Use of aldisin compounds for the preparation of a medicament for the treatment of inflammatory bowel disease

Abstract

The application discloses application of an Aldisin compound or a pharmaceutical salt thereof in preparation of a medicine for treating inflammatory bowel disease, and a structure of the Aldisin compound is as shown in the following formula: The Aldisin compound has a significant therapeutic effect on inflammatory bowel disease as a small molecule compound, has the characteristics of low toxicity and significant curative effect, and thus can be used as a leading compound for the major disease of inflammatory bowel disease, has important development prospect and clinical application value, and also provides a scientific basis for further exploration of a mechanism of IBD.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically, it relates to the application of an Aldisin compound in the preparation of a drug for treating inflammatory bowel disease. Background Technology

[0002] Inflammatory bowel disease (IBD) is a group of specific autoimmune reactions caused by a variety of factors, including genetics, immunity, infection, environment, and diet. It includes ulcerative colitis (UC) and Crohn's disease (CD), and its main clinical manifestations are diarrhea, hematochezia, and weight loss. The pathogenesis of IBD is not fully understood, but it is currently believed to be related to genetics, environment, and immunity.

[0003] Currently, there are five classes of commonly used drugs for treating IBD: aminosalicylates, glucocorticoids, immunosuppressants, antibiotics, and biologics. In conventional treatment, aminosalicylates are used only for the active phase and maintenance therapy of mild to moderate IBD; glucocorticoids and immunosuppressants are used for the active phase and maintenance therapy of moderate to severe IBD; and biologics are usually used for patients who do not respond to hormones and immunosuppressants. From a safety perspective, existing IBD treatments can cause a range of adverse reactions, including infections, tumors, hematologic disorders, and autoimmune disorders. In terms of efficacy, while conventional treatments can improve symptoms, they have a high relapse rate and are not very effective for severely ill patients. For biologics, such as anti-TNF-α, approximately 30% of users do not respond, and among responders, approximately 10% fail to respond annually. With advancements in technology, the emergence of various novel biologics has provided new options for IBD treatment, such as adhesion factor inhibitors, S1P receptor modulators, Janus kinase inhibitors, and MAPK inhibitors; however, their safety and efficacy still require further evaluation through larger-scale clinical trials. Overall, the clinical remission rate of current IBD treatments does not exceed 50%. Therefore, developing novel small molecule drugs with fewer side effects, clear targets, and significant therapeutic effects remains an important direction for the development of innovative drugs for IBD.

[0004] It is currently believed that intestinal barrier dysfunction is closely related to the onset and progression of IBD. Damage to the intestinal barrier can allow harmful substances to enter the intestinal wall tissue through the intestinal mucosa, activating the immune system and triggering an inflammatory response. This inflammatory response may be due to increased intestinal barrier permeability, allowing bacteria, toxins, and other harmful substances to cross the intestinal mucosa, leading to intestinal flora imbalance and stimulating immune cells to release inflammatory factors, thereby triggering intestinal inflammation. Therefore, maintaining the integrity of the intestinal barrier function is crucial for the prevention and treatment of inflammatory bowel disease.

[0005] Oxidative stress plays a crucial role in maintaining intestinal barrier function. Its effects are multifaceted, directly damaging intestinal epithelial cells and potentially impacting the function of the mucus layer and immune system, as well as the balance of the gut microbiota, thereby increasing the risk of inflammatory bowel disease (IBD). Therefore, reducing oxidative stress and protecting the integrity of the intestinal barrier function are of great significance for the prevention and treatment of IBD. Summary of the Invention

[0006] The purpose of this invention is to provide the use of the Aldisin compound in the preparation of a medicament for treating inflammatory bowel disease.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] In a first aspect, the present invention provides the use of an Aldisin compound or a pharmaceutical salt thereof in the preparation of a medicament for treating inflammatory bowel disease.

[0009] The structure of the Aldisin compound (Xiong S, Pang HD, Fan J, Ge F, et al. In vitro and invivo antineoplastic activity of a novel bromopyrrole and its potential mechanism of action. Br J Pharmacol. 2010 Feb; 159(4):909-18.) is shown below:

[0010]

[0011] Dextran sodium sulfate (DSS)-induced models are a commonly used tool in the study of colitis (UC). Adding a certain concentration of DSS to the drinking water induces colitis in mice. DSS can damage colonic epithelial cells, impairing the epithelial barrier function, thus allowing inflammatory substances to penetrate into the lamina propria and submucosa, triggering an abnormal immune response. This leads to weight loss, bleeding, diarrhea, and bloody stools in mice, mimicking UC symptoms. Aldisin compounds can effectively improve UC symptoms, reduce diarrhea and bloody stools in mice, slow weight loss and colonic shortening, reduce inflammatory cell infiltration, decrease intestinal damage, and have a significant protective effect on the epithelial mucosal barrier.

