Application of R-1, 3-butanediol in preparation of medicine for preventing or treating inflammatory bowel disease

Abstract

The invention relates to the field of biological medicine, in particular to application of R-1, 3-butanediol in preparation of a medicine for preventing or treating inflammatory bowel disease, and the medicine for preventing or treating inflammatory bowel disease is a mixture of R-1, 3-butanediol and normal saline. The R-1, 3-butanediol can be used for preparing the medicine for preventing or treating the inflammatory bowel disease. The 1, 3-butanediol has relatively good effects in the aspects of promoting body weight recovery of colitis patients, reducing colon shortening of the colitis patients, reducing disease activity scores of the colitis patients, reducing intestinal histological scores of the colitis patients, promoting mucosal barrier repair of the colitis patients and inhibiting inflammatory cell infiltration; the compound is especially suitable for prevention and treatment of ulcerative colitis and Crohn's disease.

Description

Technical Field

[0001] The present application relates to the field of biomedicine, and more specifically, to the use of R-1,3-butanediol in the preparation of drugs for preventing or treating inflammatory bowel disease. Background Art

[0002] Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Currently, IBD is mainly treated with the following drugs: 1. Traditional therapeutic drugs: 5-aminosalicylic acid, glucocorticoids, immunomodulators, etc.; 2. Biological agents. However, in clinical practice, traditional drugs are difficult to control the condition of moderate to severe patients and have certain side effects; some patients have primary and secondary drug failure to respond to biological agents, and the cost of biological agents is high. Therefore, the development of a new drug for the treatment of inflammatory bowel disease is a technical problem that needs to be solved urgently. Summary of the invention

[0003] In order to further solve the technical problem of effectively treating inflammatory bowel disease, the present application provides the use of R-1,3-butanediol in the preparation of drugs for preventing or treating inflammatory bowel disease.

[0004] The present application provides the use of R-1,3-butanediol in the preparation of drugs for preventing or treating inflammatory bowel disease.

[0005] Optionally, the drug for preventing or treating inflammatory bowel disease is a mixture of R-1,3-butanediol and normal saline, the concentration of the R-1,3-butanediol anti-inflammatory drug is 80 mg / ml, and it is used by oral gavage.

[0006] Optionally, use of R-1,3-butanediol in promoting weight regain in patients with colitis.

[0007] Optionally, use of R-1,3-butanediol for inhibiting colon shortening in patients with colitis.

[0008] Optionally, use of R-1,3-butanediol in repairing mucosal barriers.

[0009] Optionally, use of R-1,3-butanediol in inhibiting inflammatory cell infiltration.

[0010] Optionally, use of R-1,3-butanediol in reducing disease activity scores in patients with colitis.

[0011] Optionally, use of R-1,3-butanediol in reducing intestinal histological scores in patients with colitis.

[0012] Optionally, use of R-1,3-butanediol in ulcerative colitis and Crohn's disease.

[0013] It should be noted that the structural formula of R-1,3-butanediol is as follows:

