An oral colon-targeted silicon nanomedicine and its application

Abstract

The present invention discloses an oral colon-targeted silicon nanomedicine and its application, which belongs to the technical field of drug targeted delivery. The present invention is an oral colon-targeted delivery system based on biodegradable nano-silica, and the drug molecules can be simultaneously encapsulated during the preparation process, and hyaluronic acid is modified on the surface to enhance its targeting effect on inflammatory endothelial cells and macrophages. In order to ensure the stability of the delivery system in the gastrointestinal tract and avoid the influence of the strong acid environment and enzymes in the stomach on proteins, chitosan and sodium alginate are further modified on its surface through electrostatic effects. Hyaluronic acid, chitosan and sodium alginate are natural polymer materials with good biocompatibility. The present invention uses the new neurotrophic factor MANF as a model protein, and successfully delivers the MANF protein to the colon part by constructing an oral colon-targeted delivery system, and confirms at the animal level that it can improve ulcerative colitis damage through oral administration.

Description

Technical Field

[0001] The present invention belongs to the technical field of drug targeted delivery, and in particular relates to an oral colon-targeted silicon nanomedicine. Background Art

[0002] Ulcerative colitis is one of the leading causes of inflammatory bowel disease (IBD). Its numerous triggering factors, unclear pathogenesis, and difficult clinical treatment are common, with frequent relapses. The World Health Organization has designated it as one of the most intractable diseases in modern times. Common routes of administration for ulcerative colitis include oral, subcutaneous, intramuscular, or intravenous injections. Oral administration avoids the potential infection and pain associated with injections, offers significant convenience, and improves patient compliance.

[0003] Currently, the treatments for ulcerative colitis include aminosalicylic acid, glucocorticoids, immunosuppressants, and biologics. However, current drugs have many shortcomings. For example, aminosalicylic acid drugs have significant side effects, mainly including nausea, vomiting, and other adverse reactions; long-term use of glucocorticoids can cause symptoms such as edema, gastrointestinal ulcers, and even gastrointestinal bleeding. With the increasing number of patients with ulcerative colitis in recent years, biologics have gradually been used to treat ulcerative colitis, and are superior to traditional therapies (such as infliximab) in reducing disease recurrence and relieving pain. Biologics are mainly injected into the tail vein and have a rapid onset of action, but are prone to allergies and other adverse reactions. Biologics such as proteins, peptides, and antibodies are easily degraded under the harsh conditions of the gastrointestinal tract, and oral delivery is challenging. Therefore, it is of great significance to construct an oral targeted delivery system for biologics. Summary of the Invention

[0004] To address the shortcomings of existing technologies for the oral targeted delivery of biological agents for ulcerative colitis, the present invention provides an oral colon-targeted silica nanoparticle drug. Using the novel neurotrophic factor MANF as a model protein, the present invention constructs an oral colon-targeted delivery system to successfully deliver MANF protein to the colon. Animal studies have demonstrated that oral administration can improve ulcerative colitis damage. Specifically, the present invention utilizes the following technical solutions:

[0005] The oral colon-targeted silicon nanomedicine of the present invention comprises silicon dioxide nanoparticles loaded with MANF, wherein the silicon dioxide nanoparticles loaded with MANF are biodegradable silicon nanoparticles (MBS).

[0006] Preferably, the preparation method of the biodegradable silicon nanoparticles is to mix cyclohexane, n-hexanol and Triton X-100 evenly, then add 1-10 mg / mL MANF protein solution, TEOS, and BTEPDS and mix evenly, then add 20%-30% ammonia water and stir overnight, use acetone to precipitate the nanoparticles, disperse the nanoparticles in a mixed solution of ethanol and APTES (3-aminopropyltriethoxysilane), and stir for 6-15 hours to obtain amino-functionalized biodegradable silicon nanoparticles.

[0007] In the preparation method, preferably, the volume ratio of cyclohexane, n-hexanol, and Triton X-100 is 20-25:5-6:5-6. The concentration of the MANF protein solution is 1-5 mg / mL. The volume ratio of the MANF protein solution, TEOS, and BTEPDS is 5-15:2-3:2-3. The volume ratio of ethanol and APTES is 300-600:1.

