsule content is 10 mg / mL sodium carboxymethyl cellulose, 15 mg / mL calcium chloride, 50 ng / mL laminin, 30 ng / mL fibronectin, 20 ng / mL vitreous agglutinin, 3×10 6 / mL mesenchymal stem cells and 5×10 7 / mL stem cell exosomes. Mesenchymal stem cells and stem cell exosomes are P2-P5 generation stem cells and exosomes.

[0009] Laminin and fibronectin exist in various basement membranes and play an important role in the adhesion and migration of cells. The addition of laminin and fibronectin can increase the contact between mesenchymal stem cells and stem cell exosomes and intestinal epithelial cells under the action of viscosity, prolong the action time of mesenchymal stem cells and stem cell exosomes, and thus achieve the purpose of enhancing the therapeutic effect of intestinal injury.

[0010] S02: Dissolve sodium alginate in distilled water and cool to room temperature to form a sodium alginate solution.

[0011] Sodium alginate is added to distilled water, stirred in a constant temperature water bath at 40°C until the sodium alginate is completely dissolved, and cooled to room temperature to form a sodium alginate solution. In the present application, the concentration of the sodium alginate solution is 5-30 mg / mL, preferably 20 mg / mL.

[0012] S03: dropping the capsule contents into the continuously stirred sodium alginate solution at a rate of 1 mL / min to form a primary capsule.

[0013] The capsule contents are dripped into a sodium alginate solution that is continuously stirred by magnetic force at a rate of 1 mL / min, so that the calcium chloride in the capsule contents reacts with the sodium alginate to form a primary capsule. The primary capsule contains sodium carboxymethyl cellulose, adhesion protein, fibronectin, vitreous lectin, mesenchymal stem cells and stem cell exosomes.

[0014] S04: filtering out the primary capsules, washing with physiological saline, and then placing them in a calcium chloride solution for solidification for 30-40 minutes to obtain solidified capsules.

[0015] After filtering out the primary capsule, the primary capsule is quickly washed with physiological saline, and then placed in a calcium chloride solution with a concentration of 10-30 mg / mL to further solidify the primary capsule with calcium chloride for 30-40 minutes to obtain a solidified capsule. Preferably, the concentration of the calcium chloride solution is 20 mg / mL.

[0016] S05: Add triethyl citrate and talc to the enteric resin and homogenize for 10 minutes to obtain an enteric coating solution.

[0017] Add triethyl citrate and talc to the enteric resin, and use a high shear homogenizer to fully homogenize for 10 minutes to obtain an enteric coating solution. Wherein, the enteric resin is Eudragit L30-55, and the addition amounts of triethyl citrate and talc are 50-150 mg / mL and 300-500 mg / mL, respectively, by mass volume ratio. Preferably, the addition amounts of triethyl citrate and talc are 100 mg / mL and 400 mg / mL, respectively, by mass volume ratio.

[0018] S06: coating the solidified capsules with the enteric coating liquid by a fluidized bed coating method, and obtaining oral liquid enteric capsules after drying.

[0019] The fluidized bed coating method is used to coat the solidified capsules with the enteric coating liquid according to the parameters of air volume 80-120HZ, atomization pressure 0.8-2bar, air inlet temperature 30-37℃, material temperature 25-30℃, and spray speed 5-10g / min / Kg. After the coating treatment is completed, it is dried for 0.5h to obtain oral liquid enteric capsules.

[0020] The present invention has the following beneficial effects: (1) This application makes mesenchymal stem cells and stem cell exosomes into an orally administrable liquid enteric-coated capsule, which breaks the conventional use method of mesenchymal stem cells and stem cell exosomes such as intravenous infusion. The capsule is liquid, which is more conducive to maintaining the activity of mesenchymal stem cells and stem cell exosomes and exerting their biological functions, and has a better repair effect on chemotherapy-induced intestinal damage.