[0014] In summary, this application has the following beneficial effects: The R-1,3-butanediol of the present invention can be used to prepare drugs for preventing or treating inflammatory bowel disease. On the one hand, R-1,3-butanediol has good therapeutic effects in promoting weight recovery of patients with colitis, reducing colon shortening of patients with colitis, reducing disease activity scores of patients with colitis, reducing intestinal histological scores of patients with colitis, promoting mucosal barrier repair of patients with colitis and inhibiting inflammatory cell infiltration; on the other hand, R-1,3-butanediol has good therapeutic effects in weight recovery of HMGCS2 gene knockout mice, reducing colon shortening of colitis, etc., especially in the prevention and treatment of ulcerative colitis and Crohn's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 is a schematic diagram of the changes in body weight of three groups of mice over the days in Example 1 of the present application; Figure 2 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 1 of the present application; Figure 3 This is a graph showing the colon length measurements of three groups of mice in Example 1 of the present application; Figure 4 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 1 of the present application; Figure 5 This is a schematic diagram of the scoring results of the three groups of mice in Example 1 of the present application using Table 1; Figure 6 This is a schematic diagram of the scoring results of the three groups of mice in Example 1 of the present application using Table 2; Figure 7 is a cross-sectional view of the colon of mice in the DSS group and the DSS+KE group in Example 1 of the present application; Figure 8 is a schematic diagram of the changes in body weight of three groups of mice over the days in Example 2 of the present application; Fig. 9 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 2 of the present application; Fig.10 This is a graph showing the colon length measurements of three groups of mice in Example 2 of the present application; Fig.11 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 2 of the present application; Fig.12 This is a schematic diagram of the scoring results of the three groups of mice in Example 2 of the present application using Table 1; Fig.13 This is a schematic diagram of the scoring results of the three groups of mice in Example 2 of the present application using Table 3; Fig.14 This is a cross-sectional view of the colon of mice in the TNBS group and the TNBS+KE group in Example 2 of the present application; Fig.15 is a schematic diagram of the changes in body weight of three groups of mice over the days in Example 3 of the present application; Fig.16 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 3 of the present application; Fig.17 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 3 of the present application; Fig.18 This is a schematic diagram of the scoring results of the three groups of mice in Example 3 of the present application using Table 1; Fig.19 This is a schematic diagram of the scoring results of the three groups of mice in Example 3 of the present application using Table 2; Fig. 20 is a schematic diagram of the changes in body weight of three groups of mice over the days in Example 4 of the present application; Fig.21 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 4 of the present application; Fig. 22 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 4 of the present application; Fig.23 This is a schematic diagram of the scoring results of the three groups of mice in Example 4 of the present application using Table 1; Fig.24 This is a schematic diagram of the scoring results of the three groups of mice in Example 4 of the present application using Table 3. DETAILED DESCRIPTION

[0016] The present application is further described in detail with reference to the following examples. It should be noted that if no specific conditions are specified in the following examples, the conventional conditions or the conditions recommended by the manufacturer are followed, and the raw materials used in the following examples can be obtained from common commercial sources unless otherwise specified.

[0017] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.

[0018] In this application, "first aspect", "second aspect", "third aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0019] In this application, "optionally", "optional", and "optional" mean optional or dispensable, that is, any one of the two parallel schemes of "yes" or "no". If multiple "options" appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "optional" is independent.

[0020] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0021] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0022] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as those commonly understood by technicians in the technical field of this application. The terms used in this application and in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used in this application includes any and all combinations of one or more related listed items. The term "multiple" in this application means at least two, such as two, three, etc., unless otherwise clearly and specifically limited.

[0023] It is noted that the raw materials used in this application are all commercially available.

[0024] Example Example 1 Experimental study on the treatment of acute colitis induced by dextran sulfate sodium (DSS) in mice with R-1,3-butanediol 1 Experimental methods 1.1 Experimental Animal Grouping 17 healthy mice were selected and divided into three groups, namely: control group (represented by control in the attached drawings of the specification), DSS group, and DSS+R-1,3-butanediol group (hereinafter abbreviated as DSS+KE). There were 5 mice in the control group and DSS group, and 7 mice in DSS+KE. Specifically, the control group consisted of normally raised healthy mice, which were not given R-1,3-butanediol by gavage or dextran sodium sulfate solution; the DSS group consisted of mice fed with dextran sodium sulfate solution but not R-1,3-butanediol by gavage; the DSS+KE group consisted of mice given R-1,3-butanediol by gavage and dextran sodium sulfate solution by gavage.

[0025] 1.2 Construction of DSS colitis model (1) Starting one week before formal modeling, mice in the DSS+KE group were gavaged with R-1,3-butanediol anti-inflammatory drug every day. The R-1,3-butanediol anti-inflammatory drug was a mixed solution of R-1,3-butanediol and normal saline. The concentration of R-1,3-butanediol anti-inflammatory drug was 80 mg / ml, that is, 80 mg of R-1,3-butanediol was dissolved in every ml of normal saline. The mice were gavaged with R-1,3-butanediol anti-inflammatory drug according to their body weight, specifically 0.4 mg of R-1,3-butanediol per gram of mouse body weight. The mice in the other two groups were gavaged with an equal amount of normal saline. After gavage, the three groups of mice were fed and weighed normally.

