Use of a pharmaceutical composition containing curculigoside in treating drugs for type 2 diabetic nephropathy

Abstract

This invention discloses the application of a pharmaceutical composition containing curculigoside in the treatment of type 2 diabetic nephropathy, belonging to the technical field of diabetic nephropathy drugs. The pharmaceutical composition uses curculigoside and astragaloside A as active ingredients, and also includes pharmaceutically acceptable excipients, wherein the mass ratio of curculigoside to astragaloside A is 1:0.2 to 1:1.5. This invention is the first to apply curculigoside to the treatment of type 2 diabetic nephropathy. Through the synergistic effect of curculigoside and astragaloside A, it can significantly improve renal function in patients with type 2 diabetic nephropathy, inhibit inflammatory responses and oxidative stress, reduce renal pathological damage, and delay the progression of renal fibrosis. Furthermore, the pharmaceutical composition has high safety, no obvious adverse reactions, diverse dosage forms, and high medication adherence, overcoming the shortcomings of existing therapeutic drugs with limited efficacy and numerous adverse reactions, and has significant clinical value and broad application prospects.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology for diabetic nephropathy, and in particular to the use of pharmaceutical compositions containing curculigoside in the treatment of type 2 diabetic nephropathy. Background Technology

[0002] Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes and the leading cause of end-stage renal disease. Its pathological features are mainly glomerular mesangial proliferation, basement membrane thickening, and renal interstitial fibrosis. Clinically, it is often accompanied by renal function impairment manifestations such as proteinuria, elevated serum creatinine, and elevated blood urea nitrogen, which seriously threaten the patient's life and health.

[0003] Currently, the main drugs used in clinical treatment of diabetic nephropathy include hypoglycemic drugs, antihypertensive drugs, and statins. Metformin, a commonly used hypoglycemic drug, can control blood sugar, but its protective effect on renal function in diabetic nephropathy is limited, and long-term use can easily cause adverse reactions such as gastrointestinal reactions and liver and kidney damage. Other drugs, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, mainly delay the progression of kidney disease by lowering blood pressure, but cannot fundamentally improve the pathological damage to the kidneys, and the treatment effect is not ideal.

[0004] Curculigoside is a natural active ingredient extracted from the plant Curculigo orchioides. Existing research shows that it has pharmacological effects such as anti-inflammatory, antioxidant, and immunomodulatory effects. It is mainly used in the treatment of diseases such as osteoporosis and menopausal syndrome. There are no reports on the application of curculigoside in the treatment of diabetic nephropathy, nor have there been any technical solutions for the treatment of diabetic nephropathy by combining curculigoside with other ingredients.

[0005] Astragaloside A is an active ingredient extracted from the legume Astragalus membranaceus. It has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, and promoting diuresis and reducing edema. Current research shows that it has a certain protective effect on the kidneys. However, the effect of using astragaloside A alone to treat diabetic nephropathy is limited and cannot meet the needs of clinical treatment.

[0006] Based on this, developing a drug composition that is highly effective and safe, and can improve renal function damage and slow disease progression in diabetic nephropathy through multiple targets and pathways, has significant clinical value and application prospects. Summary of the Invention

[0007] In view of the shortcomings of existing drugs for the treatment of type 2 diabetic nephropathy, such as limited efficacy and numerous adverse reactions, this invention provides a pharmaceutical composition containing curculigoside for the treatment of type 2 diabetic nephropathy. Through the synergistic effect of curculigoside and astragaloside A, this pharmaceutical composition can significantly improve renal function in patients with type 2 diabetic nephropathy, inhibit inflammatory response and oxidative stress, delay the progression of renal fibrosis, and has high safety, making it suitable for long-term use.

[0008] To achieve the above objectives, the present invention provides the application of a pharmaceutical composition containing curculigoside in a treatment for type 2 diabetic nephropathy. The pharmaceutical composition uses curculigoside and astragaloside A as active ingredients and also includes pharmaceutically acceptable excipients. The mass ratio of curculigoside to astragaloside A is 1:0.2 to 1:1.5.

[0009] Preferably, the mass ratio of curculigoside to astragaloside A is 1:0.5 to 1:1.2.

[0010] Preferably, the total mass of cyclophosphamide and astragaloside A in the pharmaceutical composition accounts for 10% to 50% of the total mass of the pharmaceutical composition.

[0011] Preferably, the total mass of cyclophosphamide and astragaloside A in the pharmaceutical composition accounts for 20% to 40% of the total mass of the pharmaceutical composition.