[0021] (2) The addition of adhesion proteins such as laminin, fibronectin and vitreous lectin can increase the contact between mesenchymal stem cells, stem cell exosomes and intestinal epithelial cells, prolong the action time, and maximize the utilization rate of mesenchymal stem cells and stem cell exosomes, thereby greatly enhancing the effect of repairing intestinal damage.

[0022] (3) The liquid enteric-coated capsules can be used to prepare and treat intestinal damage caused by chemotherapy. The treatment method is safer, more convenient, more targeted, and has better therapeutic effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a picture of the actual appearance of the oral liquid enteric-coated capsule prepared in Example 1; Figure 2 This is a diagram showing the digestion of the oral liquid enteric-coated capsules prepared in Example 1 in artificial gastric juice; Figure 3 This is a diagram showing the digestion of the oral liquid enteric-coated capsules prepared in Example 1 in artificial intestinal fluid; Figure 4 This is a graph showing the effect of the oral liquid enteric-coated capsules prepared in Example 1 on serum DAO in mice with intestinal damage induced by pentafluorouracil; Figure 5 This is a graph showing the effect of the oral liquid enteric-coated capsules prepared in Example 1 on serum TNF-α in mice with intestinal damage induced by pentafluorouracil; Figure 6 This is a graph showing the effect of the oral liquid enteric-coated capsules prepared in Example 1 on serum IL6 in mice with intestinal damage induced by pentafluorouracil; Figure 7 This is a graph showing the effect of the oral liquid enteric-coated capsule prepared in Example 1 on the transcription level of gene Zo1 in mice with intestinal damage induced by pentafluorouracil; Figure 8 This is a graph showing the effect of the oral liquid enteric-coated capsules prepared in Example 1 on the transcription level of the gene Occludin in mice with intestinal damage induced by pentafluorouracil; Fig. 9 This is a graph showing the effect of the oral liquid enteric-coated capsules prepared in Example 1 on the pathological changes in the small intestine of mice with intestinal injury induced by 5-fluorouracil, wherein the magnification is 200 times, A is the normal group, B is the model group, C is the capsule (without adhesion protein) group, and D is the capsule group. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further explained and illustrated by means of specific embodiments below.

[0025] Example 1 The present application embodiment provides an oral liquid enteric-coated capsule, and the preparation method of the capsule comprises: S101: According to the mass volume ratio, 10 mg / mL sodium carboxymethyl cellulose, 15 mg / mL calcium chloride, 50 ng / mL laminin, 30 ng / mL fibronectin, and 20 ng / mL vitreous agglutinin were added to PBS buffer, mixed evenly, and then 3×10 6 / mL mesenchymal stem cells and 5×10 7 / mL stem cell exosomes, stir evenly to form capsule contents.

[0026] S102: Add sodium alginate to distilled water, stir in a constant temperature water bath at 40°C until the sodium alginate is completely dissolved, and cool to room temperature to form a sodium alginate solution with a concentration of 20 mg / mL.

[0027] S103: dropping the capsule contents into the sodium alginate solution which is continuously stirred by magnetic force at a rate of 1 mL / min, so that the calcium chloride in the capsule contents reacts with the sodium alginate to form a primary capsule.

[0028] S104: After filtering out the primary capsules, the primary capsules are quickly washed with physiological saline, and then placed in a calcium chloride solution with a concentration of 20 mg / mL, so that the calcium chloride further solidifies the primary capsules for 30 minutes to obtain solidified capsules.

[0029] S105: Add triethyl citrate and talc to the enteric resin Eudragit L30-55, and fully homogenize for 10 minutes using a high shear homogenizer to obtain an enteric coating solution, wherein the mass volume ratio of triethyl citrate to talc is 100 mg / mL and 400 mg / mL, respectively.

[0030] S106: The fluidized bed coating method is used to coat the solidified capsules with the enteric coating liquid according to the parameters of air volume 100 Hz, atomization pressure 1.2 bar, air inlet temperature 35°C, material temperature 28°C, and spray speed 8 g / min / kg. After the coating treatment is completed, the solidified capsules are dried for 0.5 hours to obtain oral liquid enteric capsules.

