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Application of magnesium isoglycyrrhizinate to preparation of medicine for lowering ototoxicity caused by aminoglycoside antibiotics

A technology of aminoglycosides and magnesium isoglycyrrhizinate, applied in the field of application of magnesium isoglycyrrhizinate in the preparation of drugs for reducing ototoxicity caused by aminoglycoside antibiotics

Inactive Publication Date: 2018-07-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the side effects restricting the widespread use of this type of drug are serious nephrotoxicity and irreversible ototoxicity.
There is no report that magnesium isoglycyrrhizinate can effectively reduce ototoxicity caused by aminoglycoside antibiotics

Method used

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  • Application of magnesium isoglycyrrhizinate to preparation of medicine for lowering ototoxicity caused by aminoglycoside antibiotics
  • Application of magnesium isoglycyrrhizinate to preparation of medicine for lowering ototoxicity caused by aminoglycoside antibiotics
  • Application of magnesium isoglycyrrhizinate to preparation of medicine for lowering ototoxicity caused by aminoglycoside antibiotics

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0008] Embodiment 1: ABR hearing test after multiple administrations in SD rats

[0009] The main steps are as follows:

[0010] Thirty male SD rats were randomly divided into 5 groups according to body weight, 6 in each group.

[0011] The experimental design and grouping of the protective effect of magnesium isoglycyrrhizinate on the ototoxicity induced by aminoglycoside antibiotics gentamicin and amikacin are as follows: Control group (administration of normal saline, i.p), GM group (70mg / kg / day, i.p), GM +MgIG group (half an hour after MgIG50mg / kg / day administration, then GM 70mg / kg / day, all i.p), AMK group (210mg / kg / day, i.p), AMK+MgIG group (MgIG 50mg / kg / day After half an hour of administration, give AMK 210mg / kg / day, both i.p). The administration period is 3 weeks.

[0012] The ABR test was carried out once a week, and the process was as follows: Weigh the rats, inject 10% chloral hydrate intraperitoneally according to the mass-to-volume ratio of 0.3ml / kg; Insert t...

Embodiment 2

[0015] Example 2: Effects of combined use of magnesium isoglycyrrhizinate on the accumulation of AGs in the inner ear of SD rats

[0016] The main steps are as follows:

[0017] The establishment method and dosage regimen of the ototoxicity model caused by aminoglycoside drugs are the same as in Example 1. 4 hours after the administration on the last day, the rats were sacrificed by exsanguination from the abdominal aorta, and the inner ear tissues were collected to measure the accumulation of gentamicin and amikacin in the inner ear of SD rats.

[0018] Experimental results:

[0019] LC-MS / MS was used to detect the distribution of gentamicin and amikacin in the inner ear tissue of SD rats after multiple administrations of gentamicin and amikacin alone or in combination with magnesium isoglycyrrhizinate. The result is as figure 2 As shown, the combination of magnesium isoglycyrrhizinate can significantly reduce the distribution of gentamicin and amikacin in the inner ear t...

Embodiment 3

[0020] Example 3: Expression of mRNA levels of mitochondrial bioremediation regulatory factors in inner ear tissues of SD rats after multiple administrations

[0021] The main steps are as follows:

[0022] The establishment method and dosage regimen of the ototoxicity model caused by aminoglycoside drugs are the same as in Example 1. The rats were sacrificed 4 hours after administration on the last day, and inner ear tissues were taken. RNA was extracted and quantified according to the Takara Total RNA Extraction Kit. According to the instructions of the RT-PCR kit, the mRNA was reverse transcribed into cDNA. Real-time fluorescent quantitative PCR analysis was performed according to the instruction manual of Thermal Cycler DiceTM Real TimeSystem (TakaRa Code: TP800). Detection of mRNA expression of mitochondrial biorepair regulators in inner ear tissue: peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory transcription factor 1 (NRF...

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Abstract

The invention discloses application of magnesium isoglycyrrhizinate (MgIG) to the preparation of a medicine for lowering the ototoxicity caused by aminoglycoside antibiotics, and relates to the fieldof natural medicines. A rat ototoxicity model caused by an aminoglycoside antibiotic gentamicin (GM) and amikacin (AMK) is established; discovering that by jointly using the MgIG, the MgIG can be usedfor effectively ameliorating the threshold value increment of the auditory brainstem response (ABR) caused by the aminoglycoside antibiotisc, and meanwhile, is used for lowering the concentration ofan aminoglycoside medicine in the tissue of an inner ear of a rat and reversing the dysfunction, which is caused by the medicine, of a mitochondrion in the tissue of the inner ear, and the MgIG in theapplication provided by the invention can be used cooperatively to antagonize the ototoxicity caused by the aminoglycoside antibiotics.

Description

technical field [0001] The invention belongs to the field of natural medicines and relates to a new application of magnesium isoglycyrrhizinate, that is, the application of magnesium isoglycyrrhizinate in the preparation of drugs for reducing ototoxicity caused by aminoglycoside antibiotics. Background technique [0002] Infectious diseases have always been one of the diseases that pose a great threat to human health. Epidemiological statistics show that infectious diseases cause tens of millions of deaths every year, accounting for one-third of the global annual death toll; the global market sales of anti-infective drