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

Abstract

The present application relates to the field of biomedicine, and more particularly to the use of R-1,3-butanediol in the preparation of a drug for the prevention or treatment of inflammatory bowel disease, wherein the drug for the prevention or treatment of inflammatory bowel disease is a mixture of R-1,3-butanediol and normal saline. R-1,3-butanediol can be used to prepare a drug for the prevention or treatment of inflammatory bowel disease. R-1,3-butanediol has good effects in promoting weight gain in patients with colitis, reducing colon shortening in patients with colitis, reducing disease activity scores in patients with colitis, reducing intestinal histological scores in patients with colitis, promoting mucosal barrier repair in patients with colitis, and inhibiting inflammatory cell infiltration, particularly in the 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) primarily includes Crohn's disease (CD) and ulcerative colitis (UC). Currently, IBD is primarily treated with the following medications: 1. Traditional treatments: 5-aminosalicylic acid, glucocorticoids, immunomodulators, etc.; 2. Biologics. However, in clinical practice, traditional medications struggle to control moderate to severe disease and are associated with side effects. Biologics can cause both primary and secondary drug failure in some patients, and they are expensive. Therefore, the development of new drugs to treat IBD is a pressing technical challenge. 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 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 in 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]

[0015] In summary, this application has the following beneficial effects:

[0016] The R-1,3-butanediol of the present invention can be used to prepare a drug for preventing or treating inflammatory bowel disease. On the one hand, R-1,3-butanediol has good therapeutic effects in promoting weight recovery in patients with colitis, reducing colon shortening in patients with colitis, reducing disease activity scores in patients with colitis, reducing intestinal histological scores in patients with colitis, promoting mucosal barrier repair in patients with colitis, and inhibiting inflammatory cell infiltration. On the other hand, R-1,3-butanediol has good therapeutic effects in weight recovery and reducing colon shortening in HMGCS2 gene knockout mice, especially in the prevention and treatment of ulcerative colitis and Crohn's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Schematic diagram of the changes in body weight of three groups of mice over time in Example 1 of the present application;

[0018] 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;

[0019] Figure 3 This is a graph showing the colon length measurements of three groups of mice in Example 1 of the present application;

[0020] Figure 4 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 1 of the present application;

[0021] 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;

[0022] 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;

[0023] Figure 7 This 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;

[0024] Figure 8 Schematic diagram of the changes in body weight of three groups of mice over time in Example 2 of the present application;

[0025] Figure 9 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 2 of the present application;

[0026] Figure 10 This is a graph showing the colon length measurements of three groups of mice in Example 2 of the present application;

[0027] Figure 11 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 2 of the present application;

[0028] Figure 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;

[0029] Figure 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;

[0030] Figure 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;

[0031] Figure 15 Schematic diagram of the changes in body weight of three groups of mice over time in Example 3 of the present application;

[0032] Figure 16 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 3 of the present application;

[0033] Figure 17 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 3 of the present application;

[0034] Figure 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;

[0035] Figure 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;

[0036] Figure 20 This is a schematic diagram showing the changes in body weight of three groups of mice over time in Example 4 of the present application;

[0037] Figure 21 This is a schematic diagram comparing the final body weights of the three groups of mice in Example 4 of the present application;

[0038] Figure 22 This is a schematic diagram comparing the colon lengths of the three groups of mice in Example 4 of the present application;

[0039] Figure 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;

[0040] Figure 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

[0041] The present application is further described in detail with reference to the following examples. It is particularly noted that if no specific conditions are specified in the following examples, the experiments were carried out according to conventional conditions or those recommended by the manufacturer. Unless otherwise specified, the raw materials used in the following examples can be obtained from common commercial sources.

[0042] To make the above-mentioned objects, features, and advantages of the present application more clearly understood, the specific embodiments of the present application are described in detail below. The following description sets forth many specific details to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways than those described herein, and those skilled in the art can make similar modifications without violating the scope of the present application. Therefore, the present application is not limited to the specific embodiments disclosed below.

[0043] In this application, terms such as "first aspect," "second aspect," and "third aspect" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor as implicitly indicating the importance or quantity of the technical features indicated. Furthermore, terms such as "first," "second," and "third," etc., are intended only to provide a non-exhaustive enumeration and description and should not constitute a closed-ended limitation on quantity.

[0044] In this application, the terms "optionally," "optional," and "optional" mean optional or dispensable, i.e., they refer to either option being selected from two parallel options: "with" or "without." If a technical solution contains multiple "optional" clauses, each "optional" clause is independent unless otherwise specified and there are no contradictions or constraints.

[0045] In this application, when referring to numerical ranges, unless otherwise specified, the numerical ranges are considered continuous and include the minimum and maximum values ​​of the range, as well as every value between such minimum and maximum values. Further, when a range refers to an integer, every integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe a feature or characteristic, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges subsumed therein.

[0046] In this 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.

[0047] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by those skilled in the art to which this application belongs. 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 defined.

[0048] The raw materials used in this application are all commercially available.

[0049] Example

[0050] Example 1

[0051] Experimental study on the treatment of acute colitis model induced by dextran sulfate sodium (DSS) by R-1,3-butanediol

[0052] 1 Experimental methods

[0053] 1.1 Experimental Animal Grouping

[0054] Seventeen healthy mice were selected and divided into three groups: a control group (represented by "control" in the accompanying drawings), a DSS group, and a DSS+R-1,3-butanediol group (hereinafter abbreviated as DSS+KE). Both the control and DSS groups consisted of five mice, while the DSS+KE group consisted of seven mice. Specifically, the control group consisted of normally housed healthy mice that were not given R-1,3-butanediol or dextran sulfate sodium solution by gavage; the DSS group consisted of mice that were given dextran sulfate sodium solution but not R-1,3-butanediol by gavage; and the DSS+KE group consisted of mice that were given R-1,3-butanediol and dextran sulfate sodium solution by gavage.

[0055] 1.2 Construction of DSS colitis model

[0056] (1) Starting one week before the 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 each 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.

[0057] (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 the DSS solution was 2.5% mass / volume fraction (w / vol). 200 ml of DSS solution was prepared, and mice drank about 5 ml every day. The control group was fed with sterile water. All three groups had free access to water.

[0058] (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.

[0059] (4) On the 8th day, remove the DSS solution and replace it with sterile water.

[0060] (5) On days 9-11, the mice were anesthetized and killed by cervical dislocation to complete the sampling.

[0061] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria

[0062] 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. The basic health conditions of mice with bloody stools, such as vitality, body temperature, and coat color, were noted. Fecal occult blood was detected using a test kit, and the mortality rate of mice was counted on the last day of modeling.

[0063] The sacrificed 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 gross 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 transversely cut after taking pictures and recording. Another 5 mm was cut for 4% paraformaldehyde fixation and subsequent embedding and slicing.

[0064] Table 1 Disease Activity Index (DAI) score for mouse enteritis

[0065]

[0066] Table 2 DSS colon inflammation-related histological scores system

[0067]

[0068] The three groups of mice were scored according to the mouse enteritis disease activity index (DAI) scoring table in Table 1 and 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, where 0 indicates that the health status of the mouse remains unchanged and 6 indicates that there is extensive inflammatory infiltration and tissue damage in the mouse colon.

[0069] 1.4 Experimental Results

[0070] Dextran sulfate sodium (DSS) can cause ulcerative colitis in mice, with symptoms including bloody stools, weight loss, shortened colon length, increased disease activity score, increased histopathology score, mucosal barrier destruction and inflammatory cell infiltration.

[0071] See also Figure 1 and Figure 2 After the 4th day, there was no significant change in the weight of the mice in the control group, while the 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 weight of mice with acute DSS colitis.

[0072] 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.

[0073] See also Figure 5 The three groups of mice were scored using the mouse colitis disease activity index (DAI) score 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 drug can prevent and improve the diarrhea and bloody stool symptoms of mice with acute DSS colitis.

[0074] 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.

[0075] 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 R-1,3-butanediol anti-inflammatory drug could prevent and improve tissue damage, mucosal barrier destruction and inflammatory cell infiltration in mice with acute DSS colitis.

[0076] 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.

[0077] Example 2

[0078] Experimental study on the treatment of TNBS-induced acute colitis mouse model with R-1,3-butanediol

[0079] 1 Experimental methods

[0080] 1.1 Experimental Animal Grouping

[0081] Thirteen healthy male mice were selected and divided into three groups: a control group (labeled "control" in the accompanying figures), a 2,4,6-trinitrobenzenesulfonic acid group (hereinafter referred to as the TNBS group), and a TNBS + R-1,3-butanediol group (hereinafter referred to as the TNBS-KE group). Specifically, the control group consisted of normally housed healthy mice.

[0082] 1.2 Construction of TNBS colitis model and drug administration

[0083] (1) Healthy mice were randomly divided into different groups, ear-tagged, and kept in the animal room for 1 week to allow them to adapt to the environment.

[0084] (2) Presensitization:

[0085] Prepare the control pre-sensitization solution: prepare the control pre-sensitization solution using acetone and olive oil in a volume ratio of 4:1.

[0086] Prepare the pre-sensitization solution: prepare 1% TNBS pre-sensitization solution by using 5% TNBS solution and control pre-sensitization solution in a volume ratio of 1:4, and vortex to mix.

[0087] The mice were shaved between their scapulae using an electric razor, exposing an approximately 1.5 cm × 1.5 cm skin area. Each mouse in the TNBS and TNBS-KE groups was primed with 150 µL of 1% TNBS solution, applied to the exposed skin area. The control group received an equal volume of the control solution. Simultaneously, mice in the TNBS-KE group were gavaged with the anti-inflammatory drug R-1,3-butanediol (R-1,3-butanediol) at the same concentration and dosage as in Example 1. The control and TNBS groups were gavaged with an equal volume of normal saline. After gavage, the mice were fed and weighed as normal.

[0088] (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 mixing 5% TNBS solution with anhydrous ethanol at a volume ratio of 1:1. The control group was treated with 50% ethanol solution prepared by mixing normal saline with anhydrous ethanol at a volume ratio of 1:1.