[0012] Preferably, pharmaceutically acceptable excipients are selected from one or more of fillers, disintegrants, binders, lubricants, and solubilizers.

[0013] Preferably, the dosage form of the pharmaceutical composition is an oral dosage form or an injectable dosage form; the oral dosage form is selected from tablets, capsules, granules, oral liquids, and powders; the injectable dosage form is selected from injection solutions and lyophilized powder injections.

[0014] Therefore, the application of the pharmaceutical composition containing curculigoside of the present invention in the treatment of type 2 diabetic nephropathy has the following beneficial effects: (1) This invention is the first to apply curculigoside to the treatment of type 2 diabetic nephropathy, filling the technical gap of curculigoside in this field. By combining curculigoside and astragaloside A in a specific ratio, a significant synergistic effect is produced, and its therapeutic effect is significantly better than that of curculigoside alone, astragaloside A alone, and metformin, a commonly used clinical drug.

[0015] (2) The pharmaceutical composition of the present invention can exert therapeutic effects from multiple targets and multiple pathways. It can significantly improve the renal function of patients with type 2 diabetic nephropathy (reduce the urinary albumin excretion rate, serum creatinine, and blood urea nitrogen levels), enhance the body's antioxidant capacity (increase superoxide dismutase activity and reduce malondialdehyde content), inhibit inflammatory response (reduce interleukin-6 and tumor necrosis factor-α levels), reduce kidney pathological damage, delay the process of renal fibrosis, and fundamentally improve the condition of type 2 diabetic nephropathy.

[0016] (3) The preparation process of the drug composition of the present invention is simple, the active ingredients used are of high purity and the excipients are safe. There are no obvious adverse reactions after administration, and it is non-toxic to important organs such as the liver and heart. It is safe and suitable for long-term use, which solves the problems of many adverse reactions and poor safety of existing therapeutic drugs.

[0017] (4) The drug composition of the present invention has a variety of dosage forms and can be prepared into oral or injectable dosage forms according to clinical needs. It is applicable to a wide range of people, has high medication compliance, and has important clinical value and broad application prospects.

[0018] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 The result is the urine albumin excretion rate test result; Figure 2 The results are from serum Scr testing. Figure 3 This refers to the serum BUN test results; Figure 4 The results are for serum SOD activity assay. Figure 5 The results are for the detection of serum MDA levels; Figure 6 The results of inflammatory factor index detection in rats of each group are shown. Detailed Implementation

[0021] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0022] To make the objectives, technical solutions, and advantages of this application clearer, more thorough, and more complete, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings and embodiments. The following detailed descriptions are all illustrations of embodiments, intended to provide further detailed explanation of the present invention. Unless otherwise specified, all technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0023] In the following examples, cyclophosphamide (97% purity) and astragaloside A (95% purity) were purchased from Shaanxi Huike Plant Development Co., Ltd.; excipients such as microcrystalline cellulose, sodium carboxymethyl starch, hydroxypropyl methylcellulose, and magnesium stearate were all commercially available pharmaceutical-grade products; reagents used in the experiments were all purchased from Nanjing Jiancheng Bioengineering Institute, and instruments were all conventional laboratory instruments.

[0024] Example 1 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, astragaloside A (95% purity) 40g, microcrystalline cellulose 200g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0025] Preparation method: Mix curculigoside, astragaloside A, microcrystalline cellulose, and sodium carboxymethyl starch evenly, add hydroxypropyl methylcellulose aqueous solution (concentration 5%) as a binder, granulate, dry, granulate, add magnesium stearate and mix evenly, compress into tablets to obtain tablets, each tablet containing 50mg curculigoside and 40mg astragaloside A (mass ratio of curculigoside to astragaloside A 1:0.8).

[0026] Example 2 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, astragaloside A (95% purity) 25g, microcrystalline cellulose 220g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 15g.

[0027] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside and 25mg of astragaloside A (mass ratio of curculigoside to astragaloside A 1:0.5).

[0028] Example 3 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, astragaloside A (95% purity) 60g, microcrystalline cellulose 190g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0029] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside and 60mg of astragaloside A (mass ratio of curculigoside to astragaloside A 1:1.2).

[0030] Example 4 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 60g, astragaloside A (95% purity) 60g, microcrystalline cellulose 180g, sodium carboxymethyl starch 20g, hydroxypropyl methylcellulose 15g, and magnesium stearate 5g.

