Application of palmitoylcarnitine in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease

Abstract

This invention relates to the field of biomedicine, specifically the application of palmitoylcarnitine in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease. Palmitoylcarnitine has low preparation costs and no obvious toxic side effects. It can comprehensively improve colitis symptoms by increasing the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes and reducing the levels of pro-inflammatory factors such as IL17 and IFNγ, and can be used in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to the use of palmitoylcarnitine in the preparation of medicaments for the prevention and / or treatment of inflammatory bowel disease. Background Technology

[0002] Palmitoylcarnitine belongs to the acylcarnitine class of organic compounds and is a fatty acid lipid molecule. As an important intermediate in the mitochondrial fatty acid oxidation process, palmitoylcarnitine can promote fatty acid oxidation metabolism, improve the body's energy utilization, and reduce body fat accumulation. In addition, palmitoylcarnitine can also promote muscle growth and repair, and improve the body's athletic ability and endurance.

[0003] Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory bowel disease, primarily including ulcerative colitis and Crohn's disease. Ulcerative colitis, in particular, is a chronic inflammatory disease with an unclear etiology, but it may be related to multiple factors such as genetics, immunity, and infection. Currently, the main medications used clinically to treat IBD include salicylates, glucocorticoids, and immunosuppressants. These medications are primarily used to reduce inflammation, suppress the immune response, and alleviate symptoms.

[0004] However, there are currently no literature reports on the activity of palmitoylcarnitine in the anti-inflammatory bowel disease and its mechanism of action. Summary of the Invention

[0005] The purpose of this invention is to provide the application of palmitoylcarnitine in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease, aiming to expand the clinical application of palmitoylcarnitine and provide new treatment methods or drugs for the treatment or prevention of inflammatory bowel disease.

[0006] To achieve the above objectives, a first aspect of the present invention provides the use of palmitoylcarnitine in the preparation of medicaments for the prevention and / or treatment of inflammatory bowel disease.

[0007] Furthermore, the inflammatory bowel disease mentioned is ulcerative colitis or Crohn's disease.

[0008] Furthermore, in the aforementioned drugs for the prevention and / or treatment of inflammatory bowel disease, palmitoylcarnitine improves symptoms of colonic shortening, disease activity index, inflammatory cell infiltration, submucosal edema, and crypt cysts caused by colitis; palmitoylcarnitine comprehensively improves colitis symptoms by increasing the proportion of Treg cells in mesenteric lymph nodes and decreasing the proportion of CD4+IL17+T cells and CD4+IFNγ+T cells in mesenteric lymph nodes.

[0009] Furthermore, the aforementioned drug for the prevention and / or treatment of inflammatory bowel disease is a pharmaceutical composition consisting of palmitoylcarnitine as the sole active monomeric component, or palmitoylcarnitine in combination with other drugs.

[0010] Furthermore, the medicament for the prevention and / or treatment of inflammatory bowel disease also includes pharmaceutically acceptable excipients, such as any one or more of the following: diluents, binders, lubricants, disintegrants, emulsifiers, solubilizers, osmotic pressure regulators, surfactants, coating materials, antioxidants, antibacterial agents, and buffers.

[0011] Furthermore, the dosage form of the drug for the prevention and / or treatment of inflammatory bowel disease is any one or more of the following: suspension, granules, capsules, tablets, powders, emulsions, solutions, pellets, injections, suppositories, enemas, aerosols, patches, or drops.

[0012] Furthermore, the route of administration of the drug for the prevention and / or treatment of inflammatory bowel disease is any one or more of the following: oral administration, intravenous administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, sublingual administration, transdermal administration, or rectal suppository administration.

[0013] Furthermore, in the aforementioned medication for the prevention and / or treatment of inflammatory bowel disease, the dosage of palmitoylcarnitine is 4 mg / kg / day.

[0014] In a second aspect, the present invention provides a medicament for the prevention and / or treatment of inflammatory bowel disease, wherein the medicament is composed of palmitoylcarnitine as the sole active monomeric component, or palmitoylcarnitine in combination with other drugs to form a pharmaceutical composition.

