Use of progesterone and analogs for the preparation of a medicament or preparation for the prevention and treatment of intestinal diseases

Abstract

The application belongs to the technical field of biological medicine, and discloses application of progesterone and analogues in preparation of medicines or preparations for preventing or treating intestinal diseases, including application in preparation of medicines or preparations for enhancing intestinal dryness, preventing and treating intestinal injury. Compared with the prior art, the application firstly discovers and proves that progesterone can obviously enhance intestinal dryness, promote repair of intestinal injury, and is used for treating radiation enteritis, inflammatory bowel disease and the like, and has no side effect.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of progesterone and its analogues in the preparation of drugs or formulations for the prevention and treatment of intestinal damage. Background Technology

[0002] Intestinal diseases can be classified in various ways, including inflammatory bowel disease, allergic bowel disease, and functional bowel disease, and can affect people of all ages. Current treatments for intestinal diseases are primarily symptomatic, based on the possible triggers. Methods include allergen avoidance, enteral nutrition, and the use of corticosteroids, immunosuppressants, and biologics to suppress the inflammatory response. Long-term use of these medications may have toxic side effects on organ function, increase the risk of infection, and potentially induce malignant tumors such as lymphoma, especially in children who are still growing and developing.

[0003] Intestinal stem cells are self-renewing cells that can differentiate into various cell types, playing a crucial role in maintaining the structure and function of the intestinal tissue. Research into how to maintain and enhance intestinal stemness provides new insights for the treatment of intestinal diseases.

[0004] Radiation enteritis refers to intestinal radiation damage caused by radiotherapy in patients with pelvic malignancies, such as cervical cancer, endometrial cancer, ovarian cancer, prostate cancer, rectal cancer, and bladder cancer. 81% of patients undergoing pelvic radiotherapy experience gastrointestinal symptoms, including but not limited to rectal bleeding, urgency, diarrhea, tenesmus, and anal pain, which can even progress to perforation, fistula formation, and fecal incontinence. Currently, nonsteroidal anti-inflammatory drugs (NSAIDs) (sulfasalazine, balsalazine, mesalazine, olsalazine, etc.) and corticosteroids (prednisolone, betamethasone, and hydrocortisone) are commonly used clinically. However, there is insufficient evidence to suggest that these drugs enhance intestinal dryness. These two types of drugs often cause side effects such as nausea, anorexia, erythema and itching, headache, palpitations, or Cushing's syndrome, which are extremely detrimental to the patient's recovery after radiotherapy.

[0005] Other intestinal injury diseases, including radiation enteritis and colitis, such as inflammatory bowel disease, irritable bowel syndrome, intestinal infection, intestinal ischemia, drug-induced intestinal injury, radiation enteritis, intra-abdominal infection, and intestinal diseases caused by autoimmune diseases, all involve damage to intestinal epithelial cells in their pathological features. In the laboratory, X-ray or gamma-ray irradiation of mice is commonly used to simulate radiation enteritis, and dextran sulfate sodium (DSS) is used to simulate ulcerative colitis to study the mechanisms and treatment of enteritis. If a drug can be developed to enhance intestinal dryness, it can enhance the regenerative function of intestinal epithelial cells, maintain the intestinal barrier formed by intestinal epithelial cells, ensure the absorption of nutrients, and prevent harmful substances, bacteria, and toxins from penetrating the intestinal wall.

[0006] Currently, all medications used to treat intestinal diseases have strong side effects, especially those used to treat radiation enteritis, which are detrimental to the recovery of radiotherapy patients. Summary of the Invention

[0007] The purpose of this invention is to overcome the defects of the prior art by providing the application of progesterone and its analogues in the preparation of drugs or preparations for the prevention and treatment of intestinal damage. This can maintain and enhance intestinal dryness, thereby promoting the proliferation of intestinal epithelial cells, strengthening the intestinal barrier function and enhancing the absorption of nutrients by the intestine. It can also resist intestinal radiation damage, promote intestinal regeneration and repair after radiation, improve the morphological changes of the intestine caused by radiation damage, and improve individual survival rate.

[0008] The objective of this invention can be achieved through the following technical solution: the application of progesterone and its analogues in the preparation of drugs or formulations for the prevention and treatment of intestinal diseases.