[0008] As a more preferred embodiment, the oral colon-targeted silicon nanomedicine described in the present invention, wherein the preparation method of the amino-functionalized silicon nanoparticles with disulfide bonds is as follows: 20-25 mL of cyclohexane, 5-6 mL of n-hexanol and 5-6 mL of Triton X-100 are mixed evenly, and stirred for 0.5-1 hour, then 0.5-1.5 mL of 1-5 mg / mL MANF protein solution, 0.2-0.3 mL of TEOS, and 0.2-0.3 mL of BTEPDS are added to the above mixed solution and mixed evenly, 0.16-0.20 mL of 20%-30% ammonia water is added to the system and stirred overnight, after which the reaction is completed, the nanoparticles are precipitated using 20-50 mL of acetone, and finally, the prepared nanoparticles are dispersed in a mixed solution of 30-60 mL of ethanol and 100 μL of APTES, stirred, and collected by centrifugation.

[0009] Furthermore, the amino-functionalized silicon nanoparticles with disulfide bonds were prepared by mixing 22.5 mL of cyclohexane, 5.4 mL of n-hexanol, and 5.3 mL of Triton X-100, stirring for 0.5 h, then adding 0.9 mL of a 3 mg / mL MANF protein solution, 0.24 mL of TEOS, and 0.225 mL of BTEPDS to the mixed solution, and mixing evenly. 0.18 mL of 25% ammonia water was added to the system and stirred overnight. After the reaction was completed, the nanoparticles were precipitated with 30 mL of acetone. Finally, the prepared nanoparticles were dispersed in a mixed solution of 50 mL of ethanol and 100 μL of APTES and stirred for 10 h.

[0010] As a preferred embodiment, the oral colon-targeted silicon nanoparticles of the present invention also include hyaluronic acid coated on the silicon dioxide nanoparticles. Specifically, the silicon dioxide nanoparticles prepared above can be added to a 5-15 mg / mL hyaluronic acid aqueous solution and stirred for 0.2-3 hours to obtain hyaluronic acid-modified MBS nanoparticles (MBSH). Furthermore, chitosan and sodium alginate layers coated on the outside of the MBSH particles are also included. Specifically, the silicon dioxide nanoparticles (MBSH) modified with hyaluronic acid (Hyaluronan) can be reacted with 1-5 mg / mL chitosan solution and 1-3 mg / mL sodium alginate solution for 0.2-3 hours to obtain an oral colon-targeted silicon composite nanoparticle MBSH@CA double-layer coated with chitosan (Chitosan) and sodium alginate (Alginate sodium).

[0011] The present invention prepares an oral colon-targeted delivery system based on biodegradable nano-silica, and the drug molecules can be simultaneously encapsulated during the preparation process. Hyaluronic acid is surface-modified to enhance its targeting effect on inflammatory endothelial cells and macrophages. In order to ensure the stability of the delivery system in the gastrointestinal tract and avoid the influence of the strong acid environment and enzymes in the stomach on proteins, chitosan and sodium alginate are further modified on its surface through electrostatic effects. Hyaluronic acid, chitosan and sodium alginate are natural polymer materials with good biocompatibility. CD44 is highly expressed on the surface of endothelial cells and macrophages in the inflammatory area of ​​colitis, and hyaluronic acid can specifically target CD44 molecules. Sodium alginate and chitosan are pH-responsive polymer materials that can release drugs in the colon environment.

[0012] On the other hand, the oral colon-targeted silicon nanoparticles of the present invention can be used to prepare pharmaceutical preparations for treating ulcerative colitis. The silicon nanomaterials of the present invention have high drug encapsulation efficiency and drug loading capacity, are easy to modify on the surface, and can form multifunctional silicon nanoparticles.

[0013] In this invention, tetraethyl orthosilicate (TEOS) and bis-[3-(triethoxysilyl)propyl]-disulfide (BTEPDS) serve as the silicon source, and the resulting silica nanoparticles contain disulfide bonds. Once internalized by inflammatory macrophages, the disulfide bonds cleave in the presence of intracellular glutathione (GSH), releasing the protein. Furthermore, the nanomedicine preparation process is performed at room temperature.

[0014] The present invention provides an oral colon-targeted silicon nanomedicine, which uses the novel neurotrophic factor MANF as a model protein. By constructing an oral colon-targeted delivery system, the MANF protein is successfully delivered to the inflammatory area of ​​the colon, and it is confirmed at the animal level that it can improve ulcerative colitis damage through oral administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 : Schematic diagram of the preparation of oral silicon nanomedicine and its therapeutic effect on ulcerative colitis mice.

