New Uses of Oleylethanolamine

Abstract

This invention belongs to the field of biomedical technology, specifically disclosing the application of oleylethanolamine in the preparation of drugs for preventing and treating intestinal radiation damage, and a drug for preventing and treating intestinal radiation damage. This invention utilizes a small intestinal organoid model and employs high-content screening technology to screen for oleylethanolamine, which can resist radiation damage to intestinal organoids, promote post-radiation regeneration and repair of organoids, promote stem cell proliferation and regeneration, improve post-irradiation survival rate, and alleviate morphological changes in the intestine caused by radiation damage. When oleylethanolamine is prepared into a drug and administered, it can improve intestinal lesions caused by radiation damage, protect stem cells from post-damage regeneration and repair, restore the self-renewal and differentiation functions of stem cells, enable stem cells to self-renew and replenish new stem cells, and differentiate into different types of epithelial cells to protect villous structures, thereby alleviating intestinal damage symptoms.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of oleoylethanolamine in the preparation of drugs for preventing and treating intestinal radiation damage, and a drug for preventing and treating intestinal radiation damage. Background Technology

[0002] The intestines, as the most important digestive organ in the human body, play a vital role not only in food digestion and nutrient absorption but also as a crucial barrier against the external environment. The crypt-villi structure is the basic structural unit of the intestine, with the exception of the large intestine and colon, which lack villi. Morphologically, the intestine consists of the innermost mucosa (epithelial layer), submucosa, muscularis propria, and the outer serosa. Anatomically, the segment of the intestine from the stomach to the anus is composed of the small intestine and the large intestine.

[0003] The intestine has a complete structure where stem cells self-renew and differentiate into different types of epithelial cells. These epithelial cells perform their secretory and absorptive functions, acting as a protective barrier for the intestine. The intestinal epithelium is generally renewed every 3-5 days, maintaining its inherent tissue state. The mesenchymal structure protects various cells, thus ensuring the integrity of the intestinal structure and function. Intestinal stem cells are distributed at the base of the crypts; the generation of new cells is achieved through the continuous proliferation and differentiation of these stem cells.

[0004] In 1974, crypt-based columnar cells (CBCs) adjacent to Paneth cells at the base of the crypts were first reported as intestinal stem cells. Hazel Cheng et al. discovered that intestinal stem cells can self-renew and differentiate into four other types of intestinal epithelial cells. Intestinal stem cells are located at the base of the crypts, adjacent to Paneth cells. Signaling pathways involving WNT, R-spondin, Notch, EGF, and BMP maintain the balance between self-renewal and differentiation of intestinal stem cells. Subsequently, Bjerknes, Cheng et al. further confirmed the function of CBCs as intestinal stem cells using genetic pedigree tracing. In 2007, Barker et al. used linked alleles to verify that Lgr5 is a specific marker for colonic and small intestinal stem cells. Following this, scientists successively verified that Lgr5-positive intestinal cells possess stem cell capabilities. In 2009, Hans Clevers' laboratory cultured 3D spheroids from mouse Lgr5+ stem cells in vitro, establishing the earliest protocol for epithelial tissue derived from individual intestinal stem cells. These so-called "organoids" or "mini-guts" can mimic the villi-like structure of the intestinal crypts in the body, and immunofluorescence staining can reveal that a single organoid contains all types of intestinal cells.

[0005] Organoids are collections of organ-specific cells that develop from stem cells or organ progenitor cells and can self-assemble through cell sequencing and spatially restricted lineage differentiation in a manner similar to that in vivo. Resembling real organs, organoids are miniaturized in vitro organ models. These models are formed by the self-organization of normal stem cells or tumor stem cells extracted from tumors or adjacent non-cancerous tissues in a specific 3D in vitro microenvironment, highly mimicking the characteristics of real organs in vivo. Because organoids possess physiological characteristics similar to those in vivo and can simulate the genetic and epigenetic features of target tissues or organs, they have significant application value in drug screening, precision medicine, organ development, and regenerative medicine.