[0009] Furthermore, the molecular formula of the progesterone is C0 21 H 30 O2, the structural formula is as follows:

[0010]

[0011] The structures of the progesterone analogues mentioned above include, but are not limited to, those listed below:

[0012]

[0013]

[0014] Furthermore, progesterone analogues include medroxyprogesterone acetate, megestrol acetate, and dydrogesterone, such as medroxyprogesterone acetate from Zhejiang Xianju Pharmaceutical Co., Ltd., megestrol acetate tablets from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd., and dydrogesterone tablets from Aurite Pharmaceutical Co., Ltd.

[0015] Furthermore, the active ingredient of the drug or preparation is progesterone and / or a progesterone analogue.

[0016] Furthermore, the drug or formulation may also include pharmaceutically acceptable excipients and / or carriers.

[0017] Furthermore, the dosage form of the drug or preparation is selected from capsules, tablets, injections, suppositories, or nebulizers.

[0018] The present invention also provides the use of progesterone and its analogues in the preparation of drugs or formulations that enhance intestinal dryness.

[0019] The present invention also provides the use of progesterone and its analogues in the preparation of medicaments or formulations for the prevention or treatment of intestinal damage.

[0020] Furthermore, the drugs or preparations for preventing and treating intestinal damage include drugs or preparations for preventing or treating inflammatory bowel disease, irritable bowel syndrome, intestinal infection, intestinal ischemia, drug-induced intestinal injury, radiation enteritis, intra-abdominal infection, intestinal diseases caused by autoimmune diseases, or intestinal complications after radiotherapy.

[0021] Furthermore, the instructions for the drug or preparation state that the dosage of progesterone and its analogues is 1–250 mg / kg, preferably 50–150 mg / kg; and that the administration route of progesterone and its analogues is oral or injectable.

[0022] Currently, progesterone is mainly used to regulate menstrual cycles, support pregnancy, alleviate menopausal symptoms, and treat endometriosis and polycystic ovary syndrome. It also possesses certain anti-inflammatory properties. However, there are currently no studies reporting any effect of progesterone on enhancing intestinal dryness or on preventing or treating intestinal damage. As a commonly used progestin, progesterone has relatively mild side effects. Side effects that may occur after continuous use for several weeks include dizziness, headache, and nausea, but these usually subside naturally after discontinuation and do not require special treatment. There are currently no studies on the effects of progesterone on enhancing intestinal dryness or treating intestinal damage.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1) This invention is the first to discover and confirm the application of progesterone and its analogues in the preparation of drugs or formulations that enhance intestinal dryness and treat intestinal damage and other intestinal diseases. Progesterone is a low-toxicity, safe drug with no side effects, mainly used to regulate the menstrual cycle and maintain pregnancy, but there are no research reports on the use of progesterone to treat intestinal damage. This invention provides a new approach, offering the application of progesterone in the preparation of drugs for treating intestinal damage and enhancing intestinal dryness. Progesterone can enhance intestinal dryness and protect against radiation damage to the intestines.

[0025] 2) Intestinal stem cells are self-renewing cells that differentiate into various cell types, playing a crucial role in maintaining the structure and function of the intestinal tissue. This invention utilizes progesterone and its analogues to prepare drugs or preparations that enhance intestinal stemness. Maintaining and enhancing intestinal stemness can promote the proliferation of intestinal epithelial cells, strengthen the intestinal barrier function, and enhance the absorption of nutrients, thereby improving digestion and absorption, enhancing immune function, and providing new insights for the treatment of intestinal diseases.

[0026] 3) The progesterone and its analogues of the present invention can accelerate the recovery of intestinal cell proliferation and speed up the repair of radiation damage, which can effectively improve the application prospects of progesterone and expand its application value.

[0027] 4) The progesterone and its analogues of the present invention can resist intestinal radiation damage, promote intestinal regeneration and repair after radiation, improve the morphological changes of the intestine caused by radiation damage, and improve individual survival rate.

[0028] 5) In this invention, progesterone was administered to mice in three different physiological and pathological states: normal mice, mice with radiation-induced intestinal injury, and mice with ulcerative colitis. Immunohistochemical staining was used, with OLFM4 antibody as an indicator of intestinal dryness, and the effect of progesterone on Lgr5 was verified. + The role of stem cells has demonstrated that progesterone can enhance intestinal dryness and treat intestinal radiation damage. Attached Figure Description

[0029] Figure 1 Gross diagram of the intestine of a normal mouse after administration of progesterone P4; progesterone causes intestinal distension.

[0030] Figure 2 This is a gross view of the cross-section of the mouse intestine after administration of progesterone P4. Progesterone administration increases the intestinal area.

[0031] Figure 3 The staining pattern of intestinal dryness after progesterone P4 administration shows that progesterone enhances intestinal dryness in normal mice.

[0032] Figure 4 OLFM4 in intestinal crypts after administration of progesterone P4 + A statistical graph of cell counts;

[0033] Figure 5 Lgr5 after administration of progesterone P4 + Fluorescence expression pattern of stem cells;

[0034] Figure 6 This is a staining pattern of intestinal dryness after administration of the progesterone inhibitor RU486, which inhibits intestinal dryness.

[0035] Figure 7 Staining images of the recovery of intestinal stemness damaged by irradiation 2-4 days after progesterone P4 pre-administration, showing that progesterone protects against irradiation-damaged intestinal stemness.

[0036] Figure 8 Pre-administration of progesterone P4 2-4 days before subsequent irradiation damage, OLFM4 in the intestine + A statistical chart of the number of hidden nests;

[0037] Figure 9 The staining pattern shows the proliferation of intestinal cells damaged by irradiation 2-4 days after progesterone P4 pre-administration. Progesterone can accelerate the proliferation of irradiated intestinal cells.

[0038] Figure 10 Schematic diagram of DSS and progesterone P4 administration model;

[0039] Figure 11 Statistical chart of body weight percentage in each group during the DSS modeling and progesterone P4 administration experiments;

[0040] Figure 12 General diagram of colon length in each group during DSS modeling and progesterone P4 administration experiments;

[0041] Figure 13 Statistical graph of colon length in each group during DSS modeling and progesterone P4 administration experiments;

[0042] Figure 14 Images of colonic hematoxylin and eosin staining in each group during DSS modeling and P4 drug administration experiments;

[0043] Figure 15 Tissue damage scoring table for each group in the DSS modeling and progesterone P4 administration experiments. Detailed Implementation

[0044] The embodiments of the present invention are described in detail below. These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and specific operation processes. However, the scope of protection of the present invention is not limited to the following embodiments.

[0045] Progesterone is a steroid, also known as luteinizing hormone. It is a female hormone involved in the menstrual cycle in humans and other animals. Progesterone is also a fertility stimulant, and arguably the most important known fertility stimulant, supporting pregnancy and embryonic development. It is commonly used to regulate menstrual cycles, support pregnancy, alleviate menopausal symptoms, and treat conditions such as endometriosis and polycystic ovary syndrome.

[0046] This invention is the first to discover and confirm the use of progesterone in the preparation of drugs or formulations that enhance intestinal dryness and prevent or treat intestinal damage and other intestinal diseases.

[0047] In one embodiment of the present invention, the present invention provides the use of progesterone and its analogues in the preparation of medicaments or formulations that enhance intestinal dryness, including enhancing intestinal dryness;

[0048] This invention provides progesterone and its analogues that promote the proliferation of intestinal epithelial cells, strengthen the intestinal barrier function, and enhance the absorption of nutrients in the intestine, thereby improving digestion and absorption and enhancing immune function.

[0049] In one embodiment of the present invention, the use of progesterone and its analogues in the preparation of drugs or preparations for the prevention or treatment of intestinal damage includes the prevention or treatment of inflammatory bowel disease, irritable bowel syndrome, intestinal infection, intestinal ischemia, drug-induced intestinal injury, radiation enteritis, intra-abdominal infection, intestinal diseases caused by autoimmune diseases, or intestinal complications after radiotherapy.

[0050] This invention provides progesterone and its analogues that can accelerate the recovery of intestinal cell proliferation and speed up the repair of radiation damage and colitis.

