Application of Importazole in obesity

Abstract

The invention provides an application of Importazole in obesity, and belongs to the technical field of biological medicines. The invention provides an application of Importazole (IPZ) in preparation of drugs for treating obesity and / or obesity-related metabolic syndromes, when IPZ is used for treating obese mice, the weight of the mice is reduced, and the values of fasting blood-glucose, serum triglyceride, cholesterol and liver triglyceride are obviously reduced, so that the method has a good treatment effect on obesity and the obesity-related metabolic syndromes. In addition, in the administration period, mice do not have obvious adverse reactions or side effects, and it is indicated that the method has high safety.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and specifically relates to the use of Importazole in obesity. Background Art

[0002] Obesity, as a global metabolic disease, its pathological mechanisms involve multi-dimensional factors such as imbalance between energy intake and consumption, disorder of neuroendocrine regulation, and dysbiosis of gut microbiota. Complications such as type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease caused by it lead to a sharp increase in the medical burden. Currently, the widely accepted treatment options for obesity in clinical practice include lifestyle interventions, such as dieting and exercise to reduce calorie intake; drug treatment, which controls weight by suppressing appetite or reducing calorie absorption; for extremely obese patients, surgical treatment is also an effective option.

[0003] Importazole (IPZ) is a small molecule inhibitor that specifically targets the nuclear transport receptor importin-β. By interfering with its interaction with cargo molecules, it regulates the nucleocytoplasmic transport process, thereby affecting key biological functions such as cell signal transduction, gene expression, and cell cycle. In addition, IPZ can inhibit cell proliferation and induce apoptosis of multiple myeloma cells by inhibiting the NF-κB signaling pathway in vitro. Existing studies related to Importazole mainly focus on nucleocytoplasmic transport mechanisms, tumor treatment applications, etc., but lack research on the role of IPZ in obesity. Summary of the Invention

[0004] The present invention provides the use of Importazole (IPZ) in obesity, and IPZ has a good therapeutic effect on obesity and its related metabolic syndromes.

[0005] The present invention provides the application of Importazole in the preparation of a drug for treating obesity and / or obesity-related metabolic syndromes.

[0006] In a preferred embodiment of the present invention, the drug has at least one of the following therapeutic effects: reducing body weight, reducing fasting blood glucose content, reducing serum triglyceride content, reducing cholesterol content, and reducing liver triglyceride content.

[0007] The present invention also provides a drug for treating obesity, the active ingredient of which includes Importazole, and also includes pharmaceutically acceptable excipients.

[0008] The present invention also provides the application of Importazole in the preparation of a weight loss product.

[0009] The present invention also provides a weight loss product, which includes Importazole and food-acceptable excipients.

[0010] The present invention also provides the use of Importazole in the preparation of health products for assisting in reducing blood lipid.

[0011] The present invention also provides a health product for assisting in reducing blood lipid, comprising Importazole and food-acceptable excipients.

[0012] The present invention also provides the use of Importazole in the preparation of drugs for reducing blood glucose or health products for assisting in reducing blood glucose.

[0013] The present invention also provides a drug for reducing blood glucose, the active ingredient of which comprises Importazole and also comprises pharmaceutically acceptable excipients.

[0014] The present invention also provides a drug for treating obesity-related metabolic syndrome, the active ingredient of which comprises Importazole and also comprises pharmaceutically acceptable excipients.

[0015] Beneficial effects: The present invention provides the use of IPZ in the preparation of drugs for treating obesity and / or obesity-related metabolic syndrome. IPZ is a novel small molecule compound. The IPZ of the present invention can provide new ideas for the treatment of obesity. The results of the examples show that when using IPZ to treat obese mice, their body weight decreases, and the values of fasting blood glucose, serum triglyceride, cholesterol, and liver triglyceride all decrease significantly, indicating that this method has a good therapeutic effect on obesity and its related metabolic syndrome. And during the administration period, the mice did not show obvious adverse reactions or side effects, indicating that this method has high safety. Description of the Drawings

[0016] Figure 1 It is the blood glucose measurement result of the experimental group and the control group mice before drug administration;

[0017] Figure 2 It is the change of the body weight of the mice during the treatment;

[0018] Figure 3 It is the body weight change rate of the mice during the treatment;

[0019] Figure 4 It is the food intake of the mice during the treatment;