[0031] Preparation method: Mix curculigoside, astragaloside A, microcrystalline cellulose and sodium carboxymethyl starch evenly, add hydroxypropyl methylcellulose aqueous solution (concentration 5%) to granulate, dry, granulate, add magnesium stearate and mix evenly, fill into capsules to obtain capsules, each capsule contains 60mg curculigoside and 60mg astragaloside A (mass ratio of curculigoside to astragaloside A 1:1).

[0032] Example 5 The pharmaceutical composition containing curculigoside has the following formula (per 1000 sachets, 1g per sachet): curculigoside (97% purity) 80g, astragaloside A (95% purity) 72g, lactose 600g, sodium carboxymethyl starch 40g, povidone 30g, and steviol glycoside 8g.

[0033] Preparation method: Mix curculigoside, astragaloside A, lactose and sodium carboxymethyl starch evenly, add povidone aqueous solution (concentration 10%) to granulate, dry, granulate, add steviol glycoside and mix evenly, package in bags to obtain granules, each bag contains 80mg curculigoside and 72mg astragaloside A (mass ratio of curculigoside to astragaloside A 1:0.9).

[0034] Example 6 The pharmaceutical composition containing curculigoside has the following formula (per 1000mL): curculigoside (97% purity) 5g, astragaloside A (95% purity) 2.5g, sodium chloride 9g, and water for injection to 1000mL.

[0035] Preparation method: Add curculigoside, astragaloside A, and sodium chloride to an appropriate amount of water for injection, stir to dissolve, adjust the pH to 6.5~7.5, add water for injection to make up to 1000mL, filter, fill and sterilize to obtain the injection solution, each ml contains 5mg curculigoside and 2.5mg astragaloside A (mass ratio of curculigoside to astragaloside A 1:0.5).

[0036] Example 7 The pharmaceutical composition containing curculigoside has the following formula (per 1000 vials): curculigoside (97% purity) 10g, astragaloside A (95% purity) 15g, mannitol 80g, and water for injection to 1000mL.

[0037] Preparation method: Add curculigoside, astragaloside A, and mannitol to an appropriate amount of water for injection, stir to dissolve, adjust the pH to 6.5~7.5, add water for injection to make up to 1000mL, filter, dispense, freeze dry, stopper, and cap to obtain lyophilized powder for injection. Each vial contains 10mg curculigoside and 15mg astragaloside A (mass ratio of curculigoside to astragaloside A is 1:1.5).

[0038] Comparative Example 1 The formula for a single cyclophosphamide preparation (per 1000 tablets, 0.5g per tablet) is as follows: cyclophosphamide (97% purity) 50g, microcrystalline cellulose 240g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0039] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside.

[0040] Comparative Example 2 Astragaloside A preparation, formula (per 1000 tablets, 0.5g per tablet): Astragaloside A (purity 95%) 40g, microcrystalline cellulose 240g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, magnesium stearate 10g.

[0041] Preparation method: Same as in Example 1, each tablet contains 40mg of astragaloside A.

[0042] Comparative Example 3 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, astragaloside A (95% purity) 10g, microcrystalline cellulose 270g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0043] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside and 10mg of astragaloside A, with a mass ratio of curculigoside to astragaloside A of 1:0.2.

[0044] Comparative Example 4 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, astragaloside A (95% purity) 80g, microcrystalline cellulose 160g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0045] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside and 80mg of astragaloside A, with a mass ratio of curculigoside to astragaloside A of 1:1.6.

[0046] Comparative Example 5 The pharmaceutical composition containing curculigoside has the following formula (per 1000 tablets, 0.5g per tablet): curculigoside (97% purity) 50g, tanshinone IIA 40g, microcrystalline cellulose 200g, sodium carboxymethyl starch 30g, hydroxypropyl methylcellulose 20g, and magnesium stearate 10g.

[0047] Preparation method: Same as in Example 1, each tablet contains 50mg of curculigoside and 40mg of tanshinone IIA.

[0048] Test case Laboratory animals: SPF-grade male SD rats, 6-8 weeks old, weighing 200±20g, were housed in an SPF-grade animal room at an ambient temperature of 22±2℃ and a relative humidity of 55±5%, with a 12h light / dark cycle and free access to food and water. They were used for experiments after acclimatization for one week.

[0049] Test drugs: the pharmaceutical compositions prepared in Examples 1-7, the formulations prepared in Comparative Examples 1-5, and the commercially available metformin tablets, each weighing 0.5g, were used as clinical control drugs.