[0051] As used in this invention, "therapeutic effective amount" or "effective dose" refers to a dose of progesterone and the like that is non-toxic but sufficient to achieve the desired biological effect, therapeutic and / or preventative outcome. This outcome may be a reduction and / or alleviation of signs, symptoms or precipitating factors of disease, or any other desired alteration of the biological system. For example, an "effective dose" for therapeutic use is the amount required to produce a significant reduction or alleviation of clinical disease, such as the progesterone and the like disclosed herein, either individually or in amounts containing the progesterone and the like. A suitable effective dose in any individual case can be determined by those skilled in the art using conventional testing.

[0052] As used in this invention, "pharmaceutically acceptable" means that a substance is not biologically or otherwise undesirable, i.e., the substance can be administered to an individual without causing undesirable biological effects or interacting with any component of the composition containing the substance in a harmful manner.

[0053] The term "treatment" and its grammatical synonyms as used herein include achieving therapeutic and / or preventative effects. A therapeutic effect means the eradication or relief of the underlying condition to which treatment is being performed. A therapeutic effect is also achieved through the eradication or relief of one or more physiological symptoms associated with the underlying condition, resulting in observed improvement in the patient, even though the patient may still be suffering from the underlying condition. For preventative effects, the methods of the invention can be implemented in patients at risk of developing intestinal diseases, or in patients who, although the condition may not yet be diagnosed, report one or more physiological symptoms of these conditions, or the compositions of the invention can be administered to these patients.

[0054] As used in this invention, the term "pharmaceutically acceptable carrier" refers to a carrier for therapeutic administration, including various excipients and diluents. This term refers to pharmaceutical carriers that are not essential active ingredients themselves and do not cause excessive toxicity after administration. Suitable carriers are those well known to those skilled in the art. Pharmaceutically acceptable carriers in pharmaceuticals may include liquids such as water, saline, glycerol, and Tween. Additionally, these carriers may contain auxiliary substances such as disintegrants, wetting agents, emulsifiers, pH buffers, etc.

[0055] The effective dosage for a particular application will depend on one or more conditions to be treated, the patient's condition, the formulation and route of administration, and other factors known to those skilled in the art. The determination of the effective dosage of progesterone and its analogues can be accomplished by those skilled in the art according to the disclosure of the present invention, and will be done using conventional optimization techniques.

[0056] The medicaments for the prevention and treatment of intestinal diseases provided by this invention can be prepared into various dosage forms according to different routes of administration, including capsules, tablets, injections, suppositories, or nebulizers. These dosage forms are administered in one of the following ways: by injection, oral ingestion, or via an external storage device.

[0057] Before administration, progesterone and its analogues may be mixed with physiological saline or any other suitable solution known to those skilled in the art. Progesterone and its analogues may be administered in solid (lyophilized) or liquid formulations as required.

[0058] The features mentioned above in this invention, or the features mentioned in the embodiments, can be combined arbitrarily. All features disclosed in this specification can be used in any compositional form, and each feature disclosed in the specification can be replaced by any alternative feature that provides the same, equivalent, or similar purpose. Therefore, unless otherwise specified, the disclosed features are merely general examples of specific or similar features.

[0059] In one embodiment of the present invention, progesterone is used to prepare a drug or preparation for enhancing intestinal dryness and treating intestinal damage and other intestinal diseases, the structural formula of which is as follows:

[0060]

[0061] The raw materials and equipment used in this invention are all commercially available products or conventional technologies in the field, as shown in the following embodiments:

[0062] Materials: Wild-type mice: 8-week-old female C57BL / 6 mice obtained from Vital Rivers.

[0063] Progesterone P4: Purchased from MCE, product number HY-N0437.

[0064] Mifepristone RU486: Purchased from MCE, catalog number HY-13683.

[0065] Sodium dextran sulfate (DSS): Purchased from Thermo Scientific, catalog number J14489-18, lot number 221149.

[0066] DMSO: Purchased from McLean, part number D806645.

[0067] Corn oil: purchased from Maclean's, product number C805618.

[0068] OLFM4: Purchased from CST, part number 39141S.

[0069] Ki67: Purchased from Abcam, part number ab16667.

[0070] The irradiation conditions were as follows: Radsource X-ray irradiator, model RS2000pro-225. All irradiated animals received a single dose of 10 Gy at a dose rate of 1.07 Gy / min, all of which were whole-body irradiations.

