Application of D-mannose in preparation of medicine for preventing, relieving or treating intestinal injury diseases caused by ionizing radiation

Abstract

The invention relates to the technical field of medicines, in particular to application of D-mannose in preparation of medicines for preventing, relieving or treating intestinal injury diseases caused by ionizing radiation. It is found for the first time that D-mannose can effectively relieve intestinal injury caused by ionizing radiation and does not reduce the radiosensitivity of tumor cells, can serve as a main active component to prepare drugs, and is applied to intestinal injury diseases caused by ionizing radiation, such as intestinal villus injury, intestinal barrier damage and intestinal epithelium regeneration capacity reduction, caused by radiation. The invention develops new application of D-mannose, overcomes the possible strong toxic and side effects of radiation protection drugs and the limitation of tumor protection, provides a new therapeutic scheme for radioactive intestinal injury of organisms, and has wide application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to application of D-mannose in preparing medicines for preventing, alleviating or treating intestinal damage diseases caused by ionizing radiation. Background Art

[0002] Radiation injury, also known as radiation enteropathy, is the most common and most serious complication after radiotherapy for abdominal and pelvic tumors. Statistics show that almost all patients undergoing radiotherapy for abdominal and pelvic tumors will experience obvious gastrointestinal symptoms, of which 15%-20% of patients have severe symptoms and need to change their treatment plans. Radiation enteropathy is still the most important limiting factor for current radiotherapy doses. In addition, the widespread application of nuclear technology in the fields of energy and medicine has provided important guarantees for national energy security and national health. At the same time, however, nuclear power plant accidents have occurred many times internationally, and the widespread use of medical radiation devices may also lead to medical accidents, all of which may cause radiation enteropathy.

[0003] Radiation intestinal injury can be divided into two stages: acute radiation enteritis occurs within a few days after radiotherapy, mainly due to the mutual promotion of mucosal barrier destruction caused by insufficient intestinal epithelial renewal and cascade-amplified inflammation, clinically manifested as nausea, abdominal pain, diarrhea and infection, and in severe cases can lead to septic shock; chronic (delayed) enteritis occurs several months to years after radiation exposure, and its pathological characteristics are irreversible intestinal villous atrophy, intestinal wall fibrosis and microvascular sclerosis, clinically manifested as malnutrition, chronic diarrhea, and may progress to intestinal obstruction and intestinal perforation. At present, the treatment of radiation intestinal injury is mainly symptomatic, including the use of hemostatic drugs, antibiotics, steroid drugs, intestinal mucosal protective agents, probiotics, parenteral nutrition support, etc. to control intestinal symptoms, etc. Complications caused by delayed enteritis such as obstruction, bleeding, perforation, stenosis, ulcers, etc. are mainly solved through surgery. Amifostine (WR2721) is currently the only specific drug approved for reducing radiation damage. However, due to its serious adverse reactions (nausea, vomiting, hypotension, etc.) and narrow therapeutic window, it is only approved for use in patients with head and neck cancer undergoing radiotherapy to reduce the incidence of moderate to severe dry mouth symptoms, and has not been approved for radiation-induced intestinal injury. In short, there are currently no specific preventive and therapeutic drugs for radiation-induced intestinal injury in clinical practice. Some treatment methods are insufficiently based on evidence and lack effective and reliable standardized treatment plans. The intestinal radiation damage protective agents under development focus on promoting DNA damage repair or reducing oxidative stress levels. They are not very specific and may also protect tumor cells. In addition, there are problems such as large side effects and high prices. The prospects for new drug development are still unclear. With the improvement of cancer diagnosis and treatment, the survival time of patients has been prolonged, and the number of cancer survivors has increased significantly. The importance of reducing the side effects of radiotherapy and improving the quality of life of patients has become increasingly prominent. Therefore, it is of great significance to find drugs to prevent and treat radiation enteritis.

