Application of micromolecular N-methyldodecylamine in preparation of medicine for preventing and treating chronic kidney disease and hyperuricemia

Abstract

The invention belongs to the field of biological medicines, and provides application of micromolecular N-methyldodecylamine in preparation of medicines for preventing and treating chronic kidney diseases and reducing uric acid. Experimental results show that the N-methyldodecylamine can be used for remarkably reducing kidney function related index values in a chronic kidney disease model caused by adenine intake, such as serum creatinine (SCr), blood urea nitrogen (BUN), uric acid (UA) and urine protein in urine, and the N-methyldodecylamine can be used for remarkably reducing the kidney function related index values in the chronic kidney disease model caused by adenine intake, such as serum creatinine (SCr), blood urea nitrogen (BUN), uric acid (UA) and urine protein in urine. The small molecule provides a candidate molecule for clinical treatment of chronic kidney disease and hyperuricemia.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to application of a small molecule N-methyldodecylamine in the preparation of drugs for preventing and treating chronic kidney disease and hyperuricemia. Background Art

[0002] Chronic kidney disease (CKD) is a global health problem in both developed and developing countries. It manifests as a gradual and irreversible deterioration of renal function, with the rate of functional decline depending on the severity of the disease and the patient's coexisting conditions. The number of patients affected by CKD worldwide has reached approximately 843.6 million. There are many factors that contribute to the development of CKD, including but not limited to hypertension, diabetes, glomerulonephritis, polycystic kidney disease, and long-term use of certain medications. In addition, certain lifestyle factors (such as smoking, obesity, and a high-salt diet and processed foods) can exacerbate the progression of CKD. The progression of CKD is often asymptomatic until renal failure develops, requiring renal replacement therapy. Without appropriate intervention, the consequences of renal failure (including uremia, anemia, and electrolyte metabolism disorders) can be fatal. In addition, CKD increases the likelihood of cardiovascular events and significantly affects the patient's overall health and quality of life. Despite extensive efforts to find effective treatments for the progression of tubulointerstitial fibrosis, some forms of CKD lack therapeutic solutions. Currently, strategies for managing chronic kidney disease depend on regulating hypertension through renin-angiotensin system (RAS) inhibition and angiotensin II receptor blockers (ARBs) targeting the RAS, as well as immunosuppressants and corticosteroids. Treatment options for chronic kidney disease are aimed at slowing its progression, controlling complications, and improving overall quality of life. Lifestyle changes, such as maintaining a healthy diet low in sodium and potassium, regular exercise, and smoking cessation, are important components of chronic kidney disease management. Controlling blood pressure and blood sugar levels through medication and monitoring is essential, especially for patients with hypertension and diabetes. Although previous research has focused on novel and effective treatments, the availability of successful drugs that prevent or delay the progression of chronic kidney disease remains limited. Therefore, it is crucial to identify new drugs that can effectively manage chronic kidney disease.

[0003] For the above problems, experimental studies have shown that the small molecule N-methyl dodecylamine described in the present invention can significantly reduce renal function-related indicators such as serum creatinine, blood urea nitrogen, and blood uric acid in a chronic kidney disease model caused by adenine, and reduce the concentration of urine protein in urine, thereby effectively improving the renal function of chronic kidney disease. Because this small molecule can effectively reduce blood uric acid, it also has the potential to treat hyperuricemia. No obvious toxic and side effects of small molecule N-methyl dodecylamine were found in the present invention, so it has good clinical application prospects. Summary of the invention

[0004] The purpose of the present invention is to provide an application of small molecule N-methyldodecylamine in the preparation of drugs for preventing and treating chronic kidney disease and hyperuricemia.

[0005] The invention discloses an application of a small molecule N-methyldodecylamine in the preparation of a drug for preventing and treating chronic kidney disease and hyperuricemia. The structural formula of the N-methyldodecylamine is as follows: .

[0006] The N-methyldodecylamine is the main active ingredient in drugs for preventing and treating chronic kidney disease and hyperuricemia.

[0007] The N-methyldodecylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the N-methyldodecylamine as an active ingredient is added with pharmaceutically acceptable adjuvants to prepare a pharmaceutically acceptable dosage form. The adjuvants include at least one of a diluent, an excipient, a binder, a surfactant, and an antioxidant. The dosage form includes an injection, a tablet, a capsule, a granule, a suspension, a sustained-release agent, and a pill.