[0071] Solvent control group (VC): The solvent control for P4 gavage administration was corn oil;

[0072] The control solvent for intraperitoneal injection of P4 was 10% DMSO + 90% corn oil;

[0073] The solvent control for RU486 is 10% DMSO + 90% corn oil.

[0074] The dosage of P4 is 100-250 mg / kg;

[0075] The dosage of RU486 is 25 mg / kg.

[0076] Sodium dextran sulfate group (DSS): 2.5g of sodium dextran sulfate was dissolved in 100mL of water. Mice were allowed free access to the water, and the solution was changed every 2 days.

[0077] Example 1: The effect of progesterone of the present invention on the normal intestine

[0078] Mice were randomly divided into two groups: a solvent control group (VC) and a progesterone-treated group. The progesterone P4 (MCE, HY-N0437) dosage was 250 mg / kg. Intraperitoneal injections were administered daily for 17 days. Small intestinal tissue was then collected and observed. The progesterone P4-treated group showed significant intestinal dilation and enlargement. Figure 1 and 2 As shown. By Figure 1 Observations show that after administration of progesterone P4, both the cross-sectional area of ​​the intestine and the overall length of the small intestine tend to increase. Figure 2 The image on the left shows a cross-sectional view of the intestine segment after it has been cut open and then rolled up and fixed. Figure 2 The image on the right shows a cross-section of a small segment of the intestine. From multiple angles, it was found that the surface area and length of the intestine tended to increase after progesterone administration.

[0079] This demonstrates that progesterone administration promotes the proliferation of intestinal epithelial cells, strengthens the intestinal barrier function, and enhances the absorption of nutrients in the intestine.

[0080] Example 2: The effect of progesterone of the present invention on enhancing the dryness of normal intestines

[0081] Mice were randomly divided into two groups: a solvent control group (VC) and a progesterone administration group (100 mg / kg P4). The progesterone P4 (MCE, HY-N0437) dosage was 100 mg / kg. Intraperitoneal injections were administered daily for 17 days. Small intestinal tissue was then collected and subjected to immunohistochemical staining. Intestinal stemness was labeled with an OLFM4 (olfactory protein 4, a typical marker of intestinal stemness) antibody. Figure 3 The intestinal dryness graphs were obtained from the VC group and the 100 mg / kg P4 group after 17 days of administration. The results showed that the color of OLFM4 in the 100 mg / kg P4 group was significantly darker than that in the VC group, indicating that progesterone P4 can enhance intestinal dryness.

[0082] Simultaneously, OLFM4 in the crypts of the VC group and P4 group (100 mg / kg P4 and 250 mg / kg P4) was analyzed. + Cell counts were performed, with 4 mice in each group. The results are as follows: Figure 4 As shown, OLFM4 was found in the crypts after P4 administration. + The cell count was significantly higher than that in the control group. This indicates that P4 can enhance intestinal stemness.

[0083] Lgr5-EGFP mice are a type of mouse developed from Lgr5... + Transgenic mice with stem cells labeled with EGFP (green fluorescent protein) were divided into groups and administered progesterone P4 and vitamin C by gavage at a dose of 100 mg / kg for 14 days. The effect of P4 on Lgr5 was observed. + The role of stem cells. Results are as follows: Figure 5 As shown, the fluorescence range and intensity of Lgr5 increased in the P4-treated group, indicating that progesterone P4 can enhance intestinal dryness.

[0084] Example 3: The inhibitory effect of progesterone inhibitor RU486 on the dryness of normal intestine.

[0085] During pregnancy and lactation, progesterone levels in mice rise sharply and remain high throughout this period. Therefore, female mice that had just given birth were selected as experimental mice and divided into a solvent control group and an RU486 administration group. The dosage of RU486 (MCE, HY-13683) was 25 mg / kg. Small intestinal tissue was collected after 7 days of continuous intraperitoneal injection and subjected to immunohistochemical staining, using OLFM4 as a marker for intestinal stemness. Figure 6 The images show intestinal dryness after 7 days of administration of VC and 25 mg / kg RU486. The results indicate that the color of OLFM4 in the RU486 group was significantly lighter than that in the VC group, suggesting that the progesterone inhibitor RU486 can reduce intestinal dryness. This conversely demonstrates that progesterone can enhance intestinal dryness.