[0026] (2) Starting from the first day of formal modeling, mice in the DSS group and DSS+KE group were fed with DSS solution every day. The DSS solution was prepared by mixing DSS powder with sterile water. The concentration of DSS solution was 2.5% mass / volume fraction (w / vol). 200 ml of DSS solution was prepared, and mice drank about 5 ml per day. The control group was fed with sterile water. All three groups had free access to drinking water.

[0027] (3) On the 3rd and 5th days of formal modeling, record the remaining amount in the water bottle, discard it and replace it with the newly prepared DSS solution to prevent the DSS solution from being left for a long time and possibly affecting its normal performance.

[0028] (4) On the 8th day, remove the DSS solution and replace it with sterile water.

[0029] (5) On days 9-11, the mice were anesthetized and killed by cervical dislocation to complete the sampling.

[0030] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria Starting from the first day of formal modeling, the three groups of mice were weighed every day, and the texture of feces and bloody stools were observed. Attention was paid to the basic health conditions of the mice with bloody stools, such as vitality, body temperature, and coat color. Fecal occult blood was detected using a test kit, and the mortality rate of mice was counted on the last day of modeling.

[0031] The killed mice were soaked in 75% ethanol, and the abdomen was opened with ophthalmic scissors to expose the abdominal cavity. The colon was quickly removed and its general condition was observed. The length of the mouse colon from the ileocecal valve to the end of the rectum was measured, and the colon was cut crosswise after being photographed and recorded. Another 5 mm was cut for 4% paraformaldehyde fixation and subsequent embedding and slicing.

[0032] Table 1 Disease Activity Index (DAI) score table for mouse enteritis

[0033] Table 2 DSS colon inflammation-related histological scores system

[0034] The three groups of mice were scored according to the mouse enteritis disease activity index (DAI) scoring table in Table 1, and the three groups of mice were scored according to the DSS colon inflammation-related histological scoring system in Table 2. The sum of the scores in the left and right columns of Table 2 is the comprehensive score of the histological score. The comprehensive score ranges from 0 to 6. 0 points indicates that the health status of the mouse has not changed, and 6 points indicates that there is extensive inflammatory infiltration and tissue damage in the colon of the mouse.

[0035] 1.4 Experimental Results Dextran sulfate sodium (DSS) can cause ulcerative colitis in mice, with specific symptoms including bloody stools, weight loss, shortened colon length, increased disease activity score, increased histopathology score, mucosal barrier destruction and inflammatory cell infiltration.

[0036] See also Figure 1 and Figure 2 After the 4th day, there was no significant change in the body weight of the mice in the control group (control), while the body weight of the mice in the DSS group and the DSS+KE group began to decrease. However, the weight of the mice in the DSS+KE group decreased more slowly than that in the DSS group. In other words, oral administration of the anti-inflammatory drug R-1,3-butanediol can promote the recovery of the body weight of mice with acute DSS colitis.

[0037] See also Figure 3 and Figure 4 The colon length of mice in the DSS group and DSS+KE group was shorter than that of the control mice, but the average length of the colon of the DSS+KE group was 1 cm longer than that of the DSS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drug can slow down the shortening of the colon in mice with acute DSS colitis.

[0038] See also Figure 5The three groups of mice were scored using the mouse colitis disease activity index (DAI) scoring table in Table 1. The average DAI score of the DSS+KE group was 0.8 lower than that of the DSS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drugs can prevent and improve the diarrhea and bloody stool symptoms of mice with acute DSS colitis.

[0039] See also Figure 6 The three groups of mice were scored using the DSS colon inflammation-related histological scores system in Table 2. The average DAI score of the DSS+KE group was 2 lower than that of the DSS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drug can reduce the DSS colon inflammation-related histological scores of mice with acute DSS colitis.

[0040] See also Figure 7 The comparison of the microscopic tissues of mice in the DSS+KE group and the DSS group showed that oral administration of the anti-inflammatory drug R-1,3-butanediol could prevent and improve tissue damage, mucosal barrier destruction and inflammatory cell infiltration in mice with acute DSS colitis.

