Application of acetyl carnitine in preparation of medicine for preventing and / or treating inflammatory bowel disease

Abstract

The invention relates to the field of biological medicines, in particular to application of acetyl carnitine in preparation of a medicine for preventing and / or treating inflammatory bowel diseases. The acetyl carnitine is simple in synthesis process, low in preparation cost and free of obvious toxic and side effects. The colitis symptom can be comprehensively improved by increasing the cell proportion of regulatory T cells (Treg) in mesenteric lymph nodes and reducing the level of proinflammatory factors such as IL17 and IFN gamma, and the compound can be applied to preparation of drugs for preventing and / or treating inflammatory bowel diseases.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to the application of acetyl carnitine in the preparation of medicines for preventing and / or treating inflammatory bowel disease. Background Art

[0002] Acetylcarnitine is an organic compound of carnitine, which has many uses in the field of medical and health products. It is widely used as a dietary supplement to improve physical fitness, improve energy metabolism, enhance athletic ability and reduce fatigue. It is also used to treat neurological diseases, depression and memory loss. As the pharmacological effects of acetylcarnitine become increasingly apparent, new uses of acetylcarnitine are also in urgent need of development.

[0003] Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. Ulcerative colitis has a complex pathogenesis, a protracted course of disease, and is often accompanied by continuous inflammatory lesions and fibrous scars in the colonic mucosa and submucosa, as well as mucosal erosions, crypt abscesses, etc. It is currently believed that ulcerative colitis is related to multiple factors such as genetics, environment, and immunity, and there is currently no cure. The main drugs currently used in clinical treatment of ulcerative colitis include aminosalicylic acids, hormones, and immunosuppressants, but there are still problems such as limited efficacy, long treatment cycles, and high recurrence rates, and there are usually serious complications.

[0004] However, there are no reports on the anti-inflammatory bowel disease activity and mechanism of action of acetylcarnitine. Summary of the invention

[0005] The purpose of the present invention is to provide a new use of acetyl carnitine in the treatment and prevention of inflammatory bowel disease. Increased fat intake can cause inflammatory changes in the colon. As an important intermediate metabolite of fatty acid oxidation, acetyl carnitine has important research value and clinical significance in the treatment and prevention of inflammatory bowel disease.

[0006] In order to achieve the above object, the first aspect of the present invention provides the use of acetyl carnitine in the preparation of a medicament for preventing and / or treating inflammatory bowel disease.

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

[0008] Furthermore, in the drug for preventing and / or treating inflammatory bowel disease, acetylcarnitine improves the symptoms of colon shortening, disease activity index, inflammatory cell infiltration, intestinal villus and crypt structure caused by colitis; acetylcarnitine comprehensively improves the symptoms of colitis by increasing the proportion of FOXP3+Treg cells in the mesentery and reducing the proportion of CD4+IL17+T cells and the proportion of CD4+IFNγ+T cells.

[0009] Furthermore, the drug for preventing and / or treating inflammatory bowel disease uses acetylcarnitine as the only active monomer component, or acetylcarnitine is used in combination with other drugs to form a pharmaceutical composition.

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

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

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

[0013] The second aspect of the present invention provides a drug for preventing and / or treating inflammatory bowel disease, wherein the drug contains acetylcarnitine as the only active monomer component, or acetylcarnitine is used in combination with other drugs to form a pharmaceutical composition.

[0014] The present invention has the advantages that:

[0015] The acetylcarnitine involved in the present invention has a simple synthesis process, low preparation cost, and small toxic and side effects. It can comprehensively improve the symptoms of colitis by increasing the cell ratio of regulatory T cells (Treg) in mesenteric lymph nodes and reducing the levels of pro-inflammatory factors such as IL17 and IFNγ, and can be used to prepare drugs for preventing and / or treating inflammatory bowel disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Schematic diagram of the colon length of each group of mice (from left to right: control group, DSS group, DSS+Ace group; the results shown in the figure are mean±SEM, n=5).

[0017] Figure 2 Schematic diagram of the disease activity index of each group of mice (the horizontal axis represents the number of treatment days, the vertical axis represents the disease activity index; * represents compared with the control group, # represents compared with the model group; the results shown in the figure are mean ± SEM, n = 5).

[0018] Figure 3Schematic diagram of HE staining of colon sections of mice in each group (from left to right: control group, DSS group, DSS+Ace group; magnification: 200 times).

[0019] Figure 4 Schematic diagram of the proportion of CD4+FOXP3+Treg cells in the mesenteric lymph nodes of each group of mice (from left to right: control group, DSS group, DSS+Ace group; the results shown in the figure are mean±SEM, n=5).

[0020] Figure 5 Schematic diagram of the proportion of CD4+IL17+T cells in the mesenteric lymph nodes of each group of mice (from left to right: control group, DSS group, DSS+Ace group; the results shown in the figure are mean ± SEM, n = 5).

[0021] Figure 6 Schematic diagram of the proportion of CD4+IFNγ+T cells in the mesenteric lymph nodes of each group of mice (from left to right: control group, DSS group, DSS+Ace group; the results shown in the figure are mean±SEM, n=5). DETAILED DESCRIPTION

[0022] The specific implementation methods provided by the present invention are described in detail below in conjunction with examples.