[0086] Example 4: Progesterone has a pre-protective and repairing effect on the small intestine after irradiation.

[0087] Mice were randomly divided into two groups: a solvent control group (VC) and a progesterone group (100 mg / kg P4). After continuous gavage administration for 2-4 days, mice were subjected to X-ray irradiation with a total dose of 10 Gy. Small intestinal tissue was harvested 3.5 days after irradiation and subjected to immunohistochemical staining. OLFM4 was used as a marker of intestinal stemness, such as... Figure 7-8 Four days after progesterone P4 administration, mice were subjected to radiation damage. The results showed that the expression intensity and quantity of OLFM4 in the intestines of mice treated with progesterone P4 were significantly higher than those in the vitamin C group. Furthermore, the expression of OLFM4 in the small intestines of each group was also significantly higher. + The number of crypts was counted. In ImageJ software, the units on the image's scale were converted to indicate the number of small intestine cells per centimeter, and the OLFM4 count within that range was calculated. + crypt count, found OLFM4 in group P4 + The number of crypts was significantly higher in the group than in the vitamin C group, indicating that progesterone can protect intestinal dryness and promote the repair of irradiated intestinal damage.

[0088] Similarly, using Ki67 as a marker of intestinal cell proliferation, and after pre-administration of progesterone P4 for 2 days, mice were subjected to radiation damage experiments using the same method described above. The results were as follows: Figure 9 The study found that the expression level of Ki67 in the intestine of progesterone P4 was significantly higher than that in the VC group, indicating that progesterone can accelerate the proliferation of intestinal cells and speed up the repair of radiation damage.

[0089] Example 5: Progesterone has a therapeutic effect on colitis.

[0090] Mice were divided into two groups: the 2.5% dextran sulfate sodium group (DSS) and the DSS+P4 group, which was simultaneously administered progesterone P4-100 mg / kg via gavage. Specific administration methods are detailed below. Figure 10 DSS modeling resulted in decreased body weight, shortened colon length, inflammatory infiltration of the colonic tissue, and loss of colonic crypt structures in mice. Body weight changes were recorded during the modeling period, and the percentage of body weight in each group was calculated. Results are as follows: Figure 11 As shown in the figure. Compared with the DSS group, the DSS+P4 group experienced less weight loss, indirectly indicating that P4 administration can salvage intestinal damage caused by DSS. The colons of the mice were photographed at the time of tissue collection, and the results are shown below. Figure 12 As shown, compared with the DSS group, the DSS+P4 group had a significantly longer colon. The colon length statistics are shown in the figure below. Figure 13 As shown. Further staining of the mouse colon with hematoxylin and eosin was performed, as shown... Figure 14As shown in the figure. Compared with the DSS group, the colonic crypt structure in the DSS+P4 group was more intact. Simultaneously, histological changes were scored. The scoring was based on the observation and quantification of specific pathological features of the intestinal tissue, which may include inflammatory cell infiltration, crypt structure destruction, epithelial cell damage, etc. A higher score indicates more severe tissue damage. The scoring results are shown in the figure. Figure 15 As shown, the DSS+P4 group had lower histological scores. These results all indicate that P4 has a protective and therapeutic effect against colitis induced by DSS.

[0091] In another embodiment of the present invention, progesterone analogs are used to prepare drugs or preparations that enhance intestinal dryness and treat intestinal damage and other intestinal diseases. Progesterone analogs include medroxyprogesterone acetate, megestrol acetate, dydrogesterone, etc.

[0092] Example 6

[0093] In this embodiment, medroxyprogesterone acetate from Zhejiang Xianju Pharmaceutical Co., Ltd. was selected, and the irradiation experiment was conducted using the same method as in Example 4. The results showed that medroxyprogesterone acetate can also accelerate the recovery of intestinal cell proliferation and speed up the repair of irradiation damage.

[0094] In addition, using the same method as in Example 5, sodium dextran sulfate (DSS) was used to simulate ulcerative colitis, with medroxyprogesterone acetate replacing P4. The results showed that medroxyprogesterone acetate also had a protective and therapeutic effect on colitis induced by DSS.