[0012] The dosage of the Aldisin compound is 40 mg / kg.

[0013] The medicine for treating inflammatory bowel disease is an Aldisin compound as the sole active ingredient, or an Aldisin compound and at least one pharmaceutically permissible excipient forming a pharmaceutical composition.

[0014] The Aldisin compound can be formulated into pharmaceutical preparations.

[0015] The dosage form of the pharmaceutical preparation is selected from liquid preparations, tablets, or capsules.

[0016] The drug preparation can be administered orally, intravenously, intraperitoneally, or via enema.

[0017] This invention demonstrates through both whole-animal and cellular experiments that the compound Aldisin can effectively treat inflammatory bowel disease (IBD), specifically as follows: Animal experiments show that Aldisin has a significant therapeutic effect on a DSS-induced IBD model, effectively slowing down weight loss and colon shortening in mice; it effectively reduces inflammatory cell infiltration, decreases intestinal damage, and has a significant protective effect on the epithelial mucosal barrier, increasing goblet cell expression and promoting the expression of goblet cell tight junction protein genes; it also significantly inhibits the release of inflammatory factors TNF-α and IL-6 from serum and the intestine, thereby alleviating or slowing the course of IBD; Aldisin has no significant effect on the liver, lungs, kidneys, or other organs in mice, indicating that the compound has no significant toxicity. Cellular experiments show that Aldisin protects intestinal epithelial cells by restoring the reduction in intracellular tight junction proteins caused by IFNγ / LPS stimulation and inhibiting the production of the inflammatory factor IL-8. These results demonstrate that Aldisin can indeed effectively treat IBD and can therefore be used to prepare drugs for treating IBD or other inflammatory immune diseases.

[0018] By adopting the above technical solution, the present invention has the following advantages and beneficial effects:

[0019] The Aldisin compound of this invention, as a small molecule compound, exhibits significant therapeutic effects on inflammatory bowel disease (IBD), characterized by low toxicity and remarkable efficacy. Therefore, the Aldisin compound can serve as a lead compound for this major disease, possessing significant development potential and clinical application value. It also provides a scientific basis for further exploring the pathogenesis of IBD. Attached Figure Description

[0020] Figure 1 This is a schematic diagram illustrating how the Aldisin compound slows down the weight loss in mice with DSS-induced IBD.

[0021] Figure 2This is a schematic diagram illustrating the inhibition of DSS-induced IBD in mice by the Aldisin compound.

[0022] Figure 3 This is a schematic diagram illustrating how the Aldisin compound improves intestinal barrier function in mice with DSS-induced IBD.

[0023] Figure 4 This is a schematic diagram illustrating the inhibition of inflammatory factor release in mice with DSS-induced IBD by the Aldisin compound.

[0024] Figure 5 This is a schematic diagram illustrating the inhibition of DSS-induced IBD in mouse colonic oxidative stress by the Aldisin compound.

[0025] Figure 6 This is a schematic diagram of the Nrf2 / HO-1 signaling pathway in the colon of IBD mice activated by the Aldisin compound and DSS-induced.

[0026] Figure 7 This is a schematic diagram showing that the Aldisin compound has no significant toxicity to any organ in mice with DSS-induced IBD.

[0027] Figure 8 This is a schematic diagram showing that Aldisin has no significant toxicity to HT-29 human colon cancer cells.

[0028] Figure 9 This is a schematic diagram illustrating how the Aldisin compound inhibits the release of IL-8 from IFNγ / LPS-stimulated HT-29 human colon cancer cells.

[0029] Figure 10 This is a schematic diagram illustrating how the Aldisin compound restores the reduction of tight junction proteins in IFNγ / LPS-stimulated HT-29 human colon cancer cells. Detailed Implementation

[0030] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0031] Example 1

[0032] Effects of Aldisin compounds on DSS-induced IBD models

[0033] Materials: C57BL / 6 was purchased from Shengchang Biotechnology Co., Ltd.; sodium dextran sulfate was purchased from MP Biotechnology Co., Ltd. (USA); mouse inflammation cytometric bead array assay was purchased from R&D Systems; antibodies Nrf2, NQO1, HO-1, and β-actin were all purchased from Cell Signal Technology; MPO detection kit, SOD detection kit, and MDA detection kit were all purchased from Nanjing Jiancheng Biotechnology Institute.