[0006] Studies have found that exposure to high doses of radiation can cause acute radiation syndrome, including damage to the hematopoietic and gastrointestinal tracts. Gastrointestinal syndrome is a major cause of death from lethal radiation damage. Gastrointestinal syndrome can lead to vomiting, diarrhea, intestinal immune disorders, inflammation, intestinal flora imbalance, and even death. Radiation damage to the intestines can cause changes in intestinal crypt depth, villus length, and damage to intestinal epithelial cells. These changes are primarily due to the dysfunction of Lgr5+ intestinal stem cells, which cannot renew and regenerate in a timely manner, leading to apoptosis or death of epithelial cells. Developing drugs to combat intestinal radiation damage can promote the proliferation and regeneration of intestinal stem cells after radiation injury, accelerate the renewal of intestinal stem cells, and repair the intestinal protective barrier, thus alleviating radiation-induced diseases and even reducing mortality.

[0007] Using intestinal organoid models for screening compounds or drugs that combat radiation damage allows for the evaluation and preliminary screening of such compounds under conditions closely resembling the in vivo physiological environment. Organoids, being 3D cell cultures, contain organ-specific cell types and can represent the spatial organization of organs and replicate certain functions. 3D cultured organoids contain a wide variety of cells, going beyond simple cell-to-cell contact or adhesion, thus better simulating the development and state of organs and tissues. High-content screening (HCS) utilizes high-content imaging and analysis systems to perform multi-target analysis at the cell level. It rapidly, batch-wise, and automatically captures images of cells, subcellular structures, or tissues using automated cell imaging systems. Integrating bioinformatics, it quantitatively analyzes the phenotype of cell populations, converting cell images into numerical data, and achieving automated extraction and analysis of high-throughput image information.

[0008] Therefore, small intestinal organoid models can be used to screen for drugs that can promote organoid regeneration and repair after radiation and promote stem cell proliferation and regeneration using high-content screening technology. Summary of the Invention

[0009] The main technical problem addressed by this invention is to provide a drug capable of preventing and treating intestinal radiation damage, and the application of oleylethanolamine in the preparation of such drugs. This invention utilizes a small intestinal organoid model and employs high-content screening technology to screen for oleylethanolamine, which can resist radiation damage to intestinal organoids, promote post-radiation regeneration and repair of organoids, promote stem cell proliferation and regeneration, improve post-irradiation survival rate, and alleviate morphological changes in the intestine caused by radiation damage.

[0010] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0011] A novel use of oleoyl ethanolamide: its application in the preparation of drugs for the prevention and treatment of intestinal radiation damage. (Oleoyl ethanolamide, C...) 20 H 39 The chemical structural formula of NO2 is as follows:

[0012]

[0013] As a preferred embodiment of the present invention, the application is: the use of oleoylethanolamine in the preparation of a drug to resist intestinal radiation damage.

[0014] As a preferred embodiment of the present invention, the application includes, but is not limited to, one or more of the following:

[0015] (1) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate after intestinal radiation;

[0016] (2) Application of oleoylethanolamine in the preparation of drugs that promote intestinal regeneration and repair after radiation;

[0017] (3) Application of oleoylethanolamine in the preparation of drugs that promote the proliferation and regeneration of intestinal stem cells after intestinal radiation;

[0018] (4) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate of individuals after abdominal radiation;

[0019] (5) Application of oleoylethanolamine in the preparation of drugs that improve the morphological changes of villous-crypt structure after abdominal irradiation.

[0020] A drug for preventing intestinal radiation damage, wherein the active ingredient of the drug includes oleoylethanolamine.

[0021] In a preferred embodiment of the present invention, the content of oleoylethanolamine in the drug is a pharmacodynamic amount, such as 0.01%-99.99%.

[0022] As a preferred embodiment of the present invention, the drug further includes a pharmaceutically acceptable carrier, including but not limited to excipients, preservatives, stabilizers, wetting agents, emulsifiers, salts for adjusting osmotic pressure, buffers, etc.

[0023] In a preferred embodiment of the present invention, the dosage form of the drug is a pharmaceutically acceptable dosage form, including but not limited to powder for injection, injection solution, tablet, pill, capsule, spray, dispersion, etc.

[0024] As a preferred embodiment of the present invention, the route of administration of the drug is pharmaceutically acceptable, including but not limited to oral, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and transdermal, intranasal, or oral inhalation.

[0025] In a preferred embodiment of the present invention, the dosage of the drug is a pharmaceutically acceptable dosage.

