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Application of YM-155 in medicine for preventing and treating chronic kidney disease

A YM-155 technology for chronic kidney disease, applied in the field of medicine, can solve the problems of lack of intervention methods, achieve the effect of improving chronic kidney disease, inhibiting the transdifferentiation of renal tubular epithelial cells, and inhibiting the activation of

Pending Publication Date: 2022-03-15
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the nephrology community has extensively explored the pathogenesis and intervention strategies of CKD, there is still a lack of satisfactory intervention methods in clinical practice. A considerable number of CKD patients eventually develop end-stage renal disease (ESRD) and need to rely on Renal replacement therapy to sustain life places a heavy burden on families and society
There are no reports of YM-155 being used in the treatment of chronic kidney disease

Method used

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  • Application of YM-155 in medicine for preventing and treating chronic kidney disease
  • Application of YM-155 in medicine for preventing and treating chronic kidney disease
  • Application of YM-155 in medicine for preventing and treating chronic kidney disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Prove that the therapeutic dose of YM-155 (3mg / kg) has no toxic side effects on normal mice:

[0022] 1. Experimental materials and methods:

[0023] The C57BL / 6 species male mice used in this example (7 weeks old at the time of purchase, weighing 20-24 g) were purchased from the Experimental Animal Center of Nanjing Medical University, and were raised in an SPF-level barrier environment in the Experimental Animal Center of Nanjing Medical University. Feed, maintain a 12h / 12h light / dark rhythm. Laboratory temperature: 20-25°C, humidity 50±5%. The mice were randomly divided into control group and YM-155 group after 1 week of adaptive feeding.

[0024] The YM-155 used in this example was purchased from Selleck Company. The dosage of the mice was 3mg / kg, and the administration method was intraperitoneal injection; Administration for 15 days. The whole blood of the mice was collected 2 hours after the last administration, and the serum was obtained by centrifugation at ...

Embodiment 2

[0029] A therapeutic dose of YM-155 (3mg / kg) improves the levels of inflammatory factors in the kidney tissue of the mouse UUO model:

[0030] 1. Experimental materials and methods:

[0031] 1.1. Establishment of unilateral ureteral obstruction (UUO) model and drug treatment:

[0032] Forty male C57BL / 6 mice (7 weeks old at the time of purchase, weighing 20-24 g) were bred in an SPF-grade barrier environment in the Experimental Animal Center of Nanjing Medical University. After adaptive feeding for 1 week, the mice were randomly divided into Vehicle+Sham group, Vehicle+UUO group, YM-155+Sham group, and YM155+UUO group.

[0033] After grouping, the mice in each group received two intraperitoneal injections of vehicle or YM-155 (3mg / kg) 24h and 2h before the UUO model respectively. Afterwards, unilateral ureteral ligation causes obstruction of the renal drainage system on the obstructed side, induces chronic renal structural damage, and simulates clinical renal interstitial fi...

Embodiment 3

[0043] Therapeutic doses of YM-155 (3mg / kg) ameliorate renal pathological damage in the mouse UUO model:

[0044] 1. Experimental materials and methods:

[0045] Vehicle+Sham group, Vehicle+UUO group, YM-155+Sham group, YM-155+UUO group mouse modeling and administration methods were the same as in Example 2. After the last administration, the mice were sacrificed, and the left kidney tissue of Sham mice and the affected kidney tissue of UUO mice were taken, fixed with 4% paraformaldehyde at room temperature for 24 hours, dehydrated, embedded in paraffin and sectioned for Masson staining. Masson staining of kidney tissue was performed using the Masson trichrome staining solution kit from Servicebio. Use Image-ProPlus (Version 6.0.0.260) software to statistically analyze the area of ​​Masson-stained collagen fibers. Data are represented using mean ± SEM. Analysis of variance (ANOVA) was used for comparison between multiple groups, and T test was used for data comparison betwe...

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Abstract

The invention provides an application of YM-155 (Sepantrone Bromide) in a medicine for preventing and treating chronic kidney diseases, which is characterized in that the YM-155 (Sepantrone Bromide) can relieve the kidney inflammation level and pathological injury of the chronic kidney diseases and is used for preparing the medicine for preventing and treating the chronic kidney diseases; the YM-155 can be used for preparing a medicine for inhibiting the activation of renal interstitial fibroblasts. The YM-155 can be used for preparing a medicine for inhibiting the transformation of renal tubular epithelial cells to myofibroblasts. The invention finds and proves that YM-155 can inhibit and reduce the renal inflammation level and fibrosis degree of renal interstitial fibrosis model mice, inhibit the activation of renal interstitial fibroblasts and the conversion of renal tubular epithelial cells to myofibroblasts, and can be a potential chronic kidney disease prevention and treatment medicine. YM-155 is applied to medicines, so that the effect of improving chronic kidney diseases can be achieved, and good development and application prospects are achieved.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of YM-155 (Sepantronium Bromide) in the prevention and treatment of chronic kidney disease. Background technique [0002] In recent years, with the change of lifestyle, the incidence of chronic kidney disease (CKD) has increased year by year. According to the results of epidemiological survey, the global incidence of CKD is as high as 10%. Based on this, it is estimated that about 7 billion CKD patients. Therefore, CKD has become a worldwide public health problem. Although the nephrology community has extensively explored the pathogenesis and intervention strategies of CKD, there is still a lack of satisfactory intervention methods in clinical practice. A considerable number of CKD patients eventually develop end-stage renal disease (ESRD) and need to rely on Renal replacement therapy to maintain life has brought a heavy burden to families and society. [0003] Renal in...

Claims

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Application Information

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IPC IPC(8): A61K31/497A61P13/12
CPCA61K31/497A61P13/12
Inventor 吴梦秋张爱华贾占军金倩倩陈维宜顾然李宇婷张凌歌
Owner NANJING CHILDRENS HOSPITAL
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