[0041] It can be seen that oral administration of R-1,3-butanediol anti-inflammatory drug based on acute DSS modeling can prevent and improve intestinal inflammation in mice.

[0042] Example 2 Experimental study on the treatment of TNBS-induced acute colitis mouse model with R-1,3-butanediol 1 Experimental methods 1.1 Experimental Animal Grouping Thirteen healthy male mice were selected and divided into three groups, namely: a control group (marked as control in the attached figure), a 2,4,6-trinitrobenzenesulfonic acid group (hereinafter abbreviated as TNBS group), and a TNBS+R-1,3-butanediol group (hereinafter abbreviated as TNBS-KE group). Specifically, the control group was healthy mice raised normally.

[0043] 1.2 Construction of TNBS colitis model and drug administration (1) Healthy mice were randomly divided into different groups, marked with ear tags, and kept in the animal room for 1 week to allow them to acclimate to the environment.

[0044] (2) Presensitization: Preparation of control pre-sensitization solution: Use acetone and olive oil in a volume ratio of 4:1 to prepare the control pre-sensitization solution.

[0045] Preparation of pre-sensitization solution: 1% TNBS pre-sensitization solution was prepared by using 5% TNBS solution and control pre-sensitization solution in a volume ratio of 1:4, and vortexed to mix.

[0046] An electric shaver was used to shave the hair between the shoulder blades of the mice to expose a skin area of ​​approximately 1.5 cm × 1.5 cm. Each mouse in the TNBS group and TNBS-KE group was dripped with 150 μL of 1% TNBS pre-sensitization solution on the exposed skin area, and the mice in the control group were dripped with an equal volume of control pre-sensitization solution. At the same time, the mice in the TNBS-KE group were gavaged with R-1,3-butanediol anti-inflammatory drug, and the configuration concentration and dosage of R-1,3-butanediol anti-inflammatory drug were the same as in Example 1. The control group and the TNBS group were gavaged with an equal amount of normal saline, and the mice were fed and weighed normally after gavage.

[0047] (3) Formal enema modeling: One week after pre-sensitization, that is, on the 8th day, mice were given enema. The mice were fasted the day before enema, and the day of enema was recorded as day 1. 2.5% TNBS enema solution was prepared by using 5% TNBS solution and anhydrous ethanol in a volume ratio of 1:1. The control group used physiological saline and anhydrous ethanol in a volume ratio of 1:1 to prepare 50% ethanol solution.

[0048] Before enema, mice were stimulated to defecate so that enema could be performed smoothly later. The enema device was assembled, and the enema catheter, syringe and connector were installed. The mice were anesthetized using a mouse gas anesthesia machine. The mouse tail was lifted, and the enema tube was evenly lubricated with paraffin oil. The tube mouth was inserted into the mouse anus, and the rectum and colon were slowly and carefully inserted gradually to avoid damaging the intestinal tract. While inserting the tube, 2.5% TNBS solution was pushed in with a syringe. The movements were gentle to avoid stimulating the mice and causing the liquid to overflow from the intestine. After entering 4 cm, the tube was withdrawn. Each mouse in the TNBS group and TNBS-KE group was given 100 µL of enema solution, and the mice in the control group were given an equal volume of 50% ethanol solution enema. After the operation was completed, the anesthetized mice were inverted for 1 min to prevent the liquid from flowing out, and then put back into the mouse cage to wait for them to wake up.

[0049] 1.3 Experimental animal tissue sample preparation and scoring criteria The observation and sampling contents were the same as those in Example 1. The three groups of mice were scored using Table 1 in Example 1, and the three groups of mice were scored using the TNBS colitis inflammation-related histological scoring system in Table 3.

[0050] Table 3 TNBS colitis inflammation-related histological scoring system

[0051] 1.4 Experimental Results Effects of R-1,3-butanediol on acute TNBS colitis in mice.

[0052] 2,4,6-Trinitrobenzenesulfonic acid (TNBS) can cause Crohn's disease-like colitis in mice, which is manifested by bloody stools, weight loss, shortened colon length, increased disease activity scores, increased histopathological scores, mucosal barrier destruction and inflammatory cell infiltration.