[0026] The beneficial effects of this invention are:

[0027] This invention provides a drug for preventing and treating intestinal radiation damage, specifically the application of oleylethanolamine in the preparation of drugs for preventing and treating intestinal radiation damage. This invention utilizes a radiation damage model constructed from small intestinal organoids for drug screening, discovering that the compound oleylethanolamine can significantly improve the survival rate, budding rate, and organoid size changes caused by radiation damage, and can eliminate the adverse effects of intestinal radiation damage. After organoid irradiation, administration of oleylethanolamine significantly improved the survival rate and budding rate of organoids, and increased the organoid area compared to the control group. In experimental mice, intraperitoneal injection of oleylethanolamine after abdominal radiation damage significantly increased intestinal length and survival rate. HE staining of small intestinal sections showed improvements in crypt depth and villous structure, as well as increased crypt proliferation and stem cell number. These findings indicate that oleylethanolamine can improve intestinal lesions caused by radiation damage, protect stem cells from regeneration and repair after injury, restore the self-renewal and differentiation functions of stem cells, and enable stem cells to self-renew and replenish new stem cells, thereby differentiating into different types of epithelial cells to protect villous structures and alleviate intestinal damage symptoms. Attached Figure Description

[0028] Figure 1 The figure shows the effect of different concentrations of oleoylethanolamine on the repair and growth of irradiated organoids.

[0029] Figure 2 The figure shows the experimental results of the protective effect of oleoylethanolamine on the repair of radiation damage in mice.

[0030] To more clearly illustrate the technical solutions protected by this invention, the accompanying drawings in the embodiments and / or experimental examples have been briefly described above. It should be understood that the above drawings should not be considered as any limitation on the scope of protection of this invention. For those skilled in the art, other related drawings can be derived from these drawings without any inventive effort. Detailed Implementation

[0031] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments and experimental examples. Those skilled in the art should understand that the following embodiments and experimental examples are only used to illustrate the technical solution and technical effects of the present invention and should not be considered as any limitation on the scope of protection of the present invention. Based on the following embodiments, other technical solutions obtained by those skilled in the art without creative effort, such as technical solutions obtained through modifications, variations, or simple substitutions, are all within the scope of protection of the present invention.

[0032] Example 1

[0033] This embodiment provides a new use for oleylethanolamine, specifically: the application of oleylethanolamine in the preparation of drugs for preventing and treating intestinal radiation damage.

[0034] Example 2

[0035] This embodiment provides the application of oleoylethanolamine in the preparation of a drug to resist intestinal radiation damage, including one or more of the following;

[0036] (1) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate after intestinal radiation;

[0037] (2) Application of oleoylethanolamine in the preparation of drugs that promote intestinal regeneration and repair after radiation;

[0038] (3) Application of oleoylethanolamine in the preparation of drugs that promote the proliferation and regeneration of intestinal stem cells after intestinal radiation;

[0039] (4) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate of individuals after abdominal radiation;

[0040] (5) Application of oleoylethanolamine in the preparation of drugs that improve the morphological changes of villous-crypt structure after abdominal irradiation.

[0041] Example 3

[0042] This embodiment provides a drug for preventing intestinal radiation damage, the active ingredient of which includes oleoylethanolamine, the content of which is a pharmacodynamic amount; it also includes a pharmaceutically acceptable oily solvent for preparing the drug into an injection solution.

[0043] In other embodiments of the invention, the drug may also include other pharmacodynamic ingredients and pharmaceutically acceptable carriers to facilitate formulation into other pharmaceutically acceptable dosage forms.

[0044] Experimental Example

[0045] I. Organoid Irradiation

[0046] Experimental methods:

[0047] 1. After the C57BL / 6J mice were sacrificed, a section of small intestine about 7cm (5-10cm is also acceptable) was taken under sterile conditions, and the mesentery and adipose tissue were removed with forceps.

[0048] 2. Using a syringe filled with sterile cold PBS (containing 1 / 1000 of the bispecific antibody, all cold PBS below contain bispecific antibodies), rinse the intestinal contents clean. Use tweezers again to remove as much mesentery and some fatty tissue as possible. Cut the intestine lengthwise and wash it in a clean disposable bacterial culture dish filled with cold PBS.

[0049] 3. Cut the intestine into segments of 0.5-1cm in length, transfer them to a 50mL centrifuge tube containing 30mL of sterile cold PBS, shake vigorously for 50 times (3 shakes / second on average), discard the supernatant, add another 30mL of cold PBS to the centrifuge tube, and repeat 5-7 times until the liquid is clear.