[0015] The advantages of this invention are:

[0016] The palmitoylcarnitine involved in this invention has low preparation cost and no obvious toxic side effects. Animal experiments have demonstrated that palmitoylcarnitine can comprehensively improve colitis symptoms by increasing the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes and decreasing the proportion of CD4+IL17+ T cells and CD4+IFNγ+ T cells in mesenteric lymph nodes, and can be used to prepare drugs for the prevention and / or treatment of inflammatory bowel disease. Attached Figure Description

[0017] Figure 1 A schematic diagram of colon length in mice of each group (from left to right: control group, DSS group, DSS+Pal group; the results shown in the figure are mean ± SEM, n=5).

[0018] Figure 2A schematic diagram of disease activity index for mice in each group (the horizontal axis represents the number of treatment days, and the vertical axis represents the disease activity index; * represents the comparison with the control group, and # represents the comparison with the model group; the results shown in the figure are mean ± SEM, n = 5).

[0019] Figure 3 Schematic diagram of HE staining of colon sections from mice in each group (from left to right: control group, DSS group, DSS+Pal group; magnification: 200x).

[0020] Figure 4 A schematic diagram of the proportion of CD4+FOXP3+Treg cells in the mesenteric lymph nodes of mice in each group (from left to right: control group, DSS group, DSS+Pal group; the results shown in the figure are mean ± SEM, n=5).

[0021] Figure 5 A schematic diagram of the proportion of CD4+IL17+T cells in the mesenteric lymph nodes of mice in each group (from left to right: control group, DSS group, DSS+Pal group; the results shown in the figure are mean ± SEM, n=5).

[0022] Figure 6 A schematic diagram of the proportion of CD4+IFNγ+ T cells in the mesenteric lymph nodes of mice in each group (from left to right: control group, DSS group, DSS+Pal group; the results shown in the figure are mean ± SEM, n=5). Detailed Implementation

[0023] The specific implementation methods provided by the present invention will be described in detail below with reference to the embodiments.

[0024] Example:

[0025] 1. Experimental Materials

[0026] Fifteen male C57 / BL6 mice (8 weeks old) were purchased from Shanghai Bikeyi Biotechnology Co., Ltd.

[0027] Palmitoyl carnitine was purchased from Taoshu Biotechnology Co., Ltd. (T37299).

[0028] Dextran sulfate sodium salt (DSS) was purchased from Shanghai Yisheng Biotechnology Co., Ltd.

[0029] 2. Experimental Grouping

[0030] Mice were randomly divided into three groups of five mice each, based on their body weight: a blank control group, a model group, and an experimental group.

[0031] 3. Experimental Methods

[0032] 3.1 Administration method of model-establishing agent

[0033] Blank control group (Ctrl): Free access to water, and daily gavage with sterile drinking water.

[0034] Model group (DSS group): Drinking water containing DSS (2.5% w / v) freely for 8 days.

[0035] Experimental group (Pal group): Drinking water containing DSS (2.5% w / v) was allowed to flow freely for 8 days, while palmitoylcarnitine (4 mg / kg / day) was administered by gavage daily.

[0036] 3.2 Weigh the mice daily, test for fecal occult blood and record the results. Score the mice according to the DAI scoring table (Table 1). The average score of the three items is the Disease Activity Index (DAI).

[0037] Table 1. DAI Scoring Criteria

[0038] score Percentage of weight loss fecal viscosity Fecal occult blood 0 0 standard Negative 1 1～5 Soft but shapely Negative 2 6～10 Soft and unformable Positive 3 11～20 Very soft, damp Bloody stool visible to the naked eye 4 ＞20 Watery diarrhea rectal bleeding

[0039] 3.3 On day 8 of the experiment, mice were euthanized by cervical dislocation. Serum was collected, and the length of the mouse colon was measured and recorded. Colon sections were stained with HE. Mesenteric lymph nodes of mice were collected, and the proportions of CD4+IL17+T cells and CD4+IFNγ+T cells were detected by flow cytometry.

[0040] 4. Experimental Results

[0041] 4.1 Palmitoylcarnitine improves colitis symptoms in mice

[0042] The colon length of each group of mice is as follows: Figure 1 As shown. Figure 1 Diagram showing the colon length for each group. From... Figure 1 It can be seen that, compared with the control group, the colon length of mice in the model group was shortened (P<0.001), while the colon length of the palmitoylcarnitine treatment group was significantly longer than that of the model group (P<0.01), indicating that palmitoylcarnitine significantly improves the colon shortening symptoms caused by colitis in mice.