[0053] See also Figure 8 and Fig. 9 The weight of mice in the control group remained stable, while the weight of mice in the TNBS group and TNBS+KE group decreased. However, from day 2.5 to day 4, the weight of mice in the TNBS+KE group decreased slowly compared with the TNBS group, especially from day 4 to day 5, the weight of mice in the TNBS+KE group increased significantly, and on day 5, the weight was close to that of mice in the control group. In other words, oral administration of R-1,3-butanediol anti-inflammatory drug can promote the weight of TNBS colitis mice to return to normal, and it is effective in recovering the weight of TNBS colitis mice.

[0054] See also Fig.10 and Fig.11 The colon length of mice in the TNBS group and the TNBS+KE group was shorter than that of the control mice, but the average colon of the mice in the TNBS+KE group was nearly 1 cm longer than that of the TNBS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drug can prevent and slow down the shortening of the colon in TNBS colitis mice.

[0055] See also Fig.12 The three groups of mice were scored using the mouse colitis disease activity index (DAI) scoring table in Table 1. The average DAI score of the mice in the TNBS+KE group was 1.9 lower than that in the TNBS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drugs can prevent and improve the diarrhea and bloody stool symptoms of mice with acute TNBS colitis.

[0056] See also Fig.13 The three groups of mice were scored using the TNBS colitis inflammation-related histological scoring system in Table 3. The average DAI score of the mice in the TNBS+KE group was lower than that in the TNBS group, indicating that oral administration of R-1,3-butanediol anti-inflammatory drug can reduce the TNBS colon inflammation-related histological score of TNBS colitis mice.

[0057] See also Fig.14 The comparison of the microscopic tissues of mice in the TNBS + KE group and the TNBS group showed that oral administration of the anti-inflammatory drug R-1,3-butanediol could reduce intestinal inflammation in TNBS colitis mice and play a role in repairing the intestinal barrier.

[0058] It can be seen that oral administration of R-1,3-butanediol anti-inflammatory drug based on acute TNBS modeling can improve intestinal inflammation in mice.

[0059] Example 3 Effects of HMGCS2 gene knockout and R-1,3-butanediol supplementation on colitis in DSS mice 1 Experimental methods 1.1 Experimental Animal Grouping Twenty male mice were selected and divided into three groups: wild-type DSS model group (i.e., WT-DSS group), gene knockout mouse DSS model group (i.e., KO-DSS group) and R-1,3-butanediol-intervention gene knockout mouse DSS model group (i.e., KO-DSS-KE group).

[0060] 1.2 Experimental animal model establishment and drug administration Same as Example 1.

[0061] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria Same as Example 1.

[0062] 1.4 Experimental Results Effects of HMGCS2 gene knockout and R-1,3-butanediol anti-inflammatory drug supplementation on colitis in DSS mice.

[0063] See also Fig.15 and Fig.16 The weight of mice in all three groups decreased. However, the weight of mice in the KO-DSS-KE group decreased more slowly than that in the other two groups. In particular, the weight of mice in the KO-DSS-KE group decreased significantly more slowly than that in the KO-DSS group. In other words, exogenous supplementation with the anti-inflammatory drug R-1,3-butanediol can slow down the further weight loss of mice with colitis caused by HMGCS2 gene knockout and promote the weight recovery of HMGCS2 gene knockout mice.

[0064] See also Fig.17 The colon length of mice in the KO-DSS-KE group was about 0.8 cm longer than that in the KO-DSS group on average, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can prevent and slow down the further shortening of the colon of mice with colitis caused by HMGCS2 gene knockout.

[0065] See also Fig.18 The three groups of mice were scored using the mouse enteritis disease activity index (DAI) scoring table in Table 1. The DAI score of the KO-DSS-KE group was 1 lower than that of the KO-DSS group on average, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can reduce the DAI score of HMGCS2 gene knockout mice and prevent and improve the diarrhea and bloody stool symptoms of HMGCS2 gene knockout mice.