[0020] Figure 5 It is the blood glucose result of the experimental group and the control group mice after drug administration;

[0021] Figure 6 It is the weight of the unilateral iWAT of the experimental group and the control group mice;

[0022] Figure 7 It is the weight of the unilateral BAT of the experimental group and the control group mice;

[0023] Figure 8 Results graph of serum triglyceride in experimental and control group mice;

[0024] Figure 9 Results graph of total cholesterol in serum of experimental and control group mice;

[0025] Figure 10 Results graph of high - density lipoprotein in serum of experimental and control group mice;

[0026] Figure 11 Results graph of low - density lipoprotein in serum of experimental and control group mice;

[0027] Figure 12 Results graph of liver triglyceride in experimental and control group mice. Detailed implementation mode

[0028] The present invention provides the application of IPZ in the preparation of drugs for treating obesity and / or obesity - related metabolic syndromes.

[0029] The IPZ described in the present invention was purchased from Med Chem Express (CAS: 662163 - 81 - 7), and the product purity is 99.71%.

[0030] In the examples of the present invention, by constructing an obese mouse model and using IPZ to treat obese mice, their body weight decreased, and the values of fasting blood glucose, serum triglyceride, cholesterol, and liver triglyceride all decreased significantly, indicating that this method has a good therapeutic effect on obesity and its related metabolic syndromes. And during the administration period, no obvious adverse reactions or side effects occurred in the mice, indicating that this method has high safety.

[0031] The present invention also provides a drug for treating obesity, the active ingredient includes IPZ, and also includes pharmaceutically acceptable excipients.

[0032] The present invention has no special limitation on the dosage form of the drug, and conventional pharmaceutical dosage forms in the art can be used, such as decoctions, mixtures (oral liquids), syrups, extract pastes, medicinal wines, fluid extracts, powders, granules (pills), pills, tablets or capsules for gastrointestinal administration, and enemas or suppositories for rectal administration. The present invention can select appropriate excipients for preparation according to different dosage forms.

[0033] The present invention also provides the application of IPZ in the preparation of weight - loss products.

[0034] In the examples of the present invention, by using IPZ to treat obese mice, the body weight of obese mice can be reduced, which has the effect of weight loss.

[0035] The present invention also provides a weight - loss product, including IPZ and food - acceptable excipients.

[0036] The weight loss products described in the present invention can be drugs or health foods. The present invention does not particularly limit the dosage form of the weight loss products either.

[0037] The present invention also provides the use of IPZ in the preparation of health foods for assisting in reducing blood lipid.

[0038] After treating obese mice with the IPZ described in the present invention, the blood lipid content of the obese mice decreased, such as the values of serum triglyceride, cholesterol, and liver triglyceride all decreased significantly.

[0039] The present invention also provides a health food for assisting in reducing blood lipid, which includes IPZ and food-acceptable excipients.

[0040] The present invention does not particularly limit the dosage form of the health food either.

[0041] The present invention also provides the use of IPZ in the preparation of drugs for reducing blood glucose or health foods for assisting in reducing blood glucose.

[0042] After treating obese mice with the IPZ described in the present invention, the blood glucose content of the obese mice decreased, proving that the IPZ has the effect of reducing blood glucose and can be used in the preparation of drugs for reducing blood glucose or health foods for assisting in reducing blood glucose.

[0043] The present invention also provides a drug for reducing blood glucose, the active ingredient of which includes IPZ, and also includes pharmaceutically acceptable excipients. The present invention does not particularly limit the dosage form of the drug either.

[0044] The present invention also provides a drug for treating obesity-related metabolic syndrome, the active ingredient of which includes IPZ, and also includes pharmaceutically acceptable excipients. The present invention does not particularly limit the dosage form of the drug either.

[0045] To further illustrate the present invention, the uses of Importazole provided by the present invention in obesity are described in detail below in conjunction with examples, but they should not be construed as limiting the protection scope of the present invention.

[0046] Example 1

[0047] I. Establishment of an obesity model

[0048] Eight-week-old male C57 mice were selected and housed in a barrier system with a temperature of 22 ± 0.5°C and a 12-hour light / dark cycle. High-fat diet (XTHF60, Synergy Biotechnology) was provided daily or every two days, and the food intake and weight gain of the mice were observed. The body weight of the mice was measured at a fixed time every week. According to the obesity definition method for C57 mice: if the body weight exceeds 20% of the average value of mice of the same strain and age, it can be determined as obese; a body weight > 35 g in mice was used as the successful standard for establishing an obesity model.