[0089] Before enema administration, stimulate the mouse to defecate to facilitate subsequent enema administration. Assemble the enema apparatus, attach the enema catheter, syringe, and connector. Anesthetize the mouse using a gas anesthesia machine. Lift the mouse's tail. Lubricate the enema tube evenly with paraffin oil. Insert the tube into the mouse's anus and slowly and carefully insert it into the rectum and colon, avoiding intestinal damage. While inserting the tube, gently push the 2.5% TNBS solution into the mouse using a syringe to avoid irritating the mouse or causing the liquid to overflow. Remove the tube after 4 cm of entry. Each mouse in the TNBS and TNBS-KE groups receives 100 µL of enema solution, while mice in the control group receive an equal volume of 50% ethanol solution. After the procedure, invert the anesthetized mouse for 1 minute to prevent liquid leakage. The mouse is then returned to its cage and allowed to recover.

[0090] 1.3 Experimental Animal Tissue Sample Preparation and Scoring Criteria

[0091] 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 TNBS colitis inflammation-related histological scoring system in Table 3.

[0092] Table 3 TNBS colitis inflammation-related histological scoring system

[0093]

[0094] 1.4 Experimental Results

[0095] Effects of R-1,3-butanediol on acute TNBS colitis in mice.

[0096] 2,4,6-Trinitrobenzenesulfonic acid (TNBS) can cause Crohn's disease-like colitis in mice, manifested by bloody stools, weight loss, shortened colon length, increased disease activity score, increased histopathological score, mucosal barrier destruction and inflammatory cell infiltration.

[0097] See also Figure 8 and Figure 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 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.

[0098] See also Figure 10 and Figure 11The 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.

[0099] See also Figure 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 drug can prevent and improve the diarrhea and bloody stool symptoms of mice with acute TNBS colitis.

[0100] See also Figure 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.

[0101] See also Figure 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.

[0102] 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.

[0103] Example 3

[0104] Effects of HMGCS2 gene knockout and R-1,3-butanediol supplementation on colitis in DSS mice

[0105] 1 Experimental methods

[0106] 1.1 Experimental Animal Grouping

[0107] 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).

[0108] 1.2 Experimental animal model establishment and drug administration

[0109] Same as Example 1.

[0110] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria

[0111] Same as Example 1.

[0112] 1.4 Experimental Results

[0113] Effects of HMGCS2 gene knockout and R-1,3-butanediol anti-inflammatory drug supplementation on colitis in DSS mice.

[0114] See also Figure 15 and Figure 16 The weight of mice in all three groups decreased, but 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 recovery of weight in HMGCS2 gene knockout mice.

[0115] See also Figure 17 The colon length of mice in the KO-DSS-KE group was about 0.8 cm longer on average than that in the KO-DSS 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.

[0116] See also Figure 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 on average 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 DAI score of HMGCS2 gene knockout mice and prevent and improve the diarrhea and bloody stool symptoms of HMGCS2 gene knockout mice.

[0117] See also Figure 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.

[0118] It can be seen that HMGCS2 intestinal epithelium-specific knockout mice are more sensitive to DSS than their 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.

[0119] Example 4

[0120] Effects of HMGCS2 gene knockout and R-1,3-butanediol supplementation on colitis in TNBS mice

[0121] 1 Experimental methods

[0122] 1.1 Experimental Animal Grouping

[0123] 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 HMGCS2 gene knockout mouse TNBS model group intervened by R-1,3-butanediol therapeutic agent (i.e., KO-TNBS-KE group).

[0124] 1.2 Experimental animal model establishment and drug administration

[0125] Same as Example 2.

[0126] 1.3 Observation content, experimental animal tissue sample preparation and scoring criteria

[0127] Same as Example 2.

[0128] 1.4 Experimental Results

[0129] Effects of HMGCS2 gene knockout and R-1,3-butanediol therapeutic supplementation on colitis in TNBS mice.

[0130] See also Figure 20 and Figure 21 The weight of the three groups of mice showed an overall downward trend. However, starting from the third day, the weight of the mice in the KO-TNBS-KE group began to increase, and on the fourth day, the weight increased to the same level as that of the mice in the WT-TNBS group. In other words, exogenous supplementation with the anti-inflammatory drug R-1,3-butanediol can slow down the further weight loss of TNBS colitis mice caused by HMGCS2 gene knockout and promote the recovery of weight in HMGCS2 gene knockout mice.

[0131] See also Figure 22 The 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.

[0132] See also Figure 23The 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.

[0133] See also Figure 24 The three groups of mice were scored using the TNBS colitis inflammation-related histological scoring system in Table 3. The average TNBS colon inflammation-related histological 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 histological score of HMGCS2 gene knockout mice.

[0134] 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 pathology score caused by HMGCS2 deficiency.

[0135] 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 non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. Use of R-1,3-butanediol in the preparation of a drug for preventing or treating inflammatory bowel disease, characterized in that: The drug for preventing or treating inflammatory bowel disease is a mixture of R-1,3-butanediol and physiological saline.

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