[0050] After one week of acclimatization, rats were randomly divided into a normal control group (n=10) and a model group (n=90). Rats in the model group were fasted for 12 hours and then intraperitoneally injected with STZ solution (60 mg / kg, prepared with 0.1 mol / L citrate buffer, pH=4.5), while the normal control group received an equal volume of citrate buffer. Blood was collected from the tail vein 72 hours after injection to measure fasting plasma glucose (FPG). A FPG ≥ 16.7 mmol / L was considered a successful diabetes model.

[0051] Diabetic model rats were fed a high-sugar, high-fat diet for 8 weeks. Urinary albumin excretion rate, serum creatinine, and blood urea nitrogen were measured. Rats with urinary albumin excretion rate ≥30mg / 24h, serum creatinine ≥100μmol / L, and blood urea nitrogen ≥8mmol / L were considered to have successfully established a diabetic nephropathy model. A total of 72 successful model rats were obtained and randomly divided into 12 groups of 6 rats each: Example 1-7, Comparative Example 1-5, and Clinical Control Group. A normal control group (10 rats) was also set up.

[0052] Rats in each group were administered the drug according to their body weight, once daily for 8 consecutive weeks. The specific dosages are as follows: Normal control group: physiological saline, administered by gavage, dose 10 mL / kg; Examples 1-7: The pharmaceutical compositions prepared in the corresponding examples were administered by gavage (tablets, capsules, granules) or intraperitoneal injection (injection solution, lyophilized powder for injection), with a dosage of 50 mg / kg based on curculigoside. Comparative Example 1: Single preparation of curculigoside, administered by gavage at a dose of 50 mg / kg (calculated as curculigoside); Comparative Example 2: Astragaloside A preparation, administered by gavage, with a dosage of 40 mg / kg (consistent with the dosage of astragaloside A in Example 1). Comparative Examples 3-4: The drug compositions prepared in the corresponding examples were administered by gavage at a dose of 50 mg / kg, calculated as curculigoside. Comparative Example 5: The compound preparation of curculigoside and tanshinone IIA was administered by gavage at a dose of 50 mg / kg (calculated as curculigoside). Clinical control group: Metformin tablets were administered by gavage at a dose of 200 mg / kg.

[0053] (1) Observe the rats’ mental state, food intake, water intake, urine output and weight changes daily, and record the rat mortality.

[0054] The results showed that the normal control group rats were in good mental condition, with normal food intake, water intake, and urine output, and their weight gradually increased without any deaths. The model group (before drug administration) rats were lethargic, with reduced food intake, significantly increased water intake and urine output, and a significant decrease in weight. After 8 weeks of drug administration, the mental condition of rats in Examples 1-7 was significantly improved, with food intake, water intake, and urine output gradually returning to normal, and their weight slowly increasing without any deaths. The mental condition of rats in Comparative Examples 1-5 and the clinical control group was improved, but the degree of improvement was not as good as that in Examples 1-7. Among them, some rats in Comparative Examples 3-4 and Comparative Example 5 still had abnormal water intake and urine output, and one rat in the clinical control group died.

[0055] (2) Detection of renal function indicators: After 8 weeks of drug administration, the rats were fasted for 12 hours and urine was collected in the metabolic cage for 24 hours. The urine albumin excretion rate was detected by urine albumin detection kit. Blood was collected from the tail vein, centrifuged (3000 r / min, 10 min), and serum was separated. Serum Scr and BUN levels were detected by serum creatinine detection kit and blood urea nitrogen detection kit, respectively.

[0056] Results of renal function index detection in each group of rats Figure 1-3 And as shown in Table 1: Table 1 Results of renal function indicators in rats of each group

[0057] Note: Compared with the normal control group, P <0.05; # Compared with Example 1, P <0.05.

[0058] Table 1 shows that the renal function indicators of the normal control group rats were normal; the urinary albumin excretion rate, serum Scr, and BUN levels of the rats in Examples 1-7 were significantly lower than those of the control groups. PThe renal function of the present invention is significantly improved in rats with diabetic nephropathy (<0.05) and close to that of the normal control group. The renal function indicators of the groups in Examples 1-5 are better than those of the groups in Examples 6-7, indicating that the efficacy is better when the proportion of active ingredients is within the preferred range of the present invention. The renal function improvement effects of the comparative groups 1-2, 3-4, 5 and the clinical drug group are significantly worse than those of the groups in the examples of the present invention, indicating that the combination of cyclophosphamide and astragaloside A in a specific ratio can produce a significant synergistic effect, and the synergistic component is specific. The efficacy decreases after replacement.