[0016] Figure 2 : Transmission electron microscopy and potential maps of silicon nanoparticles. (A) MBS nanoparticles, (B) MBSH nanoparticles, (C) MBSH@CA nanoparticles, (D) potential analysis.

[0017] Figure 3 In vitro simulated drug release profiles of silicon nanoparticles. (A) MANF release profiles from MBSH@CA nanoparticles at different GSH concentrations. (B) MANF release profiles from MBS nanoparticles and MBSH@CA nanoparticles in simulated gastrointestinal buffer solutions. Insets are magnified images of the rectangular regions, showing simulated gastric fluid (SGF) for 2 hours, simulated small intestinal fluid (SIF) for 6 hours, and simulated colonic fluid (SCF) for 52 hours.

[0018] Figure 4 Targeting evaluation of silicon nanomedicines. In vivo fluorescence imaging of normal mice and mice with DSS-induced colitis after oral administration of BS@CA, BSH@CA, MBS@CA, and MBSH@CA nanoparticles and corresponding gastrointestinal tissue fluorescence imaging.

[0019] Figure 5 Preliminary evaluation of the biocompatibility of silicon nanomedicines. C57 mice were orally administered with PBS, BS@CA, BSH@CA, MBS@CA, or MBSH@CA nanoparticles daily for 7 consecutive days. (A) Body weight; (B) Routine blood test; (C) HE staining. Scale bar represents 200 μm.

[0020] Figure 6 Results of the efficacy evaluation of silicon nanomedicines for ulcerative colitis. (A) Schematic diagram of the experimental design, ig stands for oral gavage; (B) Body weight change; (C) DAI score; (D) Colon length; (E) Spleen weight; (F) Photos of the colon and spleen; (G) HE staining images.

[0021] Figure 7 Changes in serum proinflammatory cytokine and MPO levels in experimental animals. (A) IL-6, (B) IL-1β, (C) TNF-α, (D) MPO. Data are expressed as mean ± standard deviation. *p < 0.05, ***p < 0.001, ****p < 0.0001 compared with the DSS group. DETAILED DESCRIPTION

[0022] The following embodiments are further descriptions of the present invention to illustrate the technical content of the present invention, but the essential content of the present invention is not limited to the following embodiments. Ordinary technicians in this field can and should know that any simple changes or replacements based on the essential spirit of the present invention should fall within the scope of protection required by the present invention.

[0023] Example 1:

[0024] Preparation of Oral Colon-Targeted Silica Nanomedicines:

[0025] (1) First, 22.5 mL of cyclohexane, 5.4 mL of n-hexanol, and 5.3 mL of Triton X-100 were mixed evenly and stirred using a magnetic stirrer at a speed of 700 rpm / min for 0.5 h.

[0026] (2) 0.9 mL of 3 mg / mL recombinant human MANF protein solution (preparation reference CN112587654A Application of brain astrocyte-derived neurotrophic factor in the treatment of ulcerative colitis), 0.24 mL of tetraethyl orthosilicate (TEOS), and 0.225 mL of bis-[3-(triethoxysilyl)propyl]-disulfide (BTEPDS) were added to the above mixed solution and mixed evenly. 0.18 mL of 25% ammonia water was added to the system and stirred overnight.

[0027] (3) After the reaction, the nanoparticles were precipitated with 30 mL of acetone and centrifuged at 8000 rpm / min for 5 min. The nanoparticles were washed three times with anhydrous ethanol and ultrapure water to remove the organic reagents on the surface and the unencapsulated proteins attached to the surface of the nanoparticles.

[0028] (4) The nanoparticles prepared in (3) were dispersed in a mixed solution of 50 mL of ethanol and 100 μL of APTES, stirred for 10 h, collected by centrifugation at 8000 rpm for 5 min, and washed three times with anhydrous ethanol and ultrapure water, respectively, to obtain amino-functionalized disulfide-bonded silica (MBS) nanoparticles loaded with MANF protein.

[0029] (5) The nanoparticles prepared in (4) were added to a 15 mg / mL hyaluronic acid aqueous solution and stirred for 0.5 h to obtain silica / hyaluronic acid (MBSH) nanoparticles.

