CN-121971419-A - Application of spermidine and pharmaceutically acceptable salt thereof in preparation of DKD (DKD) treatment drugs

Abstract

The invention discloses application of spermidine and pharmaceutically acceptable salt thereof in preparing a medicine for treating DKD, which can obviously reduce UACR, show a dose-dependent trend, improve kidney function indexes, reduce blood sugar level, improve kidney histopathological changes, thereby reducing kidney injury related to diabetic nephropathy and delaying disease progression.

Inventors

• ZHAO TINGTING
• Duan Shiru

Assignees

• 中日友好医院(中日友好临床医学研究所)

Dates

Publication Date

20260505

Application Date

20260331

Claims (10)

1. 1. Use of spermidine in the preparation of a medicament for the treatment of DKD.
2. 2. Use of a pharmaceutically acceptable salt of spermidine in the preparation of a medicament for the treatment of DKD.
3. 3. Use of spermidine according to claim 1 or 2 for the preparation of a medicament for the treatment of DKD, characterized by reducing the urinary albumin/creatinine ratio, improving blood creatinine, improving blood urea nitrogen, reducing blood glucose levels, alleviating renal histopathological damage.
4. 4. The use of spermidine according to claim 3 for the preparation of a medicament for the treatment of DKD, characterized in that the diabetic nephropathy comprises diabetic nephropathy accompanied by elevated proteinuria and/or impaired renal function.
5. 5. The use of spermidine according to claim 4, in the manufacture of a medicament for the treatment of DKD, wherein the medicament is an oral formulation.
6. 6. The use of spermidine according to claim 5 for the preparation of a medicament for the treatment of DKD, wherein spermidine is administered at a dose of 1.25-5 mg/kg by weight.
7. 7. The use of spermidine according to claim 6, wherein the course of administration is 16 weeks.
8. 8. The method according to claim 1 to 7, wherein the drug is used in combination with one or more drugs selected from SGLT2 inhibitors, RAAS system inhibitors and metformin to prepare a combination drug or a compound preparation for treating diabetic nephropathy.
9. 9. The method of claim 8, wherein the SGLT2 inhibitor is dapagliflozin, engliflozin, canagliflozin or Multi-glibenclamide Ai Ting.
10. 10. The method according to claim 9, wherein the combination of spermidine and dapagliflozin is administered simultaneously, sequentially or in a fixed dose compound preparation for treating diabetic nephropathy patients with insufficient response to single SGLT2 inhibitors.

Description

Application of spermidine and pharmaceutically acceptable salt thereof in preparation of DKD (DKD) treatment drugs Technical Field The invention relates to the technical field of biological medicines, in particular to application of spermidine and pharmaceutically acceptable salts thereof in preparation of a medicine for treating DKD. Background Diabetic nephropathy (Diabetic KIDNEY DISEASE, DKD) is one of the most common and serious microvascular complications of diabetes, and is also a significant cause of chronic kidney disease and end stage renal disease. Clinical manifestations of DKD include persistent albuminuria, reduced glomerular filtration rate and progressive renal failure, often accompanied by metabolic disorders and poor glycemic control. Current clinical therapies mainly include glycemic control, blood pressure management, inhibitors of the renin-angiotensin system (RASi), inhibitors of sodium-glucose co-transporter 2 (SGLT 2 i), and the like, but still a significant proportion of patients continue to progress under standard therapy. The following problems are mainly existed: 1) Some patients have inadequate proteinuria control; 2) Renal function continues to decline; 3) There is still limited overall benefit to the combined metabolic disorder/hyperglycemia. Therefore, there is a need to develop new interventions capable of improving proteinuria, renal function and metabolic abnormalities simultaneously. Disclosure of Invention In order to overcome the defects of the prior art, the invention aims to provide the application of spermidine and pharmaceutically acceptable salts thereof in preparing the DKD medicament, which can obviously reduce UACR, show a dose-dependent trend, improve kidney function indexes, reduce blood sugar level, improve kidney histopathological changes and reduce renal tubular injury scores, thereby reducing kidney injury related to diabetic nephropathy and delaying disease progression. The technical scheme of the invention is that spermidine is used for preparing the DKD medicine. Also provided is the use of a pharmaceutically acceptable salt of spermidine in the manufacture of a medicament for the treatment of DKD. Still further, spermidine and its pharmaceutically acceptable salts reduce urinary albumin/creatinine ratio, improve blood creatinine, improve blood urea nitrogen, reduce blood glucose levels, and alleviate renal histopathological injury. Still further, the diabetic nephropathy includes diabetic nephropathy accompanied by elevated proteinuria and/or impaired renal function. Further, the medicament is an oral preparation. Furthermore, the dosage of spermidine is 1.25-5 mg/kg based on the weight of the body. Still further, the administration period is 16 weeks. Further, the medicament is used for being combined with one or more medicaments selected from SGLT2 inhibitors, RAAS system inhibitors and metformin to prepare a combined medicament or a compound preparation for treating diabetic nephropathy. Still further, the SGLT2 inhibitor is dapagliflozin, engagliflozin, canagliflozin, or multi-gliptin Ai Ting. Furthermore, the combined use refers to simultaneous administration, sequential administration or preparation of fixed-dose compound preparation of spermidine and dapagliflozin, and the compound preparation is used for treating diabetic nephropathy patients with insufficient response to single SGLT2 inhibitor. The beneficial technical effects of the invention are as follows: 1. UACR was significantly reduced and had a dose-dependent trend. 2. Improving related indexes of kidney functions such as Scr, BUN and the like. 3. Lowering blood glucose levels. 4. Improving renal histopathological changes and reducing tubular injury scores. 5. Reduce kidney injury associated with diabetic nephropathy and delay disease progression. Drawings Figure 1 shows the urinary albumin/creatinine ratio (UACR) of rats from different treatment groups. The injection is Sham, DKD, a diabetic nephropathy model, spdL, a low-dose spermidine intervention group, spdM, a medium-dose spermidine intervention group, spdH, a high-dose spermidine intervention group, and DAPA, dapagliflozin positive control group. Data are presented as mean ± SEM. Compared to Sham group, # # P < 0.0001, # # P <0.01, # P < 0.0001 compared to DKD group. Fig. 2 shows kidney function related indicators for rats of different treatment groups. (A) Blood Urea Nitrogen (BUN) levels in rats of each group. (B) blood creatinine (Scr) levels in each group of rats. The injection is Sham, DKD, a diabetic nephropathy model, spdL, a low-dose spermidine intervention group, spdM, a medium-dose spermidine intervention group, spdH, a high-dose spermidine intervention group, and DAPA, dapagliflozin positive control group. Data are presented as mean ± SEM. Compared with Sham group, # P < 0.01, # P < 0.0001, # P < 0.05, # P < 0.01 compared with DKD group. Fig. 3 shows the change in blood glucose levels for rats from different treatment