[0059] (3) Detection of oxidative stress indicators: Rat serum was collected and the SOD activity and MDA content were detected by SOD detection kit and MDA detection kit, respectively.

[0060] The results of oxidative stress index detection in each group of rats are as follows: Figure 4-5 And as shown in Table 2: Table 2 Results of oxidative stress index detection in rats of each group

[0061] Note: Compared with the normal control group, P <0.05; # Compared with Example 1, P <0.05.

[0062] Table 2 shows that the normal control group rats had high serum SOD activity, low MDA content, and low oxidative stress level; the serum SOD activity of rats in Examples 1-7 was significantly higher than that of the control groups, and the MDA content was significantly lower than that of the control groups. P <0.05), indicating that the pharmaceutical composition of the present invention can significantly enhance the antioxidant capacity of diabetic nephropathy rats and reduce oxidative stress damage; the oxidative stress improvement effect of the groups in Examples 1-5 is better than that of the groups in Examples 6-7, further verifying the importance of the ratio of active ingredients; the antioxidant effect of each comparative group is inferior to that of the groups in the examples of the present invention, indicating that the synergistic effect of cyclophosphamide and astragaloside A can effectively enhance antioxidant capacity, and the same effect cannot be achieved by using a single ingredient or improper ratio, or by replacing the synergistic ingredient.

[0063] (4) Detection of inflammatory factors: Rat serum was collected and the serum IL-6 and TNF-α levels were detected using IL-6 detection kit and TNF-α detection kit, respectively.

[0064] The results of inflammatory factor marker detection in each group of rats are as follows: Figure 6 And as shown in Table 3: Table 3 Results of Detection of Inflammatory Factor Indicators in Each Group of Rats

[0065] Note: Compared with the normal control group, P <0.05; # Compared with Example 1, P <0.05.

[0066] Table 3 shows that the serum IL-6 and TNF-α levels in the normal control group rats were low, and the inflammatory response was mild; the serum IL-6 and TNF-α levels in groups 1-7 of Examples were significantly lower than those in the comparative groups and the clinical control group. P <0.05), indicating that the pharmaceutical composition of the present invention can significantly inhibit the inflammatory response in diabetic nephropathy rats. The levels of inflammatory factors in the groups of Examples 1-5 were lower than those in the groups of Examples 6-7, indicating that the anti-inflammatory effect is better when the active ingredients are compounded in the preferred ratio; the levels of inflammatory factors in each comparative group were significantly higher than those in the example groups, among which the anti-inflammatory inhibition effect of comparative groups 1-2 and the clinical control group was the worst, and the anti-inflammatory effect of comparative group 5 was also significantly worse than that of the example groups, further confirming that the synergistic effect of curculigoside and astragaloside A compounded in a specific ratio can effectively enhance the anti-inflammatory effect and reduce kidney inflammatory damage, and the synergistic component is specific and cannot be replaced by other components.

[0067] (5) Kidney pathological examination: Eight weeks after administration, rats were sacrificed, and both kidneys were removed. The kidney weight was measured, and the kidney index was calculated (kidney index = kidney weight / body weight × 100%). The right kidney was removed, fixed with 4% paraformaldehyde, embedded in paraffin, sectioned, stained with HE, and the pathological changes of the kidney tissue were observed under a microscope. The degree of kidney damage was assessed using the pathological scoring standard (0-4 points): 0 points = no damage; 1 point = slight damage, mild swelling of the glomeruli and a small amount of degeneration of the renal tubules; 2 points = moderate damage, moderate swelling of the glomeruli, mesangial proliferation, and moderate degeneration of the renal tubules; 3 points = severe damage, obvious swelling of the glomeruli, severe mesangial proliferation, and extensive degeneration and necrosis of the renal tubules; 4 points = very severe damage, glomerular fibrosis and extensive necrosis of the renal tubules.

[0068] The results of kidney pathological examination in each group of rats are shown in Table 4 below: Table 4. Pathological examination results of rat kidneys in each group

[0069] Note: Compared with the normal control group, P <0.05; # Compared with Example 1, P <0.05.

