Application of 5-bromocytidine in preparation of medicine or health care product for treating hyperuricemia

Abstract

The invention relates to the technical field of medicine, in particular to application of 5-bromocytidine in medicine for treating hyperuricemia, the 5-bromocytidine can effectively reduce the content of uric acid in serum, namely, the 5-bromocytidine has the effect of treating the hyperuricemia.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technologies, and particularly to the use of 5-bromocytidine in the preparation of drugs or health products for treating hyperuricemia. Background Art

[0002] Hyperuricemia is a metabolic disease caused by disorders of purine metabolism and uric acid metabolism in the body, and is considered a risk factor for diseases such as diabetes, cardiovascular diseases, hypertension, and chronic kidney diseases. Under normal purine diet conditions, if the fasting blood uric acid level is higher than 416 μmol / L in men and higher than 360 μmol / L in women on two non-consecutive days, it is called hyperuricemia. Modern high-purine, high-fructose eating habits and irregular work and rest and other factors have made hyperuricemia gradually younger, and the prevalence of hyperuricemia in China has reached 18.4%. Usually, simply being in a state of hyperuricemia has no conscious symptoms, but if in this state for a long time, urate in the blood will crystallize, and then gout symptoms will appear. Metabolic disorders related to hyperuricemia also include acute pain, inflammatory arthritis of a single joint attributed to uric acid crystals, deposition of urate crystals in joints, deposition of urate crystals in renal parenchyma, urolithiasis, nephrolithiasis, and gouty nephropathy. Long-term nephrolithiasis and gouty nephropathy are known to increase the risk of kidney injury and renal failure.

[0003] The treatment of hyperuricemia is mainly to reduce uric acid production or accelerate uric acid excretion. Drugs commonly used clinically are xanthine oxidase inhibitors, urate transporter inhibitors, and uricase, etc. Representative drugs among them are allopurinol, febuxostat, sulfinpyrazone, and fenofibrate, etc. In addition, the symptoms of acute gout can be controlled by anti-inflammatory drugs, such as non-steroidal anti-inflammatory drugs and corticosteroids, etc. However, currently these treatment drugs are associated with several harmful side effects, such as causing allergic vasculitis, liver failure, gastric perforation, etc. Therefore, it is very necessary to develop new drugs for treating gout and hyperuricemia with high efficiency and low side effects.

[0004] Cytidine is one of the pyrimidine nucleosides that make up nucleic acids, composed of cytosine and ribose, and is a necessary compound for life. It is an important pharmaceutical synthesis intermediate in contemporary medicine and has no definite medical use clinically. 5-Bromocytidine is often used as a pharmaceutical synthesis intermediate and has no definite medical use clinically.

[0005] The inventor unexpectedly found during the experiment that cytidine and 5-bromocytidine have the effect of treating hyperuricemia, providing a new use for cytidine and 5-bromocytidine. Summary of the Invention

[0006] In view of the above problems, the present invention provides the use of 5-bromocytidine in the preparation of drugs for treating hyperuricemia, and the 5-bromocytidine shown is represented by the structural formula (I):

[0007]

[0008] Preferably, the 5-bromocytidine is formulated into powder, tablets, granules, capsules, solutions, emulsions, suspensions, or injections by adding pharmaceutically acceptable carriers.

[0009] Preferably, the 5-bromocytidine is formulated into tablets or capsules by adding pharmaceutically acceptable carriers.

[0010] Preferably, the 5-bromocytidine is taken sublingually or by swallowing.

[0011] Preferably, the hyperuricemia is selected from gout or gout complications caused by hyperuricemia.

[0012] Preferably, the gout is selected from acute gout or chronic gout; the gout complications are selected from gouty arthritis, gout attacks, gouty nephropathy, or uric acid kidney stones.

[0013] The second object of the present invention is to provide the use of 5-bromocytidine in the preparation of health products for treating hyperuricemia. The 5-bromocytidine is shown by the structural formula (I):

[0014]

[0015] Preferably, the hyperuricemia is selected from gout or gout complications caused by hyperuricemia.

[0016] Preferably, the gout is selected from acute gout or chronic gout; the gout complications are selected from gouty arthritis, gout attacks, gouty nephropathy, or uric acid kidney stones.

[0017] The beneficial effects of the present invention are as follows: The present invention provides a new use of 5-bromocytidine in the preparation of drugs or health products for treating hyperuricemia. Experimental results show that compared with the model group "Model", in the 5-bromocytidine group "5-Bromocytidine", ** p < 0.01, indicating that 5-bromocytidine can significantly reduce the uric acid in the serum. 5-bromocytidine has the effect of reducing the content of uric acid in the serum, that is, 5-bromocytidine has the function of treating hyperuricemia. Description of the Drawings

[0018] Figure 1 It is a bar chart of the uric acid content in the serum of mice in each administration group provided by the present invention;

[0019] Note: Among them, "Control" is the blank control group without the co - intervention of uric acid and potassium oxonate, "Model" is the model control group with the co - intervention of uric acid and potassium oxonate, and "5 - Bromocytidine" is the 5 - bromocytidine group. When the model control group "Model" is compared with the blank control group "Control", ### p < 0.001; when the 5 - bromocytidine group "5 - Bromocytidine" is compared with the model group "Model", ** p < 0.01. Detailed implementation mode

[0020] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. At the same time, the therapeutic effects of 5 - bromocytidine on all symptoms caused by hyperuricemia are protected, including different dosage forms, dosages, etc. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative labor belong to the scope of protection of the present invention.