[0034] Experimental methods:

[0035] 1. Establishment of a dextran sulfate sodium (DSS)-induced IBD model: Based on The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T cells in Ulcerative Colitis. J Crohns Colitis. 2020. 14(4): 508-524 and Hepatic cytochrome P4508B1 and cholic acid potentiate intestinal epithelial injury incolitis by suppressing intestinal stem cell renewal. Cell Stem Cell. 202229(9): 1366-1381, 50 male C57BL / 6 mice were randomly divided into 6 groups: control group (NC group), 2.5% DSS group, and 250mg / kg group. Eight mice were assigned to each of the following groups: 5-aminosalicylic acid (5-ASA) group, low-dose Aldisin group (10 mg / kg), medium-dose Aldisin group (20 mg / kg), and high-dose Aldisin group (40 mg / kg). Mice were allowed free access to 2.5% DSS solution for 7 days (modeling period) and normal drinking water for 3 days (recovery period). Starting from the first day of modeling, mice were intraperitoneally injected daily with 10 mg / kg Aldisin, 20 mg / kg Aldisin, and 40 mg / kg Aldisin, respectively, and administered 5-aminosalicylic acid by gavage. Mouse weight was measured daily, and fecal characteristics and bleeding were recorded.

[0036] 2. Relevant indicators after establishing the IBD model: On day 10 after modeling, mice were sacrificed, blood was collected from the orbital cavity, and the release of inflammatory factors TNFα and IL-6 in serum was detected; liver, kidney, lung, and spleen tissue specimens were isolated, and histopathological changes were analyzed using hematoxylin-eosin staining; mouse colon tissue was isolated, the length of the mouse colon was measured, and the number of goblet cells in the intestine was analyzed using Alcian blue-Periodic Acid-Schiffstain (AB-PAS staining method); the expression of inflammatory factors TNFα, IL-6, IL-1β and related transcription factors in the mouse intestine was detected by RT-PCR.

[0037] The results show:

[0038] 1. The effect of compound Aldisin on body weight in DSS-induced IBD mice is as follows: Figure 1 As shown, Figure 1 This diagram illustrates how the Aldisin compound slows down the weight loss in mice with DSS-induced IBD. After DSS induction, compared to the NC group, the DSS model group showed a significant decrease in body weight. Both the Aldisin and 5-ASA groups effectively slowed down this weight loss, with the Aldisin (20 mg / kg) group showing the most significant effect (p<0.001). This indicates that Aldisin can effectively slow down the weight loss in DSS-induced IBD mice.

[0039] 2. The effect of compound Aldisin on colon length in DSS-induced IBD mice is as follows: Figure 2 As shown, Figure 2 This is a schematic diagram illustrating the inhibition of colonic shortening in DSS-induced IBD mice by the compound Aldisin. After DSS induction, compared to the NC group, the colonic length of the model group mice was significantly shortened. The Aldisin and 5-ASA groups effectively inhibited this shortening, indicating that Aldisin can effectively inhibit DSS-induced colonic shortening in IBD mice.