[0008] The N-methyldodecylamine has the effect of significantly reducing serum creatinine and blood urea nitrogen of chronic kidney disease. The N-methyldodecylamine has the effect of reducing the mean urine protein in urine of chronic kidney disease and the mean uric acid in serum. The N-methyldodecylamine has the effect of improving kidney function and hyperuricemia in chronic kidney disease. Chronic kidney disease is chronic kidney disease caused by adenine.

[0009] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides the use of N-methyldodecylamine in the preparation of prevention and treatment of chronic kidney disease and hyperuricemia. The present invention uses adenine to construct a mouse chronic kidney disease model, and detects the renal function of the mouse by detecting biochemical indicators such as urine protein, blood urea nitrogen, serum creatinine, etc. It is proved that N-methyldodecylamine can improve the renal function of mice with chronic kidney disease caused by adenine, and can also reduce uric acid. It has small toxic and side effects and has a significant effect on the prevention and treatment of chronic kidney disease and hyperuricemia. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is the effect of adenine on the urine protein concentration in the normal control group (Control) and model group (Model, M) mice.

[0011] Figure 2 This study shows the effect of adenine on the serum urea nitrogen concentration in the normal control group and model group mice.

[0012] Figure 3 This is the effect of adenine on the serum creatinine concentration of mice in the normal control group and the model group.

[0013] Figure 4 This study is the effect of oral administration of small molecule N-methyldodecylamine (N) on the urine protein concentration in the normal control group, model group and M+N (2 mg / kg) group mice.

[0014] Figure 5 This is the effect of oral administration of small molecule N-methyldodecylamine on the urea nitrogen concentration in the serum of mice in the normal control group, model group and M+N (2 mg / kg) group.

[0015] Figure 6 This is the effect of oral administration of small molecule N-methyldodecylamine on the serum creatinine concentration of mice in the normal control group, model group and M+N (2 mg / kg) group.

[0016] Figure 7 This is the effect of oral administration of small molecule N-methyldodecylamine on the serum uric acid concentration of mice in the normal control group, model group and M+N (2 mg / kg) group. DETAILED DESCRIPTION

[0017] In order to make the technical means realized by the present invention easy to understand, the present invention is further explained below in conjunction with specific embodiments, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without making creative work are all within the scope of protection of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products unless otherwise specified, and their sources are not specifically limited. Example

[0018] The present invention provides an application of a small molecule N-methyldodecylamine in the preparation of a drug for preventing and treating chronic kidney disease and hyperuricemia. The structural formula of N-methyldodecylamine is as follows: The following is a further verification test on the application of N-methyldodecylamine in the preparation of drugs for the prevention and treatment of chronic kidney disease and hyperuricemia.

[0019] 1. Establishment of chronic kidney disease model and hyperuricemia model (1) Model establishment Ten healthy male Kunming mice aged 6-8 weeks and weighing 18-22 g were randomly divided into two groups according to their body weight: a normal control group of 4 mice and a model group of 6 mice.

[0020] 1) Normal control group (Control, 0.5% CMC-Na, n=4); 2) Model group (Adenine 100 mg / kg / d, n=6); The normal control group mice were gavaged with 0.5% sodium carboxymethylcellulose (CMC-Na) solution every morning, and the model group mice were gavaged with 100 mg / kg adenine and 0.5% CMC-Na suspension every morning for 5 weeks. During the modeling period, the mice were given sufficient food and water, and the body weight, drinking water and diet of the mice were recorded every day.

[0021] (2) Detection model After 5 weeks of continuous modeling, the mice were fasted but not watered for 8 hours, and the mice were placed in metabolic cages to collect urine. Blood was then collected from the inner canthus of the mice's eyes. The collected urine was centrifuged (860 g, 4°C, 10 min) and the supernatant was taken. The blood was centrifuged (1520 g, 4°C, 15 min) and the supernatant was taken for subsequent experiments.

[0022] In basic medical research and clinical practice, serum creatinine, blood urea nitrogen and urine protein are routinely used as standard and reliable indicators of glomerular filtration rate. Therefore, in order to test whether adenine can successfully establish a chronic kidney disease model, the serum creatinine, serum urea nitrogen and urine protein concentrations of mice were tested.

[0023] (3) Data processing The experimental data were statistically analyzed using Prism GraphPad 9.0 software. express, p <0.05 indicated that the difference between the groups was statistically significant.

