Application of clofarabine in obesity treatment

Abstract

The invention provides application of clofarabine in obesity treatment, and belongs to the technical field of biological medicines. The invention provides the application of clofarabine in obesity treatment, and a new thought can be provided for obesity treatment. An obese mouse model is utilized, clofarabine is used for treating an obese mouse, the weight of the obese mouse is reduced, and the values of fasting blood-glucose, serum triglyceride, cholesterol and liver triglyceride are obviously reduced, so that clofarabine has a good treatment effect on obesity and related metabolic syndromes. Meanwhile, in the administration period, mice do not have obvious adverse reactions or side effects, which indicates that the clofarabine has high safety.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of clofarabine in the treatment of obesity. Background Art

[0002] Obesity, a global public health crisis, has left over 650 million patients at risk of metabolic syndrome (e.g., type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease). Its pathological mechanisms involve multidimensional factors, including imbalances in energy intake and expenditure, neuroendocrine regulation disorders, and intestinal microbiome dysbiosis. Currently, widely accepted clinical treatments for obesity include lifestyle interventions, such as dieting and exercise to reduce calorie intake; medications to control weight by suppressing appetite or reducing calorie absorption; and, for extremely obese patients, surgical treatment is also an effective option.

[0003] Clofarabine is an anti-tumor drug that inhibits enzymes involved in DNA synthesis in various ways. Clofarabine is active against a variety of solid tumors and is particularly effective in treating acute leukemia. As a purine nucleoside analog approved for the treatment of childhood leukemia, its anti-cancer mechanism relies on inhibiting DNA synthesis and inducing tumor cell apoptosis. However, existing patents and literature focus primarily on its application in hematological malignancies, while its metabolic regulation potential remains largely unexplored. Summary of the Invention

[0004] The present invention provides the use of clofarabine in the treatment of obesity. The clofarabine has a good therapeutic effect on obesity and related metabolic syndrome.

[0005] The present invention provides the use of clofarabine in preparing a medicine for treating obesity.

[0006] In a preferred embodiment of the present invention, the treatment of obesity includes at least one of the following: reducing body weight, reducing fasting blood sugar content, reducing serum triglyceride content, reducing cholesterol content and reducing liver triglyceride content.

[0007] The present invention provides a medicine for treating obesity, comprising clofarabine and pharmaceutically acceptable excipients.

[0008] In a preferred embodiment of the present invention, the administration of the drug includes gastrointestinal administration and / or rectal administration.

[0009] In a preferred embodiment of the present invention, the dosage form for gastrointestinal administration includes: decoction, mixture, syrup, decoction, wine, fluid extract, powder, granule, pill, tablet or capsule.

[0010] In a preferred embodiment of the present invention, the dosage form for rectal administration includes: enema or suppository.

[0011] The present invention provides the use of clofarabine in preparing a medicine for treating obesity-related metabolic syndrome.

[0012] The present invention provides a medicine for treating obesity-related metabolic syndrome, comprising clofarabine and pharmaceutically acceptable excipients.

[0013] The present invention provides the use of clofarabine in preparing a health product for weight loss, auxiliary blood sugar reduction and / or auxiliary blood lipid reduction.

[0014] The present invention provides a health product capable of reducing weight, assisting in lowering blood sugar and / or assisting in lowering blood lipids, comprising clofarabine and a food-acceptable auxiliary material.

