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Application of Tauroursodeoxycholic acid (TUDCA)

A technology for tauroursodeoxycholic acid and acute kidney injury, applied in the new use field of tauroursodeoxycholic acid

Inactive Publication Date: 2018-09-28
THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the medicinal use of TUDCA in preventing the transition from AKI to CKD

Method used

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  • Application of Tauroursodeoxycholic acid (TUDCA)
  • Application of Tauroursodeoxycholic acid (TUDCA)
  • Application of Tauroursodeoxycholic acid (TUDCA)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] C57BL / 6 mice (male, 8-10 weeks old) were subjected to sham surgery or 30 min unilateral ischemia of the left kidney followed by reperfusion. At 2 or 7 or 14 days, kidney tissues were collected for biochemical and histological analysis (A, B, D, E, F, G, H, I). Right nephrectomy was performed on day 1, 6 or 13 after uIR and mice were sacrificed 1 day later, at 2 or 7 or 14 days. Blood was collected to measure serum creatinine as an indication of left kidney function (C). (The purpose of detecting uIR 2d is to show that AKI has formed on day 2, so adding medicine on day 3 belongs to the treatment of AKI rather than the prevention or intervention of AKI formation. Both uIR 7d and uIR 14d represent CKD)

[0042] see test results figure 1 : Unilateral renal ischemia reperfusion (uIR) simulates the progression of kidney from acute kidney injury to chronic kidney disease in the human body.

[0043] (A) Ischemic side kidney weight / body weight (mg / g): When unilateral ischemia...

Embodiment 2

[0054] C57BL / 6 mice (male, 8-10 weeks old) were subjected to 30 min of unilateral ischemia of the left kidney followed by reperfusion. From the third day of unilateral renal ischemia reperfusion (uIR), intraperitoneal injection of TUDCA 250 mg / kg / day or the same amount of normal saline (NS) was given. Right nephrectomy was performed on day 13 after uIR, and mice were sacrificed 1 day later (ie, on day 14) and blood was collected to measure serum creatinine as an indication of left kidney function.

[0055] see test results figure 2 : In vivo experiments demonstrated that TUDCA improved renal dysfunction after ischemic acute kidney injury.

[0056] Serum creatinine (mg / dL): Compared with the control group (sham+NS), the concentration of serum creatinine in the operation group was significantly higher than that in the control group, ***P<0.001, indicating that uIR caused impaired renal function. At 14 days of uIR, compared with the NS injection group, the concentration of ser...

Embodiment 3

[0062] C57BL / 6 mice (male, 8-10 weeks old) were subjected to 30 min of unilateral ischemia of the left kidney followed by reperfusion. From the third day of uIR, intraperitoneal injection of TUDCA250mg / kg / day or the same amount of NS was given. Kidney tissue was collected on day 14.

[0063] see test results image 3 : In vivo experiments demonstrated that TUDCA improved tubular atrophy and compensatory hypertrophy of the contralateral kidney after acute kidney injury.

[0064] (A) HE staining of paraffin sections of renal tissue: Compared with the control group, at 14 days of uIR, some renal tubules fell off, the remaining renal tubules were structurally disordered, most of the renal tubules atrophied, and the renal tubules and interstitial space were obviously expanded Accompanied by a large number of necrotic fragments in the small lumen. When uIR was 14 days, there was a significant reduction in atrophic ducts in the TUDCA-injected group compared with the NS-injected gr...

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Abstract

The invention discloses application of Tauroursodeoxycholic acid (TUDCA) in preparing medicine for treating conversion from acute kidney injuries to chronic kidney diseases. Due to TUDCA treatment, some kidney functions injured by acute kidney injuries are recovered; tubular atrophy caused after acute kidney injuries, contralateral kidney compensatory hypertrophy, renal interstitial fibrosis, kidney chronic inflammation and tubular cell death are improved. Then, the conversion process from the acute kidney injury (AKI) to the chronic kidney disease (CKD) is delayed, and the medicine can be used for preventing the conversion from AKI to CKD.

Description

technical field [0001] The invention belongs to the application field of compounds, and in particular relates to a new application of tauroursodeoxycholic acid. Background technique [0002] Acute kidney injury (AKI) is a common kidney disease characterized by rapid decline or even loss of kidney function. The pathological feature of AKI is damage and death of renal tubular epithelial cells. Following injury, surviving tubular cells undergo dedifferentiation, proliferate to replace damaged tubular epithelial cells and restore tubular integrity. [0003] In the past AKI was considered a completely reversible disease. However, a large number of recent epidemiological and animal experiments have shown that in the case of severe AKI, renal tubular epithelial repair is incomplete or maladaptive repair occurs, making AKI turn into CKD (chronic kidney disease, CKD). Therefore, AKI is an important risk factor for the occurrence and development of chronic kidney disease. [0004]...

Claims

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Application Information

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IPC IPC(8): A61K31/575A61P13/12
CPCA61K31/575A61P13/12
Inventor 董政舒绍群唐程远
Owner THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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