[0024] (4) Experimental results The effects of adenine on the concentrations of urine protein, serum urea nitrogen, and serum creatinine in mice after 5 weeks of modeling were as follows: Figure 1 , Figure 2 , Figure 3 As shown in Figure 2, compared with the normal control group, the urine protein, serum urea nitrogen, and serum creatinine concentrations in the model group were significantly increased ( p <0.05), which proved that adenine-induced chronic kidney disease had obvious renal function damage, indicating that the chronic kidney disease model was successfully modeled.

[0025] 2. Effect verification (1) Grouping The 6 mice with successful modeling were divided into a model group and a small molecule group, with 3 mice in each group, as follows: 1) Model group (Adenine 100 mg / kg / d, n=3); 2) model and small molecule group (M+N, 2 mg / kg, n=3); 3) Normal control group (Control, n=4); After the model was successfully established, the drug was administered every other day. The model group was gavaged with adenine (100 mg / kg) and 0.5% CMC-Na suspension in the morning; the model and small molecule groups were gavaged with adenine (100 mg / kg) and 0.5% CMC-Na suspension in the morning, and N-methyldodecylamine (2 mg / kg) and double distilled water suspension in the afternoon; the normal control group was gavaged with 0.5% sodium carboxymethylcellulose solution in the morning. After 14 consecutive days of gavage, the mice were fasted for 8 hours but not water, and the mice were placed in metabolic cages to collect mouse urine. After that, blood was collected from the inner canthus of the mouse eyes, and the collected urine was centrifuged in a centrifuge (860 g, 4°C, 10 min) and the supernatant was taken. The blood was centrifuged in a centrifuge (1520 g, 4°C, 15 min) and the supernatant was taken to detect the urine protein concentration in urine and the urea nitrogen and creatinine concentrations in serum.

[0026] (2) Data processing The experimental data were statistically analyzed using Prism GraphPad 9.0 software. express, p <0.05 indicated that the difference between the groups was statistically significant.

[0027] (3) Experimental results The effects of N-methyldodecylamine on urine protein, serum urea nitrogen, and serum creatinine concentrations in mice are as follows: Figure 4 , Figure 5 , Figure 6 As shown, compared with the model group, the serum urea nitrogen and serum creatinine in the group given small molecule N-methyldodecylamine were significantly reduced ( p <0.05), the mean urine protein decreased. Because excessive intake of adenine can also lead to increased uric acid, we tested the uric acid concentration in serum, such as Figure 7 As shown, compared with the model group, the mean uric acid level in the group given small molecule N-methyldodecylamine was lower.

[0028] In summary, the small molecule N-methyl dodecylamine of the present invention can significantly reduce renal function related indicators such as serum creatinine and serum urea nitrogen in the chronic kidney disease model caused by adenine, reduce the mean urine protein in urine, and can effectively improve the renal function of chronic kidney disease. In addition, the mean uric acid in serum can be reduced to provide candidate molecules for the clinical treatment of chronic kidney disease and hyperuricemia. Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention, and those of ordinary skill in the art simply modify or replace the technical solution of the present invention with equivalents, without departing from the essence and scope of the technical solution of the present invention.

Claims

1. Use of a small molecule N-methyldodecylamine in the preparation of a drug for preventing and treating chronic kidney disease and hyperuricemia, characterized in that: The structural formula of N-methyldodecylamine is as follows: 。 2. The use according to claim 1, characterized in that: The N-methyldodecylamine is used as the main active ingredient of drugs for chronic kidney disease and hyperuricemia.

3. The use according to claim 1, characterized in that: The N-methyldodecylamine, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the N-methyldodecylamine as an active ingredient is added with pharmaceutically acceptable excipients to prepare a pharmaceutically acceptable dosage form.

4. The use according to claim 3, characterized in that: The auxiliary materials include at least one of a diluent, an excipient, a binder, a surfactant and an antioxidant.

5. The use according to claim 3, characterized in that: The dosage forms include injections, tablets, capsules, granules, suspensions, sustained-release preparations, and pills.

6. The use according to claim 1, characterized in that: The N-methyldodecylamine prevents and treats chronic kidney disease by reducing serum creatinine and blood urea nitrogen.

7. The use according to claim 1, characterized in that: The N-methyldodecylamine prevents and treats chronic kidney disease by reducing the mean urine protein in urine.

8. The use according to claim 1, characterized in that: The N-methyldodecylamine prevents and treats chronic kidney disease and hyperuricemia by lowering the mean uric acid level in serum.

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