[0031] Example 2 The present application embodiment provides an oral liquid enteric-coated capsule, and the preparation method of the capsule comprises: S201: According to the mass volume ratio, 5 mg / mL sodium carboxymethyl cellulose, 10 mg / mL calcium chloride, 20 ng / mL laminin, 50 ng / mL fibronectin, and 10 ng / mL vitreous agglutinin were added to PBS buffer, mixed evenly, and then 1×10 6 / mL mesenchymal stem cells and 7×10 7 / mL stem cell exosomes, stir evenly to form capsule contents.

[0032] S202: Add sodium alginate to distilled water, stir in a constant temperature water bath at 40°C until the sodium alginate is completely dissolved, and cool to room temperature to form a sodium alginate solution with a concentration of 5 mg / mL.

[0033] S203: dropping the capsule contents into the sodium alginate solution which is continuously stirred by magnetic force at a rate of 1 mL / min, so that the calcium chloride in the capsule contents reacts with the sodium alginate to form a primary capsule.

[0034] S204: After filtering out the primary capsules, the primary capsules are quickly washed with physiological saline, and then placed in a calcium chloride solution with a concentration of 10 mg / mL, so that the calcium chloride further solidifies the primary capsules for 40 minutes to obtain solidified capsules.

[0035] S205: Add triethyl citrate and talc to the enteric resin Eudragit L30-55, and fully homogenize for 10 minutes using a high shear homogenizer to obtain an enteric coating solution, wherein the mass volume ratio of triethyl citrate to talc is 50 mg / mL and 350 mg / mL, respectively.

[0036] S206: The fluidized bed coating method is used to coat the solidified capsules with the enteric coating liquid according to the parameters of air volume 80HZ, atomization pressure 0.8bar, air inlet temperature 30°C, material temperature 25°C, and spray speed 5g / min / kg. After the coating treatment is completed, the capsules are dried for 0.5h to obtain oral liquid enteric capsules.

[0037] Example 3 The present application embodiment provides an oral liquid enteric-coated capsule, and the preparation method of the capsule comprises: S301: According to the mass volume ratio, 15 mg / mL sodium carboxymethyl cellulose, 3 mg / mL calcium chloride, 80 ng / mL laminin, 20 ng / mL fibronectin, and 30 ng / mL vitreous agglutinin were added to PBS buffer, mixed evenly, and then 5×10 6 / mL mesenchymal stem cells and 3×10 7 / mL stem cell exosomes, stir evenly to form capsule contents.

[0038] S302: Add sodium alginate to distilled water, stir in a constant temperature water bath at 40°C until the sodium alginate is completely dissolved, and cool to room temperature to form a sodium alginate solution with a concentration of 30 mg / mL.

[0039] S303: dropping the capsule contents into the sodium alginate solution which is continuously stirred by magnetic force at a rate of 1 mL / min, so that the calcium chloride in the capsule contents reacts with the sodium alginate to form a primary capsule.

[0040] S304: After filtering out the primary capsule, the primary capsule is quickly washed with physiological saline, and then placed in a calcium chloride solution with a concentration of 30 mg / mL, so that the calcium chloride further solidifies the primary capsule for 35 minutes to obtain a solidified capsule.

[0041] S305: Add triethyl citrate and talc to the enteric resin Eudragit L30-55, and fully homogenize for 10 minutes using a high shear homogenizer to obtain an enteric coating solution, wherein the mass volume ratio of triethyl citrate and talc is 150 mg / mL and 500 mg / mL, respectively.

[0042] S306: The fluidized bed coating method is used to coat the solidified capsules with the enteric coating liquid according to the parameters of air volume 120HZ, atomization pressure 2bar, air inlet temperature 37°C, material temperature 30°C, and spray speed 10g / min / Kg. After the coating treatment is completed, the capsules are dried for 0.5h to obtain oral liquid enteric capsules.