[0004] Mannose (C6H 12 O6), is a monosaccharide (hexose) with a structure similar to glucose. D-mannose and L-mannose are chiral compounds. They are two different stereoisomers of mannose. D-mannose is abundant in nature, in different types of fruits, and widely distributed in human body fluids and tissues, while L-mannose is relatively rare in nature and is usually found in the polysaccharides of certain bacteria. Unlike glucose, mannose is not widely metabolized in the human body to produce energy after oral ingestion. The main physiological function of mannose is to participate in the glycosylation modification of proteins as a key metabolic substrate for glycosylation. Mannose is poorly absorbed orally, and more than 90% is excreted through urine. Clinically, it has been shown to have a satisfactory therapeutic effect on urinary tract infections. Recent studies have also found that mannose can promote immune tolerance and inhibit the development of inflammatory diseases related to autoimmunity and allergies. More importantly, it has also been found that mannose effectively inhibits tumors by inhibiting glycolysis and enhancing the effects of chemotherapeutic drugs. Although the application of D-mannose has been widely studied, there are no reports on whether it can alleviate radiation-induced intestinal injury. Summary of the invention

[0005] The present invention discovers and confirms for the first time that D-mannose can effectively reduce intestinal damage caused by ionizing radiation without reducing the radiation sensitivity of tumor cells.

[0006] Based on this, the present invention first provides the use of D-mannose in preparing a medicine; the medicine is used in at least one of the following aspects: (1) Prevent, alleviate or treat intestinal damage caused by ionizing radiation, intestinal villus damage, intestinal barrier destruction or decreased intestinal epithelial regeneration capacity; (2) Reduce the death of intestinal organoids caused by ionizing radiation; (3) Radioprotection of intestinal organoids.

[0007] Preferably, the intestinal damage disease caused by ionizing radiation is radiation enteritis.

[0008] Preferably, the radiation enteritis is caused by radiotherapy of pelvic malignancies and / or abdominal malignancies and / or retroperitoneal malignancies.

[0009] Preferably, the radiation enteritis is caused by a medical accident.

[0010] Preferably, the radiation enteritis is caused by a nuclear accident.

[0011] Preferably, the drug comprises D-mannose and pharmaceutically acceptable excipients.

[0012] Preferably, the dosage form of the drug is a solid preparation or a liquid preparation.

[0013] Preferably, the solid preparation is a powder, granule, capsule or tablet, and the liquid preparation is an oral solution or injection.

[0014] In the application of the present invention, the drug will not reduce the radiation sensitivity of intestinal tumor cells.

[0015] In the application of the present invention, the drug achieves its application purpose through at least one of the following approaches: (1) Promote the regeneration of small intestinal crypts after irradiation; (2) Inhibit irradiation-induced apoptosis of small intestinal crypt cells; (3) Promote the recovery of intestinal villi after irradiation; (4) Protecting the intestinal epithelial barrier; (5) Protect small intestinal stem and progenitor cells.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The present invention discovers for the first time that D-mannose can effectively reduce intestinal damage caused by ionizing radiation without reducing the radiation sensitivity of tumor cells. It can be used as the main active ingredient to prepare drugs, and is applied to intestinal damage diseases caused by ionizing radiation, such as intestinal villus damage, intestinal barrier destruction, and decreased intestinal epithelial regeneration ability. It opens up new uses for D-mannose, overcomes the limitations of radiation protection drugs such as strong toxic and side effects and tumor protection, provides a new treatment plan for radiation intestinal damage in organisms, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the result of D-mannose promoting the regeneration of small intestinal crypts after irradiation.

[0018] Figure 2 The result is that D-mannose inhibits the apoptosis of small intestinal crypt cells induced by irradiation.

[0019] Figure 3 The result is that D-mannose promotes the recovery of small intestinal villi after irradiation.

[0020] Figure 4 This is the result of D-mannose protecting the intestinal epithelial barrier.

[0021] Figure 5 The result is that D-mannose protects small intestinal stem and progenitor cells.

[0022] Figure 6 This is the result of the radioprotective effect of D-mannose on in vitro irradiated intestinal organoids.

[0023] Figure 7 The result is that D-mannose does not reduce the radiation sensitivity of colon tumor cells.

[0024] Figure 8 The result is that D-mannose does not reduce the sensitivity of colorectal tumors to radiotherapy. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] In the examples provided in this specification, if no specific techniques or conditions are specified, the techniques or conditions described in the literature in this field or the product instructions are used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased through regular channels.

[0027] Example 1D-Mannose promotes small intestinal crypt regeneration after irradiation 1.1 Experimental animals: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g.