[0050] 4. Add 30 mL of 1 mM EDTA / cold PBS to the centrifuge tube and digest at 4°C for 30 min.

[0051] 5. Shake vigorously for 50 seconds, discard the supernatant, add 30 mL of 5 mM EDTA / cold PBS to the centrifuge tube, and digest at 4°C for 20 min.

[0052] 6. Gently shake the centrifuge tube up and down 4-5 times, discard the supernatant, and wash with cold PBS 2-3 times to remove EDTA.

[0053] 7. Add 30 mL of cold PBS containing 1% serum to the centrifuge tube, vortex the centrifuge tube for 30 seconds, and filter the supernatant through a 70 μm filter. This is fraction 1. At this point, the crypts are already present in the supernatant.

[0054] 8. Add about 30 mL of cold PBS to the centrifuge tube again, vortex for 30 seconds, and filter the supernatant through a 70 μm filter. This is fraction 2.

[0055] 9. Centrifuge fraction 2 at 300g, 4℃, for 3 min, discard the supernatant, add an appropriate amount of cold PBS to make up the volume, take 10μL, count under a microscope, and calculate the number of crypts.

[0056] 10. Thaw Matrigel on ice in advance, and preheat the 96-well plate in a 37°C incubator.

[0057] 11. Take the required number of crypts (about 20 crypts per well), centrifuge at 300g, 4℃, for 3 min, discard the supernatant, resuspend in PBS and Matrigel (PBS: Matrigel = 1:1), mix well, and spread in a 96-well plate, 5 μL / 20 crypts / well, incubate at 37℃ for 10-15 min, and after Matrigel solidifies, add 80 μL of culture medium to each well.

[0058] 12. The planted organoids were randomly divided into an irradiated untreated (Vehicle) group and an irradiated treated (OEA) group, with 3 wells in each group. When the organoids grew to the point of just sprouting (2-3 days), they were irradiated with an X-ray biological irradiator at a dose of 6 Gy, 0.93 Gy / min.

[0059] 13. 24 hours after irradiation (IR), the irradiated drug administration group was treated with different concentrations of oleoyl ethanolamide (OEA) of 100 nM, 500 nM, 2 μM and 8 μM, and the vehicle group was treated with the same volume of DMSO. The culture medium was changed every 3 days.

[0060] 14. Before irradiation, the number of organoids was counted and recorded. The day of irradiation was designated as Day 0. On Day 5, the survival rate of organoids was recorded. On Day 9, the germination rate and surface area of ​​organoids were recorded. The experimental results are as follows: Figure 1 As shown.

[0061] Experimental results:

[0062] like Figure 1As shown, Figure A presents a typical image of organoids on day 9 after irradiation with different concentrations of oleylethanolamine, and Figure B shows the statistical results of organoid survival rate on day 5 after irradiation with different concentrations of oleylethanolamine. Compared with the Vehicle group, the experimental group showed improved organoid survival status and survival rate, with 2 μM being the optimal treatment concentration. Specifically, the average survival rate of organoids in the Vehicle group was 31.67%, the average survival rate in the 100 nM oleylethanolamine treatment group was 56.96%, the average survival rate in the 500 nM oleylethanolamine treatment group was 60.87%, the average survival rate in the 2 μM oleylethanolamine treatment group was 70.60%, and the average survival rate in the 8 μM oleylethanolamine treatment group was 52.54%. The results indicate that 2 μM is the optimal concentration. Figure C shows a schematic diagram of the growth of organoids after irradiation with 2 μM oleylethanolamine and the Vehicle group. Figure D shows typical budding rates of organoids on day 9 in the Vehicle group and the 2 μM oleoylethanolamine treatment group. It can be seen that the budding rate of organoids in the 2 μM oleoylethanolamine treatment group was significantly improved. Figures E and F show the budding rate statistics and organoid surface area statistics. The results show that the average number of buds in the Vehicle group was 1.67, while the average number of buds in the 2 μM oleoylethanolamine treatment group was 5.54; the average surface area of ​​the Vehicle group organoids was 6.5 × 10⁻⁶. 4 μm 2 The average surface area of ​​organoids in the 2 μM oleoylethanolamine treatment group was 12.3 × 10⁻⁶. 4 μm 2 .

[0063] II. Mouse Irradiation

[0064] Experimental methods:

[0065] 1. Thirty-nine female C57BL / 6J mice, weighing 20-22g, were randomly divided into three groups: normal group (WT), irradiated and untreated group (Vehicle), and oleoylethanolamine treated group (OEA). The variables for the three groups were whether they were irradiated and whether they were treated. There were 13 mice in each group.