[0043] Example 4 The present application embodiment provides an oral liquid enteric-coated capsule, and the preparation method of the capsule comprises: S401: According to the mass volume ratio, 12 mg / mL sodium carboxymethyl cellulose, 30 mg / mL calcium chloride, 60 ng / mL laminin, 10 ng / mL fibronectin, and 30 ng / mL vitreous agglutinin were added to PBS buffer, mixed evenly, and then 2×10 6 / mL mesenchymal stem cells and 4×10 7 / mL stem cell exosomes, stir evenly to form capsule contents.

[0044] S402: Add sodium alginate to distilled water, stir in a constant temperature water bath at 40°C until the sodium alginate is completely dissolved, and cool to room temperature to form a sodium alginate solution with a concentration of 25 mg / mL.

[0045] S403: dropping the capsule contents into the sodium alginate solution which is continuously stirred by magnetic force at a rate of 1 mL / min, so that the calcium chloride in the capsule contents reacts with the sodium alginate to form a primary capsule.

[0046] S404: After filtering out the primary capsule, the primary capsule is quickly washed with physiological saline, and then placed in a calcium chloride solution with a concentration of 25 mg / mL, so that the calcium chloride further solidifies the primary capsule for 30 minutes to obtain a solidified capsule.

[0047] S405: Add triethyl citrate and talc to the enteric resin Eudragit L30-55, and fully homogenize for 10 minutes using a high shear homogenizer to obtain an enteric coating solution, wherein the mass volume ratio of triethyl citrate and talc is 100 mg / mL and 300 mg / mL, respectively.

[0048] S406: The fluidized bed coating method is used to coat the solidified capsules with the enteric coating liquid according to the parameters of air volume 110HZ, atomization pressure 1.5bar, air inlet temperature 36°C, material temperature 28°C, and spray speed 9g / min / Kg. After the coating treatment is completed, the capsules are dried for 0.5h to obtain oral liquid enteric capsules.

[0049] The oral liquid enteric-coated capsules prepared in Example 1 were compared with a measuring ruler and photographed. Figure 1 . Figure 1 It can be seen that the oral liquid enteric-coated capsule is a translucent, spherical capsule with a diameter of about 1.5-2 mm.

[0050] The present application also uses the oral liquid enteric-coated capsules prepared in Example 1 as an example to conduct in vitro simulated release tests in gastric juice and intestinal juice, respectively, to detect the release of the oral liquid enteric-coated capsules in gastric juice and intestinal juice. The specific contents are as follows: 1. Prepare artificial gastric juice Add 23.40 mL of concentrated hydrochloric acid to 100 mL of water to prepare dilute hydrochloric acid. Take 1.64 mL of dilute hydrochloric acid, dilute it to 100 mL with water, mix well, and obtain artificial gastric juice with a pH value of about 2.

[0051] 2. Prepare artificial intestinal fluid Dissolve 0.68 g of potassium dihydrogen phosphate in 50 mL of water, add 0.1 mol / L sodium hydroxide solution dropwise into the potassium dihydrogen phosphate aqueous solution, measure the pH of the solution with a pH meter while stirring with a glass rod until the pH is 6.8. Dilute with water to 100 mL to obtain artificial intestinal fluid with a pH value of about 6.8.

[0052] 3. Simulation experiment 20 oral liquid enteric-coated capsules prepared in Example 1 were placed in 25 mL of artificial gastric juice and kept at 37° C. for 2 h. The dissolution of the capsules was observed to obtain the attached Figure 2 After filtering out the artificial gastric juice, transfer 20 oral liquid enteric-coated capsules into 25 mL of artificial intestinal juice and continue to keep warm at 37°C. After 30 minutes, observe the dissolution of the capsules to obtain the attached Figure 3 .

[0053] By the attached Figure 2 It can be seen that after being immersed in artificial gastric juice for 2 hours, the oral liquid enteric-coated capsules prepared in Example 1 did not dissolve. Figure 3It can be seen that after 30 minutes of artificial intestinal fluid immersion, the oral liquid enteric-coated capsules prepared in Example 1 were completely dissolved. This shows that the oral liquid enteric-coated capsules prepared in the examples of the present application can resist digestion by gastric juice and prevent gastric juice from damaging the mesenchymal stem cells, stem cell exosomes, laminin and fibronectin inside the capsule. At the same time, the oral liquid enteric-coated capsules can quickly dissolve in the intestinal fluid and completely release the contents such as mesenchymal stem cells and stem cell exosomes.