[0095] Example 7

[0096] In this embodiment, megestrol acetate tablets from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd. were selected, and the irradiation experiment was conducted using the same method as in Example 4. The results showed that megestrol acetate tablets can also accelerate the proliferation of intestinal cells and speed up the repair of irradiation damage.

[0097] In addition, using the same method as in Example 5, sodium dextran sulfate (DSS) was used to simulate ulcerative colitis, and megestrol acetate tablets were used to replace P4. The results showed that megestrol acetate tablets also had a protective and therapeutic effect on colitis caused by DSS.

[0098] Example 8

[0099] In this embodiment, dydrogesterone tablets from Aurite Pharmaceutical Co., Ltd. were selected, and the irradiation experiment was conducted using the same method as in Example 4. The results showed that dydrogesterone tablets can also accelerate the recovery of intestinal cell proliferation and speed up the repair of irradiation damage.

[0100] In addition, using the same method as in Example 5, dextran sulfate sodium DSS was used to simulate ulcerative colitis, and dydrogesterone tablets were used to replace P4. The results showed that dydrogesterone tablets also had a protective and therapeutic effect on colitis caused by DSS.

[0101] Example 9

[0102] In this embodiment, Abbott Biologicals BV's dydrogesterone (Duphaston) was selected, and the irradiation experiment was conducted using the same method as in Example 4. The results showed that Duphaston can also accelerate the recovery of intestinal cell proliferation and speed up the repair of irradiation damage.

[0103] Additionally, using the same method as in Example 5, dextran sulfate sodium DSS was used to simulate ulcerative colitis, with Duphaston replacing P4. The results showed that Duphaston also had a protective and therapeutic effect on colitis induced by DSS.

[0104] Progesterone analogues are substances that have been modified with a small number of groups or chemical bonds based on the progesterone structure, such as medroxyprogesterone acetate, megestrol acetate, and chlorpromazine acetate, which can also have the effect of treating intestinal diseases.

[0105] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the invention patent should be included within the protection scope of the present invention patent.

Claims

1. Application of progesterone and its analogues in the preparation of drugs or formulations for the prevention and treatment of intestinal diseases.

2. The use of progesterone and its analogues according to claim 1 in the preparation of medicaments or formulations for the prevention and treatment of intestinal diseases, characterized in that, The molecular formula of the progesterone mentioned is C 21 H 30 O2, the structural formula is as follows: The structures of the progesterone analogues mentioned above include, but are not limited to, those listed below:

3. The use of progesterone and its analogues according to claim 1 in the preparation of medicaments or formulations for the prevention and treatment of intestinal diseases, characterized in that, The active ingredient of the drug or preparation is progesterone and / or a progesterone analogue.

4. The use of progesterone and its analogues according to claim 1 in the preparation of medicaments or formulations for the prevention and treatment of intestinal diseases, characterized in that, The drug or formulation also includes pharmaceutically acceptable excipients and / or carriers.

5. The use of progesterone and its analogues according to claim 1 in the preparation of medicaments or formulations for the prevention and treatment of intestinal diseases, characterized in that, The dosage form of the drug or preparation is selected from capsules, tablets, injections, suppositories, or nebulizers.

6. Application of progesterone and its analogues in the preparation of drugs or formulations that enhance intestinal dryness.

7. The use of progesterone and its analogues in the preparation of drugs or formulations for the prevention and treatment of intestinal damage.

8. The use of progesterone and its analogues according to claim 7 in the preparation of medicaments or formulations for the prevention and treatment of intestinal damage, characterized in that, The drugs or preparations for the prevention and treatment of intestinal injury include those for the prevention or treatment of inflammatory bowel disease, irritable bowel syndrome, intestinal infection, intestinal ischemia, drug-induced intestinal injury, radiation enteritis, intra-abdominal infection, intestinal diseases caused by autoimmune diseases, or intestinal complications after radiotherapy.

9. The use of progesterone and its analogues according to claim 7 in the preparation of medicaments or formulations for the prevention and treatment of intestinal damage, characterized in that, The instructions for the drug or preparation state that the dosage of progesterone and its analogues is 1-250 mg / kg; and that the administration method for progesterone and its analogues is oral or injectable.

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