[0066] 2. Inject 280-300 μL of tribromoethanol anesthetic into the mouse intraperitoneally to anesthetize the mouse. Cover the head and neck with lead plates, leaving only about 2.5 cm of the abdomen exposed. Irradiate the mouse abdomen with an X-ray biological irradiation device using an irradiation dose of 14 Gy.

[0067] 3. The day of irradiation is counted as Day 0. 24 hours after irradiation, each mouse in the oleoylethanolamine (OEA) group was injected intraperitoneally with 20 mg / kg oleoylethanolamine / 100 μL corn oil daily. The normal (WT) group and the irradiated vehicle group were injected intraperitoneally with the same dose of DMSO / 100 μL corn oil. The administration was carried out for 4 consecutive days, and the survival rate of the mice was counted for 14 consecutive days.

[0068] 4. On the 4th day after irradiation, 3 mice were randomly selected from each group, dissected, intestines were taken, and intestinal length was counted. The small intestine was fixed with 4% PFA and sent to the company for paraffin embedding.

[0069] 5. Prepare paraffin sections, perform HE staining, observe the morphology of the small intestinal epithelium, as well as the depth of crypts and the length of villi, and statistically analyze them. The specific procedure is as follows: Place the paraffin sections in xylene I and II for 10 min each, then in anhydrous ethanol I and II, 95% ethanol, 80% ethanol, 70% ethanol, and 50% ethanol for 5 min each for gradient dewaxing; wash in water, wipe off the moisture, stain with hematoxylin for 2 min, rinse with running water, stain with eosin for 2 min, rinse with running water, then place the paraffin sections in 50% ethanol for 2 min, 70% ethanol for 2 min, 80% ethanol for 2 min, 95% ethanol for 5 min, anhydrous ethanol for 5 min, and xylene for 5 min for clearing. Afterward, remove the sections from the xylene and mount them with neutral resin.

[0070] 6. Immunofluorescence staining of paraffin sections: After dewaxing the small intestine paraffin sections as in the previous step, incubate them in a boiling water bath with EDTA antigen retrieval solution for 20 min, then allow them to cool naturally. Permeabilize with 0.2% Triton X-100 (prepared in PBS) for 20 min, then block with 0.01% Triton X-100 (prepared in PBS) containing 10% goat serum for 30 min. Incubate overnight at 4°C with diluted OLFM4 (Olfactomedin 4, an intestinal stem cell marker) primary antibody. Wash with PBS (5 min × 3 times). Incubate with diluted secondary antibody containing Cy5 fluorescent labeling and DAPI at room temperature for 1 h. Wash with PBS (5 min × 3 times). Mount with cedarwood oil and perform a full scan using an intelligent pathological imaging analysis system. Use the same method to stain the small intestine paraffin sections with Ki67 to indicate intestinal proliferation. Experimental results are as follows: Figure 2 As shown.

[0071] Experimental results:

[0072] like Figure 2As shown in Figure A, which is the flowchart of the mouse experiment, the day of irradiation is designated as Day 0. 24 hours after irradiation, mice were intraperitoneally injected with oleylethanolamine at a dose of 20 mg / kg for four consecutive days. On days 4 and 5, three mice from each group were randomly selected and sacrificed, and their small intestines were photographed and statistically analyzed, as shown in Figure B. The average small intestine length was 32.17 cm in the normal (WT) group, 16 cm in the untreated (Vehicle) group, and 20.53 cm in the oleylethanolamine (OEA) group. Figure C shows the survival rates of mice in the untreated (Vehicle) and oleylethanolamine (OEA) groups. On day 14 after irradiation, the survival rate of mice in the untreated (Vehicle) group was 0%, while the survival rate of mice in the oleylethanolamine (OEA) group was 40%. Figure D shows the HE staining results, and Figures E and F show the statistical results of villus length and crypt depth in the small intestine. It can be seen that intraperitoneal injection of oleoylethanolamine can improve the morphology of the small intestine in mice. In the vehicle group, due to radiation damage, the villi are shorter, the crypt depth is reduced, the villus-crypt structure is damaged, villi are lost in severe areas, and the crypt morphology is changed. In contrast, the villus and crypt morphology of the small intestine in the oleoylethanolamine (OEA) group are improved. Specifically, the average villus length in the small intestine of mice in the vehicle group was 261.20 μm, while that in the OEA group was 369.74 μm; the average crypt depth in the small intestine of mice in the vehicle group was 53.16 μm, while that in the OEA group was 79.77 μm. Figure G is a typical image of immunofluorescence staining of small intestinal paraffin sections for intestinal stem cells Olfm4. Figure H is a statistical graph, which shows that the proportion of Olfm4+ cells per crypt in the small intestine of mice in the untreated (Vehicle) group is significantly lower than that in the oleoylethanolamine (OEA) group. Specifically, the average number of Olfm4+ cells per crypt in the small intestine of mice in the untreated (Vehicle) group is 5.2, while the average number of Olfm4+ cells per crypt in the small intestine of mice in the oleoylethanolamine (OEA) group is 7.43. Figure I shows a typical immunofluorescence staining of Ki67 cells in a paraffin section of the small intestine. Figure J is a statistical graph, which shows that the proportion of Ki67+ cells per crypt in the small intestine of mice in the untreated (Vehicle) group was significantly lower than that in the oleoylethanolamine (OEA) group. Specifically, the average number of Ki67+ cells per crypt in the small intestine of mice in the untreated (Vehicle) group was 11.93, while the average number of Ki67+ cells per crypt in the small intestine of mice in the OEA group was 17.93. This indicates that oleoylethanolamine can reduce the damage to stem cells in the mouse small intestine caused by radiation, increase the number of stem cells, and promote their proliferation and regeneration.

[0073] III. Experimental Conclusions

[0074] The intestine is one of the radiation-sensitive target organs, with the small intestine being the most sensitive, especially the small intestinal crypt stem cells, which are highly sensitive to radiation. Radiation damage to the intestine weakens or even eliminates the intestinal mucosal barrier function, reducing its protective function and causing a series of diseases such as nausea, vomiting, diarrhea, and gastrointestinal bleeding. From a biological perspective, radiation damage to the intestine impairs the intestinal mucosal barrier, damages intestinal stem cell function, and impairs the intestine's self-renewal and differentiation functions. Epithelial cells are not replenished in time, and the crypt-villi structure changes, leading to villi loss and other pathological changes. Cultured intestinal organoids can highly simulate the morphological and growth differentiation changes of the intestine under the physiological microenvironment in vivo. This invention utilizes a small intestinal organoid model and employs high-content screening technology to screen for oleoylethanolamine, which can resist radiation damage to intestinal organoids, promote radiation regeneration of organoids, and promote the proliferation and regeneration of stem cells. It also improves the survival rate of mice after abdominal irradiation and alleviates morphological changes in the mouse intestine caused by radiation damage. In other words, oleoylethanolamine can improve intestinal lesions caused by radiation damage, protect stem cells from regeneration and repair after damage, restore the self-renewal and differentiation functions of stem cells, enable stem cells to self-renew and replenish stem cells, and differentiate into different types of epithelial cells to protect villous structures, thereby alleviating intestinal damage symptoms.

[0075] Although the technical solutions and effects of the present invention have been described in detail above with general descriptions, specific embodiments and experimental examples, any modifications, substitutions or improvements made by those skilled in the art without departing from the spirit and scope of the present invention shall fall within the protection scope of the present invention.

Claims

1. A novel application of oleoylethanolamine, characterized by: The application is as follows: the use of oleoylethanolamine in the preparation of drugs for preventing and treating intestinal radiation damage; The active ingredient of the drug is oleoylethanolamine; The content of oleoylethanolamine in the drug is the effective dose.

2. The novel application according to claim 1, characterized in that: The application is: the use of oleoylethanolamine in the preparation of drugs that resist intestinal radiation damage.

3. The novel application according to claim 1, characterized in that: The applications include one or more of the following: (1) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate after intestinal radiation; (2) Application of oleoylethanolamine in the preparation of drugs that promote intestinal regeneration and repair after radiation; (3) Application of oleoylethanolamine in the preparation of drugs that promote the proliferation and regeneration of intestinal stem cells after intestinal radiation; (4) Application of oleoylethanolamine in the preparation of drugs that improve the survival rate of individuals after abdominal radiation; (5) Application of oleoylethanolamine in the preparation of drugs that improve the morphological changes of villous-crypt structure after abdominal irradiation.

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