[0030] (6) The nanoparticles in (5) were reacted with 3 mg / mL chitosan solution for 0.5 h to obtain chitosan-modified silica / hyaluronic acid (MBSH@C) nanoparticles loaded with MANF.

[0031] (7) The nanoparticles in (6) were reacted with 1 mg / mL sodium alginate solution for 0.5 h to obtain MANF-loaded sodium alginate and chitosan double-layer coated silica / hyaluronic acid (MBSH@CA) nanoparticles.

[0032] The morphology of the silicon nanoparticles prepared in Example 1 was observed by transmission electron microscopy (TEM). Figure 2 AC shows that the results show that it has a regular spherical surface and good dispersion. The results of dynamic light scattering instrument test show that the average particle size of MBS is 76.45±7.91nm, the potential is +31.99±1.03mV, the average particle size of MBSH is 92.89±5.60nm, the potential is -56.08±3.18mV, the potential of MBSH@C is +48.15±1.91mV, and the particle size of MBSH@CA is 135.85±14.50nm, the potential is -34.6±0.58mV( Figure 2 D).

[0033] Comparative Example 1:

[0034] Preparation of sodium alginate / chitosan double-layer coated hyaluronic acid modified silica nanoparticles (BSH@CA): The difference from Example 1 is that no MANF protein solution is added in step (2).

[0035] Comparative Example 2:

[0036] Preparation of MANF-loaded sodium alginate / chitosan double-layer coated silica nanoparticles (MBS@CA). The difference from Example 1 is that the hyaluronic acid coating step (5) is omitted.

[0037] Comparative Example 3:

[0038] Preparation of sodium alginate / chitosan double-layer coated silica nanoparticles (BS@CA): The difference from Example 1 is that no MANF protein solution is added in step (2) and the hyaluronic acid coating treatment in step (5) is not performed.

[0039] Example 2:

[0040] Biodegradability experiments of oral colon-targeted silica nanomedicines.

[0041] An appropriate amount of MBSH@CA nanomedicine was placed in a buffer solution containing 0mM, 0.1mM and 5mM GSH and incubated. The amount of protein released at different time points was measured to investigate the degradation behavior of the nanomedicine under GSH in the organism.

[0042] The results are as follows Figure 3As shown in Figure A, in the presence of 5 mM GSH, MBSH@CA nanocapsules released 93.27% of the protein after 72 hours. When the GSH concentration was reduced to 0.1 mM, protein release remained above 66.75% after 72 hours. The release of MANF protein in the absence of GSH was approximately 3.26%, demonstrating that this nanomedicine exhibits GSH-responsive properties and can be degraded and released by GSH in vivo.

[0043] Example 3:

[0044] In vitro release experiment of oral colon-targeted silica nanomedicine:

[0045] The silicon nano-hydrogel composite material prepared after FITC labeling MANF was subjected to a simulated gastrointestinal release experiment. It was placed in artificial gastric juice for 2 hours, artificial small intestinal juice for 6 hours, and artificial colonic juice for 52 hours. The supernatant was taken every 1 hour from the gastric juice and small intestinal juice, and every 12 hours from the colonic juice to measure the release amount.

[0046] The results of the protein release experiment in the simulated gastrointestinal tract are as follows Figure 3 As shown in Figure B, the MANF protein in the MBSH@CA nanoparticles is barely released in gastric fluid, but is released in small amounts in small intestinal fluid. However, the total MANF release in simulated small intestinal fluid after 6 hours is still less than 5%, demonstrating good stability. In contrast, MBSH nanoparticles without chitosan and sodium alginate modification show a cumulative release of approximately 15% in simulated small intestinal fluid, indicating that the outer chitosan and alginate layers effectively delay MANF release in the upper gastrointestinal tract. Subsequently, when the release medium was replaced with simulated colonic fluid, the release rate of MANF increased, reaching approximately 80% within 60 hours.

[0047] Example 4:

[0048] Targeting evaluation of oral colon-targeted silica nanomedicines.

[0049] The anthocyanin fluorescent dye Cy 5 was conjugated to silica particles in the silicon nanomedicine. Healthy mice and mice with colitis were then orally administered with the same dose of PBS, Cy 5, BS@CA, BSH@CA, MBS@CA, or MBSH@CA nanoparticles (0.5 mg Cy 5 / kg). Fluorescence in the abdomen of the mice was recorded using an optical imaging system at 2, 6, 12, and 24 hours. Fluorescence imaging of the heart, liver, spleen, lungs, kidneys, and colon was performed 24 hours after administration.