[0015] Beneficial Effects: The present invention provides the use of clofarabine in the treatment of obesity. Using an obese mouse model, treatment with clofarabine resulted in weight loss, and significant reductions in fasting blood glucose, serum triglycerides, cholesterol, and liver triglyceride levels, demonstrating that clofarabine has a beneficial therapeutic effect on obesity and its associated metabolic syndrome. Furthermore, during administration, the mice experienced no significant adverse reactions or side effects, demonstrating the high safety of clofarabine. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 These are the blood glucose measurement results of mice in the experimental and control groups before administration;

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

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

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

[0020] Figure 5 The blood glucose results of the experimental and control group mice after administration;

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

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

[0023] Figure 8 The results of serum triglyceride in experimental and control group mice are shown in the figure;

[0024] Figure 9 The results of total cholesterol in serum of mice in the experimental and control groups are shown in the figure;

[0025] Figure 10 The results of serum high-density lipoprotein in experimental and control groups of mice are shown in the figure;

[0026] Figure 11 The results of serum low-density lipoprotein in experimental and control groups of mice;

[0027] Figure 12 The results of liver triglyceride in experimental and control groups of mice are shown in Figure 2. DETAILED DESCRIPTION

[0028] The present invention provides the use of clofarabine in preparing a medicine for treating obesity.

[0029] The clofarabine described in the present invention was purchased from MedChemExpress (CAS: 123318-82-1), and the product purity was 99.88%.

[0030] The clofarabine described in the present invention has anti-metabolic properties. In an embodiment of the present invention, an obese mouse model was constructed and clofarabine was administered to the model. The results showed that the obese mice lost weight, and the fasting blood sugar, serum triglyceride, cholesterol and liver triglyceride values were significantly reduced through clofarabine treatment, indicating that clofarabine has a good therapeutic effect on obesity and its related metabolic syndrome.

[0031] The present invention provides a medicine for treating obesity, comprising clofarabine and pharmaceutically acceptable excipients.

[0032] The administration mode of the drug of the present invention includes gastrointestinal administration and / or rectal administration, wherein the dosage form for gastrointestinal administration includes: decoction, mixture, syrup, decoction, wine, fluid extract, powder, granule, pill, tablet or capsule; the dosage form for rectal administration includes: enema or suppository.

[0033] The present invention provides the use of clofarabine in preparing medicines for treating obesity and related metabolic diseases.

[0034] Metabolic syndrome, as described in this article, is a pathological state characterized by abnormal metabolism of proteins, fats, carbohydrates, and other substances in the human body. It is a complex group of metabolic disorders that contribute to risk factors for diabetes and cardiovascular and cerebrovascular diseases. Primary clinical manifestations include obesity, hypertension, dyslipidemia, diabetes or impaired glucose tolerance, insulin resistance, and microalbuminuria. Secondary manifestations include hyperuricemia, hyperphosphatemia, and hypofibrinolysis, as well as polycystic ovary syndrome and hyperhomocysteinemia.

[0035] The examples of the present invention demonstrate that after treatment with clofarabine, the weight of obese mice decreased, and the values of fasting blood glucose, serum triglycerides, cholesterol, and liver triglycerides were significantly reduced, indicating that clofarabine has a good therapeutic effect on obesity and its related metabolic syndrome.

[0036] The present invention provides a medicine for treating obesity and related metabolic syndrome, comprising clofarabine and pharmaceutically acceptable excipients.

[0037] The present invention has no particular limitation on the dosage form of the drug.

[0038] The present invention provides the use of clofarabine in preparing a health product for weight loss, auxiliary blood sugar reduction and / or auxiliary blood lipid reduction.

[0039] The present invention provides a health product capable of reducing weight, assisting in lowering blood sugar and / or assisting in lowering blood lipids, comprising clofarabine and a food-acceptable auxiliary material.

[0040] The present invention does not specifically limit the dosage form of the health care product, and mainly adopts oral dosage forms, including: decoction, mixture, syrup, decoction, wine, fluid extract, powder, granule, pill, tablet or capsule.

[0041] To further illustrate the present invention, the application of clofarabine provided by the present invention in the treatment of obesity is described in detail below with reference to the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0042] Example 1

[0043] 1. Establishment of obesity model

[0044] Eight-week-old male C57 mice were housed in a 12-hour light / dark cycle at 22 ± 0.5°C. A high-fat diet (Synergy Biotech, #XTHF60) was administered daily or every two days, and the mice's food intake and weight gain were observed. Mice were weighed weekly. According to the C57 mouse obesity standard, mice were considered obese if their weight exceeded the average for mice of the same strain and age by more than 20%. A successful obesity model was established when the weight exceeded 35 g.