[0066] See also Fig.19 The three groups of mice were scored using the DSS colon inflammation-related histological scores system in Table 2. The average DAI score of the KO-DSS-KE group was 3 lower than that of the KO-DSS group, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can reduce the DSS colon inflammation-related histological scores of HMGCS2 gene knockout mice.

[0067] It can be seen that HMGCS2 intestinal epithelium-specific knockout mice are more sensitive to DSS than the same littermate control mice. Exogenous supplementation with R-1,3-butanediol can compensate for the weight loss, reduced colon shortening, increased disease activity, and increased histological scores caused by the loss of the HMGCS2 gene.

[0068] Example 4 Effects of HMGCS2 gene knockout and R-1,3-butanediol supplementation on colitis in TNBS mice 1 Experimental methods 1.1 Experimental Animal Grouping Seventeen healthy male mice were selected and divided into three groups: wild-type TNBS model group (i.e., WT-TNBS group), HMGCS2 gene knockout mouse TNBS model group (i.e., KO-TNBS group), and R-1,3-butanediol treatment agent intervention HMGCS2 gene knockout mouse TNBS model group (i.e., KO-TNBS-KE group).

[0069] 1.2 Experimental animal model establishment and drug administration Same as Example 2.

[0070] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria Same as Example 2.

[0071] 1.4 Experimental Results Effects of HMGCS2 gene knockout and R-1,3-butanediol therapeutic supplementation on colitis in TNBS mice.

[0072] See also Fig. 20 and Fig.21 The body weight of the three groups of mice showed an overall downward trend. However, from the third day, the body weight of the mice in the KO-TNBS-KE group began to increase, and on the fourth day, the body weight increased to the same as that of the mice in the WT-TNBS group. In other words, exogenous supplementation with R-1,3-butanediol anti-inflammatory drug can slow down the further weight loss of TNBS colitis mice caused by HMGCS2 gene knockout and promote the recovery of body weight in HMGCS2 gene knockout mice.

[0073] See also Fig. 22The average colon length of mice in the KO-TNBS-KE group was about 0.8 cm longer than that in the KO-TNBS group, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can prevent and slow down the further shortening of the colon of mice with colitis caused by HMGCS2 gene knockout.

[0074] See also Fig.23 The three groups of mice were scored using the mouse enteritis disease activity index (DAI) scoring table in Table 1. The average DAI score of the mice in the KO-TNBS-KE group was 0.9 lower than that in the KO-TNBS group, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can reduce the DAI score of HMGCS2 gene knockout mice and prevent and improve the diarrhea and bloody stool symptoms of HMGCS2 gene knockout mice.

[0075] See also Fig.24 The three groups of mice were scored using the TNBS colitis inflammation-related histology scoring system in Table 3. The average TNBS colon inflammation-related histology score of the KO-TNBS-KE group was 1.8 lower than that of the KO-TNBS group, indicating that the use of R-1,3-butanediol anti-inflammatory drug as an exogenous supplement can reduce the TNBS colon inflammation-related histology score of HMGCS2 gene knockout mice.

[0076] It can be seen that HMGCS2 intestinal epithelium-specific knockout mice are more sensitive to TNBS than their littermates in the WT-TNBS group. Exogenous supplementation with R-1,3-butanediol therapeutic agent can compensate for the lower body weight, reduced colon shortening, increased disease activity, and increased pathological scores caused by the lack of HMGCS2.

[0077] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed. However, as long as it is within the scope of the claims of the present application, it shall be protected by the patent law.

Claims

1. Application of R-1,3-butanediol in the preparation of drugs for preventing or treating inflammatory bowel disease.

2. The use according to claim 1, characterized in that: The drug for preventing or treating inflammatory bowel disease is a mixture of R-1,3-butanediol and physiological saline.

3. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in promoting weight recovery in patients with colitis.

4. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in inhibiting colon shortening in patients with colitis.

5. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in repairing mucosal barriers.

6. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in inhibiting inflammatory cell infiltration.

7. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in reducing the disease activity score of colitis patients.

8. The use according to claim 1, characterized in that: The application of R-1,3-butanediol in reducing the intestinal histological score of patients with colitis.

9. The use according to claim 1, characterized in that: The R-1,3-butanediol is administered by intragastric administration.

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