[0050] The results are as follows Figure 4As shown, the fluorescence intensity of the Cy5, BS@CA, and MBS@CA groups gradually weakened over time. The free Cy5 group showed almost no fluorescence after 24 hours, while the fluorescence intensity of the hyaluronic acid (HA)-modified BSH@CA and MBSH@CA groups remained high. After 24 hours, the major organs and gastrointestinal tract of each group were collected for ex vivo fluorescence imaging. The results showed that no fluorescence was observed in the heart, liver, lung, spleen, and kidney in both healthy and colitis mice. Bright fluorescence was only observed in the gastrointestinal tissues, suggesting that MBSH@CA nanoparticles were not distributed to organs other than the colon after oral administration. Ex vivo imaging of gastrointestinal tissues revealed significant accumulation of HA-modified BSH@CA and MBSH@CA groups in the colon. Furthermore, the fluorescence of MBSH@CA-treated colitis mice was stronger than that of healthy mice. These results indicate that HA plays an important role in enhancing the targeting ability of MBSH@CA to the inflamed colon.

[0051] Example 5:

[0052] Biocompatibility evaluation of oral colon-targeted silica nanomedicines.

[0053] In vivo biocompatibility experiments were conducted in 30 female C57BL / 6 mice divided into five groups and orally administered with PBS, BS@CA, BSH@CA, MBS@CA, or MBSH@CA nanoparticles. The MBS@CA or MBSH@CA groups received a dose of 15 mg / kg of MANF, while the BS@CA and BSH@CA groups received 500 mg / kg once daily for seven consecutive days. The mice were fasted for 24 hours before being sacrificed. Daily body weights were recorded during the dosing period. Blood samples were collected for routine blood analysis after sacrifice, and major organ and gastrointestinal tissues (heart, liver, spleen, lung, kidney, colon, stomach, small intestine, large intestine, duodenum, and cecum) were collected for hematoxylin-eosin staining.

[0054] The results are as follows Figure 5 The results showed that there was no significant difference in the body weight between the experimental groups and the control group ( Figure 5 A), all blood routine indicators were within the normal range, and there was no significant difference between the experimental groups and the control group ( Figure 5 B), Hematoxylin-eosin staining results ( Figure 5 C) showed that the BS@CA, BSH@CA, MBS@CA, and MBSH@CA nanoparticle groups did not cause pathological changes and inflammatory lesions in the organs and digestive system of mice compared with the control group.

[0055] Example 6:

[0056] Evaluation of the efficacy of MANF oral colon-targeted delivery system in ulcerative colitis.

[0057] Forty-two female C57BL / 6 mice were divided into seven groups. Mice in the ulcerative colitis model (DSS dextran sulfate sodium model) were allowed to drink freely for seven days. From the third to eighth day, they were orally gavaged with PBS, BS@CA, BSH@CA, MBS@CA, MBSH@CA nanoparticles, or 5-aminosalicylic acid (5-ASA). Healthy mice served as controls. The MBS@CA and MBSH@CA groups received a MANF dose of 3 mg / kg. The BS@CA and BSH@CA groups maintained the same silica dose as the MBS@CA and MBSH@CA groups, with a 5-ASA dose of 20 mg / kg. 5-ASA is a commonly used oral medication for ulcerative colitis. The oral administration of MBSH@CA in the present invention is effective in treating ulcerative colitis at a lower dose (3 mg / kg) than 5-ASA (20 mg / kg). During treatment, body weight, rectal bleeding, and stool consistency were checked daily, and the Disease Activity Index (DAI) was determined: percentage of weight loss (0-4), stool consistency index (0-4), and rectal blood index (0-4). Mice were sacrificed after a one-day fast, and spleen and colon were collected. Spleen weight and colon length were recorded. Colon tissue was histologically sectioned, and orbital blood was collected to measure serum inflammatory cytokine levels.