[0049] II. Treatment process of IPZ

[0050] The successfully modeled obese mice were randomly divided into an experimental group (n = 6) and a control group (n = 6). The mice in the experimental group were given the therapeutic drug IPZ by intraperitoneal injection at a dosing regimen of 0.5 mg / kg / d. IPZ was dissolved in normal saline, and the final treatment concentration was 0.5 mg / ml; the mice in the control group were given the blank solvent (normal saline), and a high-fat diet was maintained throughout the experiment.

[0051] The fasting blood glucose of the mice was measured one day before the administration of the therapeutic drug. The specific implementation process was as follows: The mice were fasted overnight for 12 hours before the measurement of fasting blood glucose. Blood from the tip of the mouse's tail was taken using a blood glucose meter and test strips to measure and record the blood glucose results ( Figure 1 ), and there was no significant difference in the fasting blood glucose between the experimental group and the control group before drug administration. After starting the administration of the therapeutic drug, the body weight of the mice was recorded at a fixed time every day ( Figure 2 ). There was no significant difference in the body weight of the two groups of mice before drug administration, and a difference in the body weight of the two groups of mice appeared after the treatment cycle ended; during the treatment period, the rate of body weight decrease in the experimental group of mice was significantly higher than that in the normal saline control group of mice ( Figure 3 ). The experimental results showed that IPZ could inhibit the body weight gain of high-fat diet-fed mice.

[0052] The dosing period was 7 days. During the dosing period, the high-fat diet intake of the experimental group and the control group of mice was recorded at a fixed time every day. The results were as Figure 4 shown. There was no significant difference in the food intake of the two groups of mice during the dosing period. After the dosing ended, the blood glucose of the mice was measured again. The changes in blood glucose before and after dosing in the experimental group and the control group were as Figure 5 shown. The degree of blood glucose decrease in the experimental group of mice was more significant than that in the blank control group of mice. After the blood glucose measurement of the mice, the weights of the iWAT and BAT of the mice were measured respectively ( Figure 6 , Figure 7 ). The weight of the unilateral iWAT of the mice in the IPZ treatment group was significantly lower than that of the control group of mice, and there was no significant difference in the weight of the BAT of the two groups of mice; the values of serum triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, and liver triglyceride were monitored, and the results were as Figures 8 - 12As shown; the reduction degrees of the values of triglyceride, total cholesterol, low-density lipoprotein in the serum of the experimental group mice and triglyceride in the liver are more significant than those of the control group mice, and the content of high-density lipoprotein in the mice treated with IPZ is significantly higher than that of the control group mice, indicating that the alleviation of obesity symptoms by IPZ has achieved results.

[0053] Although the above embodiments have made a detailed description of the present invention, they are only a part of the embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on this embodiment without creative efforts, and these embodiments all belong to the protection scope of the present invention.

Claims

1. Use of Importazole in the preparation of a medicament for treating obesity and / or obesity-related metabolic syndrome.

2. The application according to claim 1, wherein The medicament has at least one of the following therapeutic effects: reducing body weight, reducing fasting blood glucose level, reducing serum triglyceride level, reducing cholesterol level, and reducing liver triglyceride level.

3. A drug for treating obesity, characterized in that, The active ingredient includes Importazole and also includes pharmaceutically acceptable excipients.

4. Use of Importazole in the preparation of a weight loss product.

5. A weight loss product, characterized in that, It includes Importazole and food acceptable excipients.

6. Use of Importazole in the preparation of a health product for assisting in reducing blood lipid.

7. A health product for assisting in reducing blood lipid, characterized in that, It includes Importazole and food acceptable excipients.

8. Use of Importazole in the preparation of a medicament for reducing blood glucose or a health product for assisting in reducing blood glucose.

9. A hypoglycemic drug, characterized in that, The active ingredient includes Importazole and also includes pharmaceutically acceptable excipients.

10. A drug for treating obesity and its related metabolic syndromes, characterized in that, The active ingredient includes Importazole and also includes pharmaceutically acceptable excipients.

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