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Application of 18 beta-glycyrrhetinic acid (or salt) for serving as auxiliary treating drug capable of easing acute kidney injury caused by chemotherapeutic drug, namely cis-platinum

A technology for acute kidney injury and glycyrrhetinate, which is applied in the field of pharmacotherapeutics and can solve problems such as limiting clinical application

Inactive Publication Date: 2017-03-29
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical observation found that the incidence of renal damage in hospitalized patients treated with cisplatin reached 25% to 35%, and the acute kidney injury caused by it severely limited its clinical application.

Method used

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  • Application of 18 beta-glycyrrhetinic acid (or salt) for serving as auxiliary treating drug capable of easing acute kidney injury caused by chemotherapeutic drug, namely cis-platinum
  • Application of 18 beta-glycyrrhetinic acid (or salt) for serving as auxiliary treating drug capable of easing acute kidney injury caused by chemotherapeutic drug, namely cis-platinum
  • Application of 18 beta-glycyrrhetinic acid (or salt) for serving as auxiliary treating drug capable of easing acute kidney injury caused by chemotherapeutic drug, namely cis-platinum

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Effects of 18β-GA on general conditions and kidneys of CP-induced acute kidney injury (AKI) mice The main steps are as follows:

[0026] 60 male C57BL / 6J mice, weighing 18±2 grams, were randomly divided into the following 6 groups (n=10): control group (Vehicle), control+18β-GA (100mg / kg) group, CP group, CP+ 18β-GA (25mg / kg) group, CP+18β-GA (50mg / kg) group and CP+18β-GA (100mg / kg) group. On the first day, the control group and the control +18β-GA (100mg / kg) group were intraperitoneally injected with 0.9% sodium chloride 0.5ml, the CP group, the CP+18β-GA (25mg / kg) group, the CP+18β-GA (50mg / kg) group and CP+18β-GA (100mg / kg) group were intraperitoneally injected with CP (20mg / kg), while CP+18β-GA (25mg / kg) group, CP+18β-GA (50mg / kg) Group and CP+18β-GA (100mg / kg) were administered by intragastric administration for 3 consecutive days, and on the fourth day, 10% chloral hydrate was injected intraperitoneally, and the animals were sacrificed after anesthesi...

Embodiment 2

[0029] Example 2: Effect of 18β-GA on CP-induced renal pathology in mice

[0030] Main operation steps: the kidney tissues of different groups of mice were fixed in formalin solution for 24h to 48h, the samples were dehydrated with alcohol and transparent with xylene, and then embedded in paraffin. The embedded tissue blocks are hardened and sliced ​​with a microtome. Before staining, remove the paraffin in the paraffin section in xylene, dehydrate with ethanol from high concentration to low concentration, and finally rinse with water (distilled water) to start staining. Stain in the hematoxylin staining solution for 5 minutes to 15 minutes, and wash off the excess staining solution with running water. Act in 1% hydrochloric acid ethanol for 1-3 seconds, wash with water, add blue solution (0.5% light ammonia water) to turn blue for 10-30 seconds, and then stain with 0.5% eosin dye solution for about 1-3 minutes. After washing with distilled water for a while, dehydration was...

Embodiment 3

[0032] Embodiment 3: The effect of 18β-GA on CP-induced mouse serum Cr and BUN

[0033] Main steps: take different groups of mouse serum as samples, according to the creatinine Cr test box (inosinate oxidase method, microwell 96T microplate method) and urea nitrogen BUN test box (urea enzyme method) (Nanjing Jiancheng Bioengineering Co., Ltd. Institute) instructions for operation.

[0034] Detecting serum Cr and BUN found that compared with CP-induced AKI mice, 18β-GA (50, 100mg / kg) could significantly reduce serum Cr and BUN levels (p image 3 A, image 3 B). The above experiments suggest that 18β-GA has a protective effect on CP-induced AKI.

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Abstract

The invention belongs to the field of pharmacotherapeutics, and particularly relates to application of 18 beta-glycyrrhetinic acid (or salt) for serving as an auxiliary treating drug capable of easing acute kidney injury caused by a chemotherapeutic drug, namely cis-platinum, wherein the 18 beta-glycyrrhetinic acid (or salt) is one of the main components of liquorice. The cis-platinum serves as a commonly-used chemotherapy drug, and clinical application thereof is restricted by kidney toxicity thereof. The levels of creatinine and urea nitrogen in the acute kidney injury induced by the cis-platinum can be inhibited by the18 beta-glycyrrhetinic acid, expression of KIM-1 injured protein is lowered, and apoptosis of renal tubular epithelial cells caused by the cis-platinum is inhibited. According to the application of the 18 beta-glycyrrhetinic acid (or salt) for serving as the auxiliary treating drug capable of easing the acute kidney injury caused by the chemotherapeutic drug, namely the cis-platinum, the effect that the 18 beta-glycyrrhetinic acid has a protecting effect on the acute kidney injury caused by the cis-platinum is discovered for the first time, a mechanism of the 18 beta-glycyrrhetinic acid is related to inhibiting of apoptosis of the renal tubular epithelial cells, and a novel potential drug is provided for Chinese medicine anti-cancer adjuvant therapy.

Description

technical field [0001] The invention belongs to the field of pharmacotherapeutics, and discloses the application of 18β-glycyrrhetinic acid (or salt) as an adjuvant treatment drug for alleviating acute kidney injury caused by chemotherapy drug cisplatin. Background technique [0002] The nephrotoxicity of clinical chemotherapy drugs has always been the bottleneck of tumor treatment. How to reduce the toxic and side effects of chemotherapy drugs is one of the focuses of research in the process of tumor treatment. Cisplatin (cis-dichlorodiammino platinum Ⅱ or Cisplatin, CP), as a widely used cytotoxic chemotherapy drug, has a good effect on a variety of tumors. The activity of cisplatin is related to the concentration of chloride ions. In the low-chloride environment of the intracellular fluid, the chloride ions in the cisplatin structure undergo hydration dissociation and are replaced by water to generate positively charged hydration complex ions, which undergo addition react...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P13/12
CPCA61K31/56
Inventor 马陶陶李俊黄成孟晓明李增
Owner ANHUI MEDICAL UNIV
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