Utilization of cilastatin in inhibiting renal disorder

A technology for cilastatin and renal injury, which is applied in the application field of cilastatin in inhibiting renal injury to achieve the effect of avoiding renal injury

Pending Publication Date: 2020-12-04
NIIGATA UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] At present, the method recommended as a preventive method for contrast medium-induced renal injury is intravenous administration of osmotic infusion preparations such as physiological saline and sodium bicarbonate infusion before and after contrast examination (Non-Patent Document 1), but this is not the case. Demonstrated efficacy with a high level of evidence

Method used

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  • Utilization of cilastatin in inhibiting renal disorder
  • Utilization of cilastatin in inhibiting renal disorder
  • Utilization of cilastatin in inhibiting renal disorder

Examples

Experimental program
Comparison scheme
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Embodiment

[0129] Hereinafter, although this invention is demonstrated based on an Example, this invention is not limited to these Examples.

[0130] Among the iodine-based contrast agents used, iomeprol is the Japanese Pharmacopoeia iomeprol injection (“Iomeron (registered trademark) 350” (Bracco-Bracco-Eisai Co., Ltd.)), and iohexol is the Japanese Pharmacopoeia iodine Hexylene injection (“Omnipaque (registered trademark) 350” (Daiichi Sankyo Co., Ltd.)), and iopamiron (registered trademark) 370” (Bayer Yakuhin, Ltd.) ), iodixanol is iodixanol injection "Visipaque (registered trademark) 320" (Daiichi Sankyo Co., Ltd.), ioversol is ioversol injection "Optiray (registered trademark) 350" (Fuji Pharmaceutical Industry Co., Ltd.), iopromide is iopromide injection ("Iopromide 370 injection "FRI"" (FUJIFILMRI Pharma Co., Ltd. / Input source: Bayer Yakuhin, Ltd.)). In addition, the cilastatin used was cilastatin sodium (Sigma-Aldrich Japan K.K.).

[0131] The animal species used was C57BL / 6J ...

reference example 1

[0133] A mouse model of contrast-induced nephropathy was established.

[0134] method

[0135] The left kidneys of C57BL / 6J mice (male, 9-12 weeks old, Charles River Laboratories International) were removed, and the right renal stem was ligated for 30 minutes 14 days later. Then perform reperfusion. In the iomeprol administration group, 200 μL of iomeprol was intravenously administered 24 hours after the start of reperfusion. In the control group, 200 μL of physiological saline was administered from the tail vein instead of iomeprol. Animals from each group were dissected and evaluated 48 hours after administration.

[0136] Urine was stored in metabolic cages 24 hours before dissection, and the right kidney was removed after blood was collected from the inferior vena cava during dissection. The collected blood was centrifuged at room temperature at 800 g for 30 minutes to separate and recover serum. The resulting urine / serum was stored at -80°C until analysis.

[0137...

reference example 2

[0143] Using kidney-specific complete megalin knockout mouse NDRG1-Cre and its control mice (non-induced), it was verified that the contrast agent (iodine) in Uptake in proximal tubule epithelial cells depends on megalinity.

[0144] EPMA is one of electron microprobe (EMP) devices that analyze constituent elements based on the wavelength and intensity of characteristic X-rays unique to each element generated by irradiating an object with electron beams. Iodine contained in (Norby et al., Scanning Microsc, 1990, Vol. 4, pp. 651-666). It is known that the contrast agent is not metabolized in the living body, and the behavior of the contrast agent itself can be verified by analyzing the distribution of iodine.

[0145] The "thin film quantification method" can be used for the analysis of biological samples such as kidney tissue sections. In EPMA analysis, the following relationship holds true when electron beam irradiation and X-ray detection are performed under the same condi...

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Abstract

One of the problems to be solved by the present invention is to provide an inhibitor of renal disorder induced by an iodine contrast medium. In the present invention, use is made of cilastatin or a pharmaceutically acceptable salt thereof.

Description

technical field [0001] The invention relates to the application of cilastatin in inhibiting kidney injury. Specifically, it relates to an inhibitor of renal injury induced by an iodine-based contrast medium, comprising cilastatin or a pharmaceutically acceptable salt thereof. Background technique [0002] (contrast agent) [0003] X-ray contrast technology is of great significance in clinical scenarios such as grasping disease symptoms and formulating diagnosis and treatment policies. X-ray attenuation in soft tissues other than bones is small, so it is difficult to delineate tissues. It is known that the attenuation of X-rays is proportional to the density of a substance and proportional to the third power of the atomic number of constituent elements, and iodine compounds have attracted attention in the development of contrast agents for blood vessels. A contrast agent containing such an iodine compound as an active ingredient is called an iodine-based contrast agent. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61P13/12A61K49/04
CPCA61P13/12A61K31/198A61K49/04A61K9/0019
Inventor 斋藤亮彦后藤佐和子平山吉朗关根盛
Owner NIIGATA UNIVERSITY
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