[0028] 1.2 Experimental groups: The mice were divided into irradiation control group (IR) and D-mannose group (IR+Mannose), with 4 mice in each group.

[0029] 1.3 Administration method: D-mannose was dissolved in physiological saline and used immediately after preparation. Mice were given the drug three times at a dose of 100 mg / kg, 24 hours, 12 hours, and 2 hours before irradiation, by intraperitoneal injection.

[0030] 1.4 Experimental steps: (1) The drug-treated group was given drugs before irradiation, and the control group was given normal saline; (2) The recipient mice received whole-body X-ray irradiation with doses of 0 Gy, 10 Gy, 12 Gy, 14 Gy, and 16 Gy at a dose rate of 0.72 Gy / min; (3) 5-fluorouracil (BrdU) was intraperitoneally administered at 120 mg / kg 2 hours before sampling. The sampling time point was 3.5 days after irradiation. The small intestine jejunum segment was obtained and fixed with formaldehyde; (4) Prepare paraffin sections of intestinal tissue with a thickness of 4 μm; (5) Dewaxed paraffin sections of intestinal tissue were then stained with BrdU immunohistochemistry. The number of regenerated crypts in the complete intestinal loops was counted under a microscope. Five intestinal loops were counted for each mouse.

[0031] 1.5 Experimental results: like Figure 1As shown, the number of small intestinal crypts in irradiated mice decreased significantly with the increase of irradiation dose. The number of crypts in non-irradiated control mice was (140.2±5.57) / intestinal loop. After irradiation of 10Gy, 12Gy, 14Gy, and 16Gy, the number of crypts decreased to (97.95±7.47) / intestinal loop, (54.25±12.08) / intestinal loop, (28.6±8.79) / intestinal loop, and (19.95±7.93) / intestinal loop, respectively. After administration of mannose, there was no significant difference in the number of crypts before irradiation compared with the control. After irradiation of 10Gy-16Gy, the number of regenerated crypts increased significantly, which was 110%, 127%, 183%, and 125% of the control group.

[0032] Example 2 D-mannose inhibits irradiation-induced apoptosis of small intestinal crypt cells 2.1 Experimental animals: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g.

[0033] 2.2 Experimental groups: The mice were divided into irradiation control group (IR) and D-mannose group (IR+Mannose).

[0034] 2.3 Administration method: D-mannose was dissolved in physiological saline and used immediately after preparation. Mice were given the drug three times at a dose of 100 mg / kg by intraperitoneal injection, 24 hours, 12 hours, and 2 hours before irradiation.

[0035] 2.4 Experimental steps: (1) The drug-treated group was given drugs before irradiation, and the control group was given normal saline; (2) The recipient mice received whole-body X-ray irradiation with a dose of 14 Gy and a dose rate of 0.72 Gy / min; (3) 4 hours and 24 hours after irradiation, small intestine jejunum segments were obtained and fixed with formaldehyde; (4) Prepare paraffin sections of intestinal tissue with a thickness of 4 μm; (5) TUNEL kit was used to detect cell apoptosis in paraffin sections of intestinal tissue. Five intestinal loops were counted under a microscope for each mouse, and the number of apoptotic cells in five complete crypts in each intestinal loop was counted.

[0036] 2.5 Experimental results: like Figure 2 As shown, a large number of apoptotic cells appeared in the intestinal crypt cells of mice 4 hours and 24 hours after irradiation, mainly distributed in the rapid expansion area and the bottom of the crypt, which were (6.65±2.91) / crypt and (5.05±2.04) / crypt, respectively. The number of apoptotic cells in the mannose-treated group decreased by 23.59% and 24.56% at the above two time points, respectively, and the difference was statistically significant (p<0.0001).

[0037] Example 3 D-mannose promotes the recovery of small intestinal villi after irradiation 3.1 Experimental animals: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g.

[0038] 3.2 Experimental groups: divided into irradiation control group (IR) and mannose group (IR+Mannose).

[0039] 3.3 Administration method: D-mannose was dissolved in physiological saline and used immediately after preparation. Mice were given the drug three times at a dose of 100 mg / kg by intraperitoneal injection, 24 hours, 12 hours, and 2 hours before irradiation.