[0058] Weight results as Figure 6 As shown in Figure B, the weight of mice in the DSS model group gradually decreased compared with the healthy control group, and decreased by about 20% on the eighth day. Compared with the PBS group, the weight of mice in the oral gavage BS@CA and BSH@CA groups was on a downward trend. However, after oral administration of MBS@CA and MBSH@CA nanoparticles, the weight of mice showed an upward trend on the seventh day, and the weight increase trend of mice in the MBSH@CA group was the most obvious. Consistent with the weight change results, the disease activity index ( Figure 6 C), colon length ( Figure 6 D, 6F) and spleen index ( Figure 6 E, 6F) also showed that MBSH@CA nanocapsules had the best therapeutic effect. HE staining results ( Figure 6 G) shows that the colon of mice in the DSS group showed obvious immune cell infiltration, mucosal tissue loss, and disappearance of goblet cells and crypt structures, while the crypt structure in the MBSH@CA group was partially restored and tissue damage was alleviated. The analysis results of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α and MPO levels in the serum of mice in each experimental group are shown in Figure 2. Figure 7 As shown in the results, MBSH@CA treatment significantly reduced the levels of IL-6, IL-1β, TNF-α, and MPO in colitis mice, indicating that MBSH@CA can alleviate colitis by regulating the levels of MPO, IL-6, IL-1β, and TNF-α.

[0059] It should be noted that the technical contents of the present invention described above are only for the purpose of explaining and illustrating the technical essence of the present invention to enable those skilled in the art to understand the technical essence of the present invention. Therefore, the technical contents described above are not intended to limit the substantial protection scope of the present invention. The substantial protection scope of the present invention shall be based on the claims. Those skilled in the art should be aware that any modifications, equivalent substitutions, and improvements based on the substantial spirit of the present invention shall fall within the substantial protection scope of the present invention.

Claims

1. An oral colon-targeted silica nanomedicine comprising silica nanoparticles loaded with MANF, hyaluronic acid coated on the silica nanoparticles, and a chitosan / sodium alginate double-layer coating coated on the hyaluronic acid; the MANF-loaded silica nanoparticles are amino-functionalized silica nanoparticles with disulfide bonds.

2. The oral colon-targeted silicon nanomedicine according to claim 1, characterized in that: The amino-functionalized silicon nanoparticles with disulfide bonds are prepared by uniformly mixing cyclohexane, n-hexanol, and Triton X-100, then adding a 1-10 mg / mL MANF protein solution, TEOS, and BTEPDS, and mixing them uniformly. Ammonia water with a concentration of 20%-30% is then added and stirred overnight. The nanoparticles are precipitated using acetone, and the nanoparticles are dispersed in a mixed solution of ethanol and APTES, and stirred for 6-15 hours.

3. The oral colon-targeted silicon nanomedicine according to claim 2, characterized in that: The volume ratio of cyclohexane, n-hexanol and Triton X-100 is 20-25:5-6:5-6.

4. The oral colon-targeted silicon nanomedicine according to claim 2, characterized in that: The concentration of the MANF protein solution is 1-5 mg / mL.

5. The oral colon-targeted silicon nanomedicine according to claim 2, characterized in that: The volume ratio of the MANF protein solution, TEOS, and BTEPDS is 5-15:2-3:2-3.

6. The oral colon-targeted silicon nanomedicine according to claim 2, characterized in that: The volume ratio of ethanol to APTES is 300-600:

1.

7. The oral colon-targeted silicon nanomedicine according to claim 2, characterized in that: The preparation method of the amino-functionalized silicon nanoparticles with disulfide bonds is as follows: 20-25 mL of cyclohexane, 5-6 mL of n-hexanol and 5-6 mL of Triton X-100 are mixed uniformly and stirred for 0.5-1 hour. Then, 0.5-1.5 mL of a 1-10 mg / mL MANF protein solution, 0.2-0.3 mL of TEOS and 0.2-0.3 mL of BTEPDS are added to the mixed solution and mixed uniformly. 0.16-0.20 mL of 20-30% ammonia water is added to the system and stirred overnight. After the reaction is completed, the nanoparticles are precipitated with 20-50 mL of acetone. Finally, the prepared nanoparticles are dispersed in a mixed solution of 30-60 mL of ethanol and 100 μL of APTES, stirred and centrifuged for collection.

8. Use of the oral colon-targeted silicon nanomedicine according to any one of claims 1 to 7 in the preparation of a pharmaceutical preparation for treating ulcerative colitis.

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