[0040] 3. The results of the compound Aldisin improving intestinal barrier function in DSS-induced IBD mice are as follows: Figure 3 As shown, Figure 3 This is a schematic diagram illustrating how the Aldisin compound improves intestinal barrier function in mice with DSS-induced IBD. Figure 3In the middle, C, D, E, and F, the bars from left to right are NC, 2.5% DSS, 2.5% DSS + Aldisin (10 mg / kg), 2.5% DSS + Aldisin (20 mg / kg), 2.5% DSS + Aldisin (40 mg / kg), and 2.5% DSS + 5-ASA (250 mg / kg). HE staining analysis showed that compared to the NC group, the 2.5% DSS group showed significant inflammatory infiltration and congestion in the colon tissue of mice. The 5-ASA and Aldisin groups significantly improved the pathological changes induced by DSS in IBD mice, reducing the degree of inflammatory infiltration and maintaining relatively intact tissue structure. Figure 3 (As shown in Figure A); The presence of goblet cells secreting mucin in the colonic epithelium was analyzed using AB-PAS staining and Alcian blue staining. The results showed that the mucus layer in the model group was thinner, mature goblet cells were severely lost, goblet cells in each crypt were significantly reduced, and the mucus layer was significantly damaged. Mice in the Aldisin and 5-ASA groups reversed the reduction in goblet cells after 2.5% DSS stimulation and both promoted mucin secretion. The medium and high doses of Aldisin showed a more significant protective effect on the intestinal barrier. Figure 3 (As shown in Figure B); Simultaneously, RT-PCR was used to detect the expression of goblet cell-specific gene MUC2, as well as mucus secretion-related genes such as trefoil factor TFF3, and key transcription factors SPDEF and KLF4, which govern goblet cell differentiation. The results showed that in the colon tissue of the DSS model group, the expression of MUC2, TFF3, SPDEF, and KLF4 genes was significantly reduced, while the expression of these genes was significantly increased in the Aldisin and 5-ASA groups. Figure 3 (As shown in CF). The results indicate that the compound Aldisin effectively improves the damage to the intestinal barrier function caused by DSS in mice.

[0041] 4. The results of the compound Aldisin inhibiting the release of inflammatory factors in DSS-induced IBD mice are as follows: Figure 4 As shown, Figure 4This diagram illustrates how the compound Aldisin inhibits the release of inflammatory factors in mice with DSS-induced IBD. The bars, from left to right, represent NC, 2.5% DSS, 2.5% DSS + 5-ASA (250 mg / kg), 2.5% DSS + Aldisin (10 mg / kg), 2.5% DSS + Aldisin (20 mg / kg), and 2.5% DSS + Aldisin (40 mg / kg). Ten days after DSS modeling, blood was collected from the orbital sinus, and the levels of TNFα and IL-6 in mouse serum were detected using ELISA. The results showed that compared with the NC group, the levels of pro-inflammatory mediators TNFα and IL-6 in the serum of the 2.5% DSS group were significantly increased. Both Aldisin and 5-ASA effectively reduced the levels of TNFα and IL-6. Figure 4 As shown in Figure A), similarly, RNA was extracted from the mouse colon, and the expression of inflammatory mediators TNFα and IL-6 in the mouse colon was detected by RT-PCR. The results showed that the compound Aldisin significantly reduced the expression of TNFα and IL-6 compared to the 2.5% DSS group. Figure 4 (As shown in Figure B). The results indicate that the compound Aldisin can effectively reduce the levels of inflammatory TNFα and IL-6 in DSS-induced IBD mice, thereby inhibiting the inflammatory response.

[0042] 5. The compound Aldisin inhibited DSS-induced oxidative stress in the colon of IBD mice. Figure 5 As shown, Figure 5 This is a schematic diagram illustrating the inhibition of DSS-induced IBD by the compound Aldisin in mouse colonic oxidative stress. In the diagram, the bars from left to right represent NC, 2.5% DSS, 2.5% DSS + 5-ASA (250 mg / kg), 2.5% DSS + Aldisin (10 mg / kg), 2.5% DSS + Aldisin (20 mg / kg), and 2.5% DSS + Aldisin (40 mg / kg). Oxidative stress mainly occurs during inflammatory responses, where inflammatory cells produce large amounts of reactive oxygen species (ROS). ROS damage cell membranes and reduce the levels of antioxidant enzymes such as SOD and GSH-Px. Therefore, CAT, SOD, and GSH-Px are often used as important indicators of oxidative stress responses. Compared with the control group, the levels of SOD, CAT, and GSH-Px in the colonic tissue of the 2.5% DSS group were significantly decreased. Figure 5 As shown in AC), the level of MDA was significantly increased ( Figure 5 (As shown in D). Compared with the DSS group, the Aldisin group and the 5-ASA group showed significantly increased SOD activity, CAT activity, and GSH content in colon tissue, and significantly decreased MDA content. Figure 5 (As shown in AD).