[0070] As shown in Table 4, the normal control group rats had normal kidney index, mild kidney pathological damage, and low pathological scores; the kidney index of rats in Examples 1-7 was significantly lower than that of the comparative groups and the clinical control group, and the pathological scores were also significantly lower than those of the comparative groups. P <0.05), and pathological section observation showed that the pathological damage such as glomerular swelling, mesangial proliferation, and renal tubular degeneration in the Example group was significantly less than that in the comparative groups, indicating that the pharmaceutical composition of the present invention can significantly reduce the pathological damage of the kidneys in diabetic nephropathy rats, reduce the kidney index, and delay the progression of renal fibrosis. The kidney index and pathological scores of Example 1-5 groups were lower than those of Example 6-7 groups, further verifying the superiority of the optimal ratio of active ingredients, indicating that when xiongruciformin and astragaloside A are combined in a ratio of 1:0.5 to 1:1.2, the effect on improving the pathological damage of the kidneys is the best. The pathological damage of the kidneys in each comparative group was more severe than that in the Example group, with the pathological damage in comparative group 1-2 being the most obvious. Although comparative group 6 showed some improvement, the effect was far less than that in the Example group, which again confirms that the synergistic effect of the two active ingredients in the pharmaceutical composition of the present invention is of great significance in reducing the pathological damage of the kidneys and delaying the progression of renal fibrosis.

[0071] (6) Safety testing: During the administration period, observe whether rats experience adverse reactions such as vomiting, diarrhea, and convulsions; 8 weeks after administration, detect the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in rats to assess the drug’s hepatotoxicity; take rat heart, liver, spleen, and lungs, stain with HE, observe histopathological changes, and assess the drug’s systemic safety.

[0072] The safety test results of each group of rats are shown in Table 5 below: Table 5. Safety test results of rats in each group

[0073] Note: Compared with the normal control group, P <0.05; # Compared with Example 1, P <0.05.

[0074] Table 5 shows that the serum ALT and AST levels of the normal control group rats were normal, with no adverse reactions and no pathological abnormalities in the organs; although the serum ALT and AST levels of the rats in Examples 1-7 were slightly higher than those of the normal control group, they were all within the normal physiological range and significantly lower than those of the comparative groups. PThe concentration of α-hydroxyl radical (α-hydroxyl radical) was <0.05%. No adverse reactions were observed during administration, and no pathological abnormalities were found in vital organs such as the heart, liver, spleen, and lungs, indicating that the pharmaceutical composition of this invention has high safety, is non-toxic to vital organs such as the liver, and is suitable for long-term use. Among the comparative groups, the clinical drug group had the worst safety profile, with rat deaths, adverse reactions, and liver pathological damage. Comparative groups 1-5 all showed varying degrees of adverse reactions, and serum ALT and AST levels were significantly elevated. This indicates that the pharmaceutical composition of this invention has superior safety compared to existing clinical drugs and preparations with single components, improper proportions, or substituted synergistic components, solving the problems of numerous adverse reactions and poor long-term safety of existing therapeutic drugs.

[0075] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. The use of a pharmaceutical composition containing curculigoside in the treatment of type 2 diabetic nephropathy, characterized in that: The pharmaceutical composition uses curculigoside and astragaloside A as active ingredients, and also includes pharmaceutically acceptable excipients; the mass ratio of curculigoside to astragaloside A is 1:0.2 to 1:1.

5.

2. The use of the pharmaceutical composition containing aphanamol in the treatment of type 2 diabetic nephropathy according to claim 1, characterized in that: The mass ratio of curculigoside to astragaloside A is 1:0.5 to 1:1.

2.

3. The use of the pharmaceutical composition containing aphanamol in the treatment of type 2 diabetic nephropathy according to claim 1, characterized in that: In the pharmaceutical composition, the total mass of xiongruciformin and astragaloside A accounts for 10% to 50% of the total mass of the pharmaceutical composition.

4. The use of the pharmaceutical composition containing aphanamol in the treatment of type 2 diabetic nephropathy according to claim 3, characterized in that: In the pharmaceutical composition, the total mass of xiongmaoside and astragaloside A accounts for 20% to 40% of the total mass of the pharmaceutical composition.

5. The use of the pharmaceutical composition containing aphanamol in the treatment of type 2 diabetic nephropathy according to claim 1, characterized in that: Pharmaceutically acceptable excipients are selected from one or more of the following: fillers, disintegrants, binders, lubricants, and solubilizers.

6. The use of the pharmaceutical composition containing aphanamol in the treatment of type 2 diabetic nephropathy according to claim 1, characterized in that: The dosage form of the pharmaceutical composition is an oral dosage form or an injectable dosage form; the oral dosage form is selected from one of tablets, capsules, granules, oral liquids, and powders; the injectable dosage form is selected from one of injection solutions and lyophilized powder injections.

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