[0043] Disease activity index of each group of mice as follows: Figure 2 As shown. From Figure 2 It can be seen that, compared with the control group, the disease activity index of mice in the model group increased, and the difference was statistically significant from the fourth day (P<0.05). The disease activity index of the palmitoylcarnitine group was lower than that of the model group, and the difference was statistically significant from the fifth day (P<0.05).

[0044] HE-stained colon sections from each group of mice are shown below. Figure 3 As shown. From Figure 3It can be seen that the model group showed abnormal changes in the morphology of the mucosal epithelium, including inflammatory cell infiltration, submucosal edema, and crypt cysts, while the palmitoylcarnitine group showed significant improvement compared to the model group.

[0045] Figures 1 to 3 The results showed that the model group was successfully modeled and the colitis symptoms in the experimental group were relieved, indicating that palmitoylcarnitine can improve the colitis symptoms in the model mice.

[0046] 4.2 Palmitoylcarnitine increases the proportion of Treg cells in mouse mesenteric lymph nodes.

[0047] The proportion of Treg cells in the intestinal lymph nodes of mice in each group was as follows: Figure 4 As shown. From Figure 4 It can be seen that the proportion of CD4+FOXP3+ T cells in the model was significantly reduced (P<0.05), while the proportion of CD4+FOXP3+ T cells in the palmitoylcarnitine gavage treatment group was increased (P<0.01).

[0048] 4.3 Palmitoylcarnitine reduces the proportion of CD4+IL17+ T cells in the mesenteric lymph nodes of mice.

[0049] The ratio of CD4+IL17+ T cells in the intestinal lymph nodes of mice in each group is as follows: Figure 5 As shown. From Figure 5 It can be seen that the proportion of CD4+IL17+T cells in the model group was significantly increased (P<0.01), while the proportion of CD4+IL17+T cells in the palmitoylcarnitine gavage treatment group was decreased (P<0.05).

[0050] 4.4 Palmitoylcarnitine reduces the proportion of CD4+IFNγ+ T cells in the mesenteric lymph nodes of mice.

[0051] The proportions of CD4+IFNγ+ T cells in the intestinal lymph nodes of mice in each group were as follows: Figure 6 As shown. From Figure 6 It can be seen that the proportion of CD4+IFNγ+ T cells in the model group was significantly increased (P<0.05), while the proportion of CD4+IFNγ+ T cells in the palmitoyl gavage treatment group was decreased (P<0.05).

[0052] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. The use of palmitoylcarnitine as the sole active ingredient in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, wherein the inflammatory bowel disease is ulcerative colitis.

2. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, Among the drugs mentioned for the prevention and / or treatment of inflammatory bowel disease, palmitoylcarnitine improves symptoms of colonic shortening, disease activity index, inflammatory cell infiltration, submucosal edema, and crypt cysts caused by colitis.

3. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, Palmitoylcarnitine improves colitis symptoms by increasing the proportion of Treg cells in mesenteric lymph nodes and decreasing the proportion of CD4+IL17+T cells and CD4+IFNγ+T cells in mesenteric lymph nodes.

4. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, The medicines for the prevention and / or treatment of inflammatory bowel disease also include pharmaceutically acceptable excipients.

5. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, The dosage form of the drug for the prevention and / or treatment of inflammatory bowel disease is any one or more of the following: suspension, granules, capsules, tablets, powders, emulsions, solutions, pellets, injections, suppositories, enemas, aerosols, patches, or drops.

6. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, The administration route of the drug for the prevention and / or treatment of inflammatory bowel disease is any one or more of the following: oral administration, intravenous administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, sublingual administration, transdermal administration, or rectal suppository administration.

7. The use of palmitoylcarnitine as the sole active ingredient according to claim 1 in the preparation of a medicament for the prevention and / or treatment of inflammatory bowel disease, characterized in that, In the aforementioned medication for the prevention and / or treatment of inflammatory bowel disease, the dosage of palmitoylcarnitine is 4 mg / kg / day.

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