[0021] It should be understood that the above brief description and the following detailed description are exemplary and for explanation only, and do not limit the subject matter of the present invention herein. In this application, it must be noted that unless otherwise clearly stated in the text, the singular forms used in this specification and the claims include the plural forms of the referred things. It should also be noted that unless otherwise specified, the used "or", "or" means "and / or". In addition, the used terms "including" and other forms, such as "comprising", "containing", and "having" are not restrictive.

[0022] Example 1. Research on the effect of cytidine in treating hyperuricemia

[0023] 1. Experimental animals

[0024] SPF - grade male Kunming mice at 4 weeks of age, with an average body weight of 18 ± 2 g, were selected and provided by the Medical Experimental Animal Center of Lanzhou University. No drugs were given to the animals before the experiment. The experimental animals were adaptively raised for one week in an environment with a temperature of 24 - 26 °C and a 12h / 12h day - night regular alternation. The animals were given food and free access to water, and then grouped for the experiment.

[0025] 2. Drugs and reagents

[0026] Uric acid was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., batch number: U105582, molecular weight 168.1.

[0027] Potassium oxonate (HPLC ≥ 98.0%) was purchased from Macklin Biotech Co., Ltd., batch number: P137112, molecular weight 195.18.

[0028] 5-Bromocytidine (95%), purchased from Shanghai Bide Pharmaceutical Technology Co., Ltd., batch number: BD103043, molecular weight 322.11.

[0029] 3. Experimental grouping

[0030] Thirty male Kunming mice at 4 weeks of age were randomly divided into a blank control group (Control), a model control group (Model), and a 5-bromocytidine group (5-Bromocytidine), with a total of 3 groups, 10 mice in each group.

[0031] 4. Experimental methods

[0032] Thirty Kunming mice were randomly grouped as described above. The blank control group (Control) was intragastrically administered an equal volume of aqueous solution, and the model group (Model) and the 5-bromocytidine group (5-Bromocytidine) were intragastrically administered 0.5 mL of an aqueous solution containing 2% uric acid and 4% potassium oxonate. One hour after the intragastric administration was completed, the blank control group (Control) and the model group (Model) were intragastrically administered an equal volume of normal saline, and the 5-bromocytidine group (5-Bromocytidine) was intragastrically administered 5-bromocytidine at a dose of 200 mg / kg. The above operations were continuously treated for 14 days. On the 15th day, after fasting but not restricting water for 12 hours in advance, blood samples were collected by taking blood from the inner canthus of the eye. The samples were allowed to stand at room temperature for 30 minutes, centrifuged at 1520 g for 10 minutes at 4 °C, and the supernatant was aspirated to obtain serum.

[0033] 5. Experimental results

[0034] As Figure 1 shown, compared with the blank control group "Control", the model control group "Model" ### p < 0.001, indicating that the hyperuricemia model was successfully constructed; compared with the model group "Model", the 5-bromocytidine group "5-Bromocytidine" ** p < 0.01, indicating that 5-bromocytidine can significantly reduce the uric acid in the serum. In summary, 5-bromocytidine has the effect of reducing the content of uric acid in the serum, that is, 5-bromocytidine has the function of treating hyperuricemia.

Claims

1. Use of 5-bromocytidine in the preparation of a drug for treating hyperuricemia, characterized in that, The 5-bromocytidine is shown by the structural formula (I) as follows:

2. The application according to claim 1, characterized in that, The 5-bromocytidine is formulated into powders, tablets, granules, capsules, solutions, emulsions, suspensions, or injections by adding pharmaceutically acceptable carriers.

3. The application according to claim 2, characterized in that, The 5-bromocytidine is formulated into tablets or capsules by adding pharmaceutically acceptable carriers.

4. The application according to claim 3, characterized in that, The 5-bromocytidine is taken by sublingual administration or swallowing.

5. The application according to claim 1, characterized in that The hyperuricemia is selected from gout or gout complications caused by hyperuricemia.

6. The application according to claim 5, characterized in that, The gout is selected from acute gout or chronic gout; the gout complications are selected from gouty arthritis, gout attacks, gouty nephropathy, or uric acid kidney stones.

7. Application of 5-bromocytidine in preparing health products for treating hyperuricemia, characterized in that, The 5-bromocytidine is shown by the structural formula (I) as follows:

8. The application according to claim 7, characterized in that, The hyperuricemia is selected from gout or gout complications caused by hyperuricemia.

9. The application according to claim 8, wherein, The gout is selected from acute gout or chronic gout; the gout complications are selected from gouty arthritis, gout attacks, gouty nephropathy, or uric acid kidney stones.

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