[0023] Example:

[0024] 1. Experimental materials:

[0025] Fifteen C57 / BL6 mice (male, 8 weeks old) were purchased from Shanghai Bio-Tech Biotechnology Co., Ltd.

[0026] Acetylcarnitine hydrochloride was purchased from Sangon Biotechnology Co., Ltd. (A603004).

[0027] Dextran Sulfate Sodium Salt (DSS) was purchased from Shanghai Yisheng Biotechnology Co., Ltd.

[0028] 2. Experimental groups:

[0029] The mice were randomly divided into 3 groups according to their body weight, with 5 mice in each group, namely blank control group, model group and experimental group.

[0030] 3. Experimental methods:

[0031] 3.1 Administration method of model establishment agent

[0032] Blank control group (Ctrl): free access to water, and intragastric administration of sterile drinking water every day.

[0033] Model group (DSS group): The mice were allowed to drink freely the drinking water containing DSS (2.5% w / v) for 8 days.

[0034] Experimental group (Ace group): The mice were allowed to drink freely the drinking water containing DSS (2.5% w / v) for 8 days, and acetylcarnitine hydrochloride (200 mg / kg / day) was given by gavage every day.

[0035] 3.2 The mice were weighed and fecal occult blood was tested and recorded every day, and scored according to the DAI scoring table (Table 1). The average score of the three items was the Disease Activity Index (DAI).

[0036] Table 1. DAI scoring criteria

[0037]

[0038]

[0039] 3.3 On the 8th day of the experiment, the mice were killed by cervical dislocation, serum was collected, the colon was measured and its length was recorded, and the colon sections were HE stained; the mesenteric lymph nodes of the mice were collected, and the proportion of CD4+IL17+T cells and CD4+IFNγ+T cells were detected by flow cytometry.

[0040] 4. Experimental results:

[0041] 4.1 Acetylcarnitine improves colitis symptoms in mice

[0042] The colon length of each group of mice was Figure 1 shown. Figure 1 Schematic diagram of colon length in each group. Figure 1 It can be seen that compared with the control group, the colon length of the model group mice was shortened (P < 0.05), while the colon length of the acetyl carnitine-treated group was significantly longer than that of the model group (P < 0.01), indicating that acetyl carnitine significantly improved the symptoms of colon shortening caused by colitis in mice.

[0043] The disease activity index of each group of mice was Figure 2 As shown. Figure 2 It can be seen that compared with the control group, the disease activity index of the model group mice increased from the fourth day of modeling (P < 0.001); the disease activity index of the Ace-treated group was lower than that of the model group, and the difference was statistically significant from the seventh day (P < 0.01).

[0044] HE staining of colon sections of mice in each group is shown in Figure 3 As shown. Figure 3It can be seen that the model group showed abnormal changes in mucosal epithelial morphology, inflammatory cell infiltration, submucosal edema, and crypt cysts, while the Ace group showed significant improvement compared with the model group, that is, the inflammatory cell infiltration was reduced, and the intestinal villi and crypt structure were restored.

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

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

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

[0048] 4.3 Acetylcarnitine 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 each group of mice was as follows Figure 5 As shown. Figure 5 It can be seen that compared with the control group, the proportion of CD4+IL17+T cells in the model group was significantly increased, while the proportion of CD4+IL17+T cells in the Ace gavage treatment group was decreased.

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

[0051] The ratio of CD4+IL17+T cells in the intestinal lymph nodes of each group of mice was as follows Figure 6 As shown. Figure 6 It can be seen that the proportion of CD4+IFNγ+T cells in the model group increased significantly (P<0.05); while the proportion of CD4+IFNγ+T cells in the Ace gavage treatment group decreased (P<0.05).

[0052] The preferred embodiments of the present invention have been specifically described above, but the present invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. Use of acetylcarnitine in the preparation of a drug for preventing and / or treating inflammatory bowel disease.

2. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: The inflammatory bowel disease is ulcerative colitis or Crohn's disease.

3. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: In the drug for preventing and / or treating inflammatory bowel disease, acetyl carnitine improves the symptoms of colon shortening, disease activity index, inflammatory cell infiltration, intestinal villi and crypt structure caused by colitis.

4. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: Acetylcarnitine comprehensively improves colitis symptoms by increasing the proportion of FOXP3+Treg cells in the mesentery and reducing the proportion of CD4+IL17+T cells and CD4+IFNγ+T cells.

5. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: The drug for preventing and / or treating inflammatory bowel disease uses acetylcarnitine as the only active monomer component, or acetylcarnitine is used in combination with other drugs to form a drug composition.

6. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: The drug for preventing and / or treating inflammatory bowel disease also includes pharmaceutically acceptable excipients.

7. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: The dosage form of the drug for preventing and / or treating inflammatory bowel disease is any one or more of suspension, granules, capsules, tablets, powders, emulsions, solutions, pills, injections, suppositories, enemas, aerosols, patches or drops.

8. The use of acetyl carnitine according to claim 1 in the preparation of a medicament for preventing and / or treating inflammatory bowel disease, characterized in that: The administration route of the drug for preventing and / or treating inflammatory bowel disease is any one or more of oral administration, intravenous administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, sublingual administration, transdermal administration or rectal suppository administration.

9. A drug for preventing and / or treating inflammatory bowel disease, characterized in that: The medicine is a medicine composition composed of acetylcarnitine as the only active monomer component, or acetylcarnitine is used in combination with other medicines.

Images