[0043] 6. Results of Aldisin activating the Nrf2 / HO-1 signaling pathway in the colon of IBD mice induced by DSS are as follows: Figure 6 As shown, Figure 6 This diagram illustrates the activation of the Nrf2 / HO-1 signaling pathway in the colon of DSS-induced IBD mice by the compound Aldisin. Western blot analysis revealed a significant decrease in the expression of Nrf2, NQO1, and HO-1 in the colonic tissue of the DSS model group compared to the control group, indicating a significant inhibition of antioxidant signaling pathways in the model group mice. Figure 6 As shown in AD), the expression of Nrf2, NQO1, and HO-1 proteins in the colon tissue of the Aldisin and 5-ASA groups was significantly increased. Figure 6 (As shown in AD). Similarly, RT-PCR analysis revealed that, compared with normal mice, the expression levels of Nrf2, HO-1, and NQO1 mRNA in the colon tissue of the model group were significantly reduced (as shown in AD). Figure 6 As shown in the EG diagram, the expression levels of Nrf2, HO-1, and NQO1 genes in the colon tissue of mice in the Aldisin and 5-ASA groups were significantly increased. Figure 6 (As shown in the EG diagram). This indicates that Aldisin can reduce cell damage and achieve the goal of treating IBD by activating the Nrf2 / HO-1 signaling pathway and inhibiting oxidative stress.

[0044] 7. The compound Aldisin showed no significant toxicity to any organ in DSS-induced IBD mice. Figure 7 As shown, Figure 7 This diagram illustrates that the compound Aldisin showed no significant toxicity to any organ in mice with DSS-induced IBD. HE staining also confirmed that Aldisin caused no significant damage to organs such as the liver, kidneys, lungs, and spleen.

[0045] Aldisin, as a small molecule compound, has low toxicity and no significant toxicity to the lungs, liver, or kidneys. In vivo experiments have confirmed that Aldisin effectively protects the intestinal mucosa, reduces damage to the intestines from inflammatory factors, avoids colonic shortening caused by DSS stimulation, and slows down weight loss by activating the Nrf2 / HO-1 signaling pathway. It has a significant therapeutic effect on inflammatory bowel disease.

[0046] Example 2

[0047] Effects of Aldisin compounds on inflammatory factors and tight junction proteins produced in human colon cancer cells HT-29 stimulated by LPS / IFNγ.

[0048] Materials: Human colon cancer cells HT-29 were purchased from the Cell Bank of the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; LPS was purchased from Sigma; IFNγ was purchased from MCE; CCK8 reagent was purchased from Tongren Chemical; ELISA MAX TM Standard Set Human IL-8 was purchased from Biolegend; antibodies Claudin-1, Occludin, and Claudin-4 were all purchased from Cell Signal Technology.

[0049] Experimental methods:

[0050] 1. Detection of the effect of Aldisin compound on the activity of HT-29 human colon cancer cells: HT-29 cells were divided into groups of 5*10... 3 Cells / ml were seeded into 96-well plates and incubated overnight. Different concentrations of the compound Aldisin (0, 1, 5, 10, 20, 40, and 80 μM) were added. After 24 hours, the effect of the compound Aldisin on cell growth was detected by CCK8 assay.

[0051] 2. Detection of the effect of Aldisin compound on IFNγ / LPS-stimulated inflammatory factors in human colon cancer cells HT-29: RAW264.7 cells were divided into groups of 5*10... 5 Cells / ml were seeded in 12-well plates and incubated overnight. Different concentrations of Aldisin compound (doses of 1, 5, 10, 20, and 40 μM) were added. After culturing for 2 hours, IFNγ 20 ng / ml was added for stimulation for 12 hours, followed by LPS 100 ng / ml for another 12 hours. The effect of Aldisin compound on the inflammatory factor IL-8 of IFNγ / LPS stimulation of HT-29 cells was detected by ELISA.

[0052] 3. Detection of the effect of Aldisin compound on tight junction proteins in IFNγ / LPS-stimulated HT-29 cells: HT-29 cells were divided into groups of 1*102 6 Cells / ml were seeded in 6-well plates and incubated overnight. Different concentrations of Aldisin compound (10, 20, and 40 μM) were added and cultured for 2 hours. Then, IFNγ 20 ng / ml was added for stimulation for 12 hours, followed by LPS 100 ng / ml for another 12 hours. Proteins were extracted and the expression of tight junction proteins in cells was detected by Western blot.

[0053] The results show:

[0054] 1. The effect of Aldisin compound on the activity of HT-29 human colon cancer cells is as follows: Figure 8 As shown, Figure 8This is a schematic diagram illustrating the lack of significant toxicity of Aldisin to HT-29 human colon cancer cells. CCK8 assay revealed that the Aldisin compound had no significant toxicity to HT-29 human colon cancer cells.