[0054] In order to verify the effectiveness of the oral liquid enteric-coated capsules prepared in the examples of the present application in treating intestinal injury, a pentafluorouracil intestinal injury model was established in the examples of the present application and oral liquid enteric-coated capsules were gavage-fed to observe intestinal injury-related indicators.

[0055] Specifically, 24 male ICR mice weighing 18-22g and SPF grade were selected. Before the experiment, all mice were adaptively fed for 1 week under a 12h light / dark cycle, a relative humidity of 60±5% and a relative temperature of 25±2°C, and then divided into 4 groups: normal group, model group, capsule (no adhesion protein) group, and capsule group, with 6 mice in each group, and the treatment cycle was 7d. Among them, the normal group was not treated and fed normally. In the model group, 30 mg / kg of fluorouracil was injected intraperitoneally for the first 4 days, and then fed normally for the next 3 days. In the capsule (no adhesion protein) group, 30 mg / kg of fluorouracil was injected intraperitoneally for the first 4 days, and oral liquid enteric-coated capsules without adhesion protein were gavaged every day, at a dose of 10 capsules / mouse / day, for a total of 7d. In the capsule group, 30 mg / kg of fluorouracil was injected intraperitoneally for the first 4 days, and oral liquid enteric-coated capsules prepared in Example 1 were gavaged every day, at a dose of 10 capsules / mouse / day, for a total of 7d.

[0056] After feeding, remove the eyeballs to collect whole blood, and incubate in a 37℃ water bath for 1 hour. After incubation, centrifuge to collect serum and store at -80℃. Take intestinal tissue and immediately freeze it in liquid nitrogen. Take a part of the small intestine, rinse it with saline and store it in 4% paraformaldehyde.

[0057] ELISA kits were used to detect the levels of DAO (diamine oxidase), TNF-α (tumor necrosis factor-α), and IL-6 (interleukin-6) in the serum of each group of mice. The results are shown in the attached Figure 4-6 As shown. Figure 4-6It can be seen that the DAO, TNF-α and IL-6 levels of mice in the model group were the highest, followed by the capsule (no adhesion protein) group, and the capsule group had the lowest levels. In other words, oral liquid enteric capsules can effectively reduce the reduction of DAO, TNF-α and IL-6 levels in mouse serum induced by pentafluorouracil, and the reduction effect of the capsule group with adhesion proteins such as adhesion protein and fibronectin is better than that of the capsule (no adhesion protein) group. This shows that mesenchymal stem cells and stem cell exosomes can significantly alleviate the occurrence of intestinal mechanical barrier damage and inflammation caused by pentafluorouracil, and the addition of adhesion proteins in the capsule can greatly increase this effect.

[0058] Fluorescence quantitative PCR was used to detect the transcription levels of Zo1 and Occludin genes in intestinal tissues. The results are shown in the attached figure. Figure 7 , 8 As shown. Figure 7 , 8 It can be seen that the transcription levels of Zo1 and Occludin genes in the model group, capsule (no adhesion protein) group, and capsule group gradually increased. This indicates that mesenchymal stem cells and stem cell exosomes should be able to increase the expression of tight junction proteins ZO1 and OCCLUDIN, thereby closing the paracellular gap between epithelial cells, preventing solutes such as microorganisms and antigens from leaking when passing through epithelial cells, maintaining the functional integrity of the intestinal mucosa, and thus enhancing the intestinal barrier function. At the same time, the addition of adhesion proteins to the capsule can significantly enhance the above functions of MSCs and exosomes.