[0045] 2. Treatment process of clofarabine

[0046] Successfully established obese mice were randomly divided into an experimental group (n=6) and a control group (n=6). The experimental group received clofarabine at a dose of 0.5 mg / kg / day via intraperitoneal injection. Clofarabine was administered in saline solution at a final concentration of 0.5 mg / ml. The control group received a blank solution (saline) and maintained a high-fat diet throughout the experiment.

[0047] The fasting blood glucose of mice was measured one day before the administration of the therapeutic drug. The specific implementation process was as follows: the mice were fasted for 12 hours overnight before the fasting blood glucose measurement, and blood glucose was measured by using a blood glucose meter and blood glucose test strips to collect blood glucose from the tip of the mouse tail and record the results ( Figure 1 ), there was no significant difference in fasting blood glucose between the experimental group and the control group before administration. The weight of the mice was recorded at a fixed time every day after the treatment began. Figure 2 ), there was no significant difference in body weight between the two groups of mice before administration, but there was a difference in body weight between the two groups of mice after the treatment period; the rate of weight loss in the experimental group during treatment was significantly higher than that in the normal saline control group ( Figure 3 The experimental results showed that clofarabine could inhibit the weight gain of mice fed a high-fat diet.

[0048] The administration period was 7 days. The high-fat diet intake of the experimental and control mice was recorded every day during the administration period. The results are as follows: Figure 4 As shown in the figure, the food intake of the two groups of mice was similar during the administration period. After the administration, the blood glucose of the mice was measured again. The changes in blood glucose before and after administration in the experimental group and the control group are shown in the figure. Figure 5 As shown in Figure 2, the blood glucose level of the experimental group mice decreased more significantly than that of the blank control group mice. After the blood glucose measurement of the mice was completed, the weight of iWAT and BAT of the mice were measured ( Figure 6 、 Figure 7 ), the unilateral iWAT weight of mice in the clofarabine treatment group was significantly lower than that in the control group, and there was no significant difference in the unilateral BAT weight between the two groups of mice; the levels of serum triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and liver triglyceride were monitored, and the results were as follows Figures 8-12 As shown, the reduction in serum triglycerides, total cholesterol, low-density lipoprotein and liver triglycerides in the experimental group of mice was more significant than that in the control group, while the content of high-density lipoprotein in mice treated with clofarabine was significantly higher than that in the control group, indicating that clofarabine has been effective in alleviating obesity symptoms.

[0049] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. Use of clofarabine in the preparation of drugs for treating obesity.

2. The application according to claim 1, characterized in that The treatment of obesity includes at least one of the following: reducing body weight, reducing fasting blood sugar content, reducing serum triglyceride content, reducing cholesterol content and reducing liver triglyceride content.

3. A drug for treating obesity, characterized in that: The invention comprises clofarabine and pharmaceutically acceptable excipients.

4. The drug according to claim 3, characterized in that The administration of the drug includes gastrointestinal administration and / or rectal administration.

5. The drug according to claim 4, characterized in that The dosage forms for gastrointestinal administration include: decoction, mixture, syrup, decoction, wine, fluid extract, powder, granule, pill, tablet or capsule.

6. The drug according to claim 4, characterized in that The dosage form for rectal administration includes: enema or suppository.

7. Use of clofarabine in the preparation of drugs for treating obesity-related metabolic syndrome.

8. A drug for treating obesity-related metabolic syndrome, characterized in that: The invention comprises clofarabine and pharmaceutically acceptable excipients.

9. Use of clofarabine in the preparation of health products for weight loss, auxiliary blood sugar reduction and / or auxiliary blood lipid reduction.

10. A health product that can help reduce weight, lower blood sugar and / or lower blood lipids, characterized in that: Comprising clofarabine and food-acceptable excipients.

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