[0040] 3.4 Experimental steps: (1) The drug-treated group was given drugs before irradiation, and the control group was given normal saline; (2) The recipient mice received whole-body X-ray irradiation with a dose of 14 Gy and a dose rate of 0.72 Gy / min; (3) The time points for sampling mice were before irradiation and 24, 48, 84, and 120 hours after irradiation. The small intestine jejunum segments were obtained and fixed with formaldehyde. (4) Prepare paraffin sections of intestinal tissue with a thickness of 4 μm; (5) Measurement of intestinal villus length: paraffin sections of intestinal tissue were taken and stained with HE after dewaxing. The length of complete intestinal villi in the intestinal cavity was measured under a microscope. Five intestinal loops were counted for each mouse, and the length of five complete villi was counted for each intestinal loop.

[0041] 3.5 Experimental results: like Figure 3 As shown in the figure, the length of intestinal villi of mice in the IR group gradually shortened after irradiation, and the density of intestinal epithelial cells on the surface of the villi changed from dense to sparse. The quantitative results showed that the average length of the villi was (577.98±51.4) μm when not irradiated, and the average length of the villi was shortened to (551.28±78.15) μm, (529.23±101.52) μm, (468.31±81.32) μm, and (475.51±81.69) μm at 24, 48, 84, and 120 hours after irradiation, respectively. There was no significant difference between the villi length of the drug-treated group and the control before irradiation, but the degree of shortening of the villi length was significantly reduced after irradiation, which was 16.28%, 19.26%, 32.48%, and 49.56% of the corresponding time points of the control group, respectively.

[0042] Example 4 D-mannose protects the intestinal epithelial barrier 4.1 Experimental animals: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g.

[0043] 4.2 Experimental groups: The mice were divided into normal control group (Vehicle), simple drug administration group (Mannose), irradiation control group (IR) and mannose group (IR+Mannose).

[0044] 4.3 Administration method: Mannose was dissolved in physiological saline and used immediately after preparation. The recipient mice were given the drug three times at a dose of 100 mg / kg, 24 hours, 12 hours, and 2 hours before irradiation, by intraperitoneal injection.

[0045] 4.4 Experimental steps: (1) The drug-treated group was given drugs before irradiation, and the control group was given normal saline; (2) The recipient mice received whole-body X-ray irradiation with a dose of 14 Gy and a dose rate of 0.72 Gy / min; (3) On the fifth day after irradiation, mice were orally gavaged with FITC-dextran at a concentration of 44 mg / 100 g in a volume of 200 μL. Four hours after gavage, blood was collected from the heart, and the serum of the mice was collected. 50 μL of the diluted serum samples, standards, and blank controls (PBS and diluted serum from untreated mice) were transferred to a black 96-well microplate. The fluorescence intensity (excitation wavelength, 492 nm; emission wavelength, 525 nm) was measured using a microplate reader to calculate the FITC-dextran concentration.

[0046] 4.5 Experimental results: like Figure 4 As shown in the figure, the concentrations of FITC-dextran in the serum of the Vehicle group and the Mannose group were (4.42±0.84) and (5.00±1.06) μg / ml, respectively, with no significant difference (p=0.18). Four days after irradiation, intestinal permeability increased and the concentration of FITC-dextran increased to (14.13±2.34) μg / ml. Compared with the IR group, the concentration of FITC-dextran in the (IR+Mannose) group was (8.06±0.43) μg / ml, with a significant difference (p<0.0001).

[0047] Example 5 D-mannose protects small intestinal stem and progenitor cells 5.1 Experimental animals: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g.

[0048] 5.2 Experimental groups: The animals were divided into normal control group (Vehicle), simple drug administration group (Mannose), irradiation control group (IR), and irradiation combined with Mannose administration group (IR+Mannose).

[0049] 5.3 Administration method: Mannose was dissolved in physiological saline and used immediately after preparation. The recipient mice were given the drug three times, 24 hours, 12 hours, and 2 hours before irradiation. The dosage was 100 mg / kg, and the drug was administered by intraperitoneal injection.

[0050] 5.4 Experimental steps: (1) The drug-treated group was given drugs before irradiation, and the control group was given normal saline; (2) The recipient mice received whole-body X-ray irradiation with a dose of 14 Gy and a dose rate of 0.72 Gy / min; (3) Olfm4 immunohistochemical detection of intestinal stem cells: The small intestinal tissue was obtained 48 hours after irradiation, fixed with formaldehyde and then sliced ​​into paraffin with a thickness of 4 μm. The slices were dewaxed and then immunohistochemically labeled with Olfm4 for intestinal stem and progenitor cells. The number of Olfm4-positive cells in the intact crypts was counted under a microscope. Five intestinal loops were counted for each mouse, and five crypts were counted for each intestinal loop.