[0055] 2. The effect of Aldisin compound on the release of inflammatory factor IL-8 from IFNγ / LPS-stimulated HT-29 human colon cancer cells is as follows: Figure 9 As shown, Figure 9 This diagram illustrates how the Aldisin compound inhibits the release of IL-8 from IFNγ / LPS-stimulated HT-29 human colon cancer cells. IL-8, also known as the chemokine CXCL8, is a pro-inflammatory cytokine secreted by epithelial cells. IL-8 exerts chemotactic activity on neutrophils by binding to chemokine receptors CXCR1 and CXCR2, thereby regulating the inflammatory response. Twenty-four hours after IFNγ / LPS stimulation, HT-29 cells release a large amount of the inflammatory cytokine IL-8, while the Aldisin compound dose-dependently reduces the release of this inflammatory cytokine. This indicates that the Aldisin compound possesses significant anti-inflammatory activity and can effectively inhibit the increased expression of IL-8 caused by IFNγ / LPS stimulation.

[0056] 3. The effect of Aldisin compound on tight junction proteins in IFNγ / LPS-stimulated HT-29 human colon cancer cells, the results are as follows: Figure 10 As shown, Figure 10 This diagram illustrates how the Aldisin compound restored the reduction in tight junction proteins in HT-29 human colon cancer cells stimulated by IFNγ / LPS. Western blot analysis confirmed that stimulation of HT-29 cells with 20 ng / mL IFN-γ and 100 ng / mL LPS significantly decreased the expression levels of Claudin-1, Claudin-4, and Occludin proteins, while the Aldisin compound significantly increased the expression levels of tight junction proteins in HT-29 cells. Figure 10 (As shown in AD). Similarly, RT-PCR analysis revealed that IFNγ / LPS stimulation significantly reduced the expression levels of Claudin-1, Occludin, and Claudin-4 in cells; while the Aldisin compound was able to restore the gene expression of Claudin-1, Occludin, and Claudin-4 that was reduced by IFNγ / LPS stimulation. Figure 10 (As shown in EG). This indicates that the Aldisin compound alleviates intercellular connection damage under inflammatory conditions.

[0057] In vitro experiments have confirmed that Aldisin can protect intestinal mucosal cells by inhibiting the release of the inflammatory factor IL-8 and the expression of tight junction proteins.

[0058] The Aldisin compound of this invention can effectively treat inflammatory bowel disease (IBD) in mice, slowing down weight loss; inhibiting colonic shortening; improving intestinal barrier function in IBD mice, reducing the degree of intestinal inflammatory infiltration, inhibiting the reduction of goblet cell numbers, promoting the secretion of tight junction proteins by goblet cells, and maintaining the relative integrity of tissue structure; by activating the Nrf2 / HO-1 signaling pathway, it alleviates intestinal damage caused by oxidative stress, thereby effectively reducing the levels of inflammatory TNFα and IL-6 in IBD mice, thus alleviating or slowing down the pathogenesis of IBD; and it has no significant toxicity to any organ in DSS-induced IBD mice. In in vitro experiments, IFNγ / LPS stimulation of HT-29 cells confirmed that the Aldisin compound protects intestinal epithelial cells by restoring the expression of intracellular tight junction proteins and inhibiting the production of the inflammatory factor IL-8.

[0059] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. The use of an Aldisin compound or a pharmaceutical salt thereof in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The structure of the Aldisin compound is shown below:

2. The use of the Aldisin compound or its pharmaceutical salt according to claim 1 in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The dosage of the Aldisin compound is 40 mg / kg.

3. The use of the Aldisin compound or its pharmaceutical salt according to claim 1 in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The medicine for treating inflammatory bowel disease is an Aldisin compound as the sole active ingredient, or an Aldisin compound and at least one pharmaceutically permissible excipient forming a pharmaceutical composition.

4. The use of the Aldisin compound or its pharmaceutical salt according to claim 1 in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The Aldisin compound was formulated into a pharmaceutical preparation.

5. The use of the Aldisin compound or its pharmaceutical salt according to claim 4 in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The dosage form of the pharmaceutical preparation is selected from liquid preparations, tablets, or capsules.

6. The use of the Aldisin compound or its pharmaceutical salt according to claim 4 in the preparation of a medicament for treating inflammatory bowel disease, characterized in that, The drug preparation can be administered orally, intravenously, intraperitoneally, or via enema.

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