[0059] In addition, paraffin sections of small intestinal tissue were made and HE staining was performed to observe the pathological changes of intestinal tissue. Fig. 9 . Fig. 9 It can be seen that the villi of the small intestine of the mice in the normal group were arranged neatly, and the structures of each layer were normal; the villi of the small intestine of the mice in the model group fell off, were sparsely arranged, the structures of each layer were severely damaged, and the number of small intestinal glands decreased; compared with the model group, the number of small intestinal villi in the capsule (no adhesion protein) group and the capsule group mice increased significantly, and were arranged relatively neatly. The degree of damage to the structures of each layer was alleviated, and the number of small intestinal glands increased, especially the small intestinal structure of the mice in the capsule group was very similar to that of the normal group.

[0060] The above experimental studies have demonstrated that the oral liquid enteric-coated capsules prepared in the examples of the present application are very effective in treating intestinal damage caused by chemotherapy, especially the addition of adhesive proteins in the enteric-coated capsules, which greatly enhances the therapeutic effect of intestinal damage.

[0061] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing an oral liquid enteric-coated capsule, characterized in that: include: Sodium carboxymethylcellulose, calcium chloride, laminin, fibronectin, and vitreous lectin are added to PBS buffer, mixed well, and then mesenchymal stem cells and stem cell exosomes are added and stirred evenly to form capsule contents; Dissolve sodium alginate in distilled water and cool to room temperature to form a sodium alginate solution; The capsule contents are dripped into the continuously stirred sodium alginate solution at a rate of 1 mL / min to form a primary capsule; The primary capsules are filtered out, washed with physiological saline, and then placed in a calcium chloride solution for curing for 30-40 minutes to obtain cured capsules; Add triethyl citrate and talc to the enteric resin and homogenize for 10 minutes to obtain an enteric coating solution; The enteric coating liquid is used to coat the solidified capsules by a fluidized bed coating method, and oral liquid enteric capsules are obtained after drying.

2. The method for preparing the oral liquid enteric-coated capsule according to claim 1, characterized in that: According to the mass volume ratio, the capsule contents include 5-15 mg / mL sodium carboxymethyl cellulose, 3-30 mg / mL calcium chloride, 20-80 ng / mL laminin, 10-50 ng / mL fibronectin, 10-30 ng / mL vitreous agglutinin, 1-5×10 6 / mL mesenchymal stem cells and 3-7×10 7 / mL stem cell exosomes.

3. The method for preparing the oral liquid enteric-coated capsule according to claim 2, characterized in that: According to the mass volume ratio, the capsule contents include 10 mg / mL sodium carboxymethyl cellulose, 15 mg / mL calcium chloride, 50 ng / mL laminin, 30 ng / mL fibronectin, 20 ng / mL vitreous agglutinin, 3×10 6 / mL mesenchymal stem cells and 5×10 7 / mL stem cell exosomes.

4. The method for preparing the oral liquid enteric-coated capsule according to claim 1, characterized in that: The concentration of the sodium alginate solution is 5-30 mg / mL.

5. The method for preparing the oral liquid enteric-coated capsule according to claim 4, characterized in that: The concentration of the sodium alginate solution is 20 mg / mL.

6. The method for preparing the oral liquid enteric-coated capsule according to claim 1, characterized in that: The concentration of the calcium chloride solution is 10-30 mg / mL.

7. The method for preparing the oral liquid enteric-coated capsule according to claim 1, characterized in that: According to the mass volume ratio, the added amounts of triethyl citrate and talc are 50-150 mg / mL and 300-500 mg / mL respectively.

8. The method for preparing the oral liquid enteric-coated capsule according to claim 1, characterized in that: The parameters of fluidized bed coating are: air volume 80-120HZ, atomization pressure 0.8-2bar, inlet air temperature 30-37℃, material temperature 25-30℃, spray speed 5-10g / min / Kg.

9. An oral liquid enteric-coated capsule, characterized in that: Prepared according to any one of claims 1-8.

10. The oral liquid enteric-coated capsules prepared by any one of the methods of claims 1 to 8 are used for preparing drugs for treating intestinal damage caused by chemotherapy.

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