[0051] 5.5 Experimental results: like Figure 5 As shown, the average number of Olfm4-positive cells in each crypt of the Vehicle group and the Mannose group was (15.7±3.15) and (15.7±3.24), respectively, with no significant difference (p=1). Two days after irradiation, the number of Olfm4-positive cells in the IR group decreased to (3.18±1.42) / crypt, and the number of Olfm4-positive cells in the (IR+Mannose) group increased by 52.83% compared with the IR group, with a significant difference (p<0.0001).

[0052] Example 6 D-mannose has a radioprotective effect on in vitro irradiated intestinal organoids 6.1 Experimental animals and main reagents: C57BL / 6J mice, male, 6-8 weeks old, weighing 20-22 g, intestinal organoid culture medium (MethoCult GF M3434, Stemcell).

[0053] 6.2 Experimental groups: irradiation control group (IR) and mannose administration group (IR+Mannose).

[0054] 6.3 Experimental steps: (1) Obtaining small intestinal crypts: After killing the mice, 8-10 cm of jejunum were obtained under sterile conditions, and the extraintestinal mesentery, blood vessels, and fat were removed. After longitudinally cutting the intestine, the intestinal villi were gently scraped off, and the intestine was cut into segments of about 1 cm with a blade. The intestinal segments were washed with ice-cold DPBS for 6-8 times, and ice-cold 2mM EDTA / DPBS solution was added. Incubate on ice for 20 minutes, shake vigorously for 30 seconds, collect the liquid, filter with a 70μm filter, and observe the purity of the complete crypts under a microscope; (2) Small intestinal organoid culture: Centrifuge the prepared crypt solution at 150g for 3 min at 4°C, discard the supernatant, resuspend the precipitate in pre-cooled DMEM / F-12 for counting, dilute to an appropriate concentration for inoculation, mix with the prepared matrix gel at a ratio of 1:1, and then inoculate 50 μL / well into a 24-well plate. Add 100 μL of organoid culture medium and culture at 37°C with 5% CO2. Observe the growth of the organoids daily. (3) After organoids grew stably, they were passaged, randomly divided into groups, and administered mannose at a dose of 20 mM; (4) The grouped organoids were irradiated with 12 Gy of X-rays at a dose rate of approximately 72 cGy / min; (5) Eight days after irradiation, record the organoid survival rate, number of buds, and average surface area.

[0055] 6.4 Experimental Results like Figure 6 As shown, the survival rate, number of buds and surface area of ​​organoids decreased significantly after irradiation. After mannose administration, the survival rate, number of buds and surface area increased by 20.45%, 65.78% and 54.23%, respectively, and the difference was statistically significant.

[0056] Example 7 D-mannose does not reduce the radiation sensitivity of colon tumor cells 7.1 Experimental cells: mouse colon cancer cell line (CT-26), human colon adenocarcinoma cell line (HT-29), and human colon adenocarcinoma cell line (RKO).

[0057] 7.2 Experimental groups: divided into control group (CTR), simple drug administration group (Mannose), irradiation control group (IR) and irradiation drug administration group (IR+Mannose).

[0058] 7.3 Experimental steps: (1) Plate tumor cells in a 96-well plate, 1000 cells / well; (2) After the cells adhered, mannose with a final concentration of 20 mM was added to the drug group, and physiological saline was added to the CTR and IR groups; (3) 2 hours after administration, cells were irradiated with 12 Gy of X-rays at a dose rate of approximately 72 cGy / min; (4) Use the CCK8 method to detect cell viability daily, calculate the cell number, and draw a growth curve.

[0059] 7.4 Experimental Results like Figure 7As shown, under non-irradiation conditions, no significant promoting effect on the growth of tumor cells was observed after mannose treatment, and cell growth was inhibited after irradiation. Mannose pretreatment did not significantly promote or inhibit the growth of cells after irradiation.

[0060] Example 8 D-mannose does not reduce the sensitivity of colorectal tumors to radiotherapy 8.1 Experimental animals: C57BL / 6J mice, male, 4-6 weeks old, weighing 18-20 g.

[0061] 8.2 Experimental groups: The mice were divided into normal control group (Vehicle), simple drug administration group (Mannose), irradiation control group (IR) and mannose administration group (IR+Mannose).

[0062] 8.3 Administration: Mannose is dissolved in physiological saline and is ready for use.

[0063] 8.4 Experimental steps: (1) Dextran sulfate sodium (DSS) and azoxymethane (AOM)-induced colon cancer model: After intraperitoneal injection of 10 mg / kg AOM, mice were fed with drinking water containing 2% DSS for 5 consecutive days, followed by a 2-day rest period in which they were fed with drinking water without DSS. This cycle was repeated four times in total. After the last cycle, the model was considered successful when tumor formation was confirmed by small animal endoscopy. (2) The mice with successful modeling were randomly divided into groups, with 7 mice in each group; (3) Mice were treated with medication and / or irradiation according to the group. The irradiation conditions were: local X-ray irradiation of the lower abdomen of mice, 2 Gy each time, for 5 consecutive days. The medication conditions were intraperitoneal injection of mannose 100 mg / kg, 2 hours before each irradiation. (4) Endoscopic observation of the tumor after radiotherapy; (5) The mice were killed and the number and diameter of tumors were counted under a stereomicroscope.

[0064] 8.5 Experimental results: Figure 8As shown in the figure, scattered multiple intestinal tumors can be seen in the colon of mice that did not receive radiotherapy. The tumor volume was large, accounting for about 1 / 3-1 / 2 of the intestinal wall. The growth of tumors did not change significantly after simple administration of mannose. The tumor volume was significantly reduced after radiotherapy. No significant effect on the radiotherapy effect was observed after administration. Mice were killed after radiotherapy, and the number and size of tumors were counted. The results were consistent with those of endoscopy. The number of tumors in the CTR group was about (9.57±2.76), of which the proportions of tumors with diameters less than 2mm, between 2mm-5mm, and greater than 5mm were 29.85%, 62.69%, and 7.46%, respectively. There was no significant difference in the number and size of tumors in the Mannose group compared with the IR group. After radiotherapy, the number of colorectal tumors decreased to (5±4.31), and all tumors with a diameter of more than 5mm disappeared, indicating that radiotherapy has a killing effect on tumors. There was no significant difference in the number and size of tumors in the (IR+Mannose) group compared with the IR group.

[0065] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of D-mannose in the preparation of medicines; the medicines are used for at least one of the following aspects: (1) Prevent, alleviate or treat intestinal damage caused by ionizing radiation, intestinal villus damage, intestinal barrier destruction or decreased intestinal epithelial regeneration capacity; (2) Reduce the death of intestinal organoids caused by ionizing radiation; (3) Radioprotection of intestinal organoids.

2. The use according to claim 1, characterized in that: The intestinal damage disease caused by ionizing radiation is radiation enteritis.

3. The use according to claim 2, characterized in that: The radiation enteritis is caused by radiotherapy of pelvic malignant tumors and / or abdominal malignant tumors and / or retroperitoneal malignant tumors.

4. The use according to claim 1, characterized in that: The medicine comprises D-mannose and pharmaceutically acceptable auxiliary materials.

5. The use according to claim 1, characterized in that: The dosage form of the drug is a solid preparation or a liquid preparation.

6. The use according to claim 5, characterized in that: The solid preparation is powder, granule, capsule or tablet, and the liquid preparation is oral solution or injection.

7. The use according to any one of claims 1 to 6, characterized in that: The drug does not reduce the radiosensitivity of intestinal tumor cells.

8. The use according to claim 1, characterized in that: The drug achieves its application purpose through at least one of the following approaches: (1) Promote the regeneration of small intestinal crypts after irradiation; (2) Inhibit irradiation-induced apoptosis of small intestinal crypt cells; (3) Promote the recovery of intestinal villi after irradiation.

9. The use according to claim 1, characterized in that: The drug achieves its application purpose by protecting the intestinal epithelial barrier.

10. The use according to claim 1, characterized in that: The medicine achieves the application purpose by protecting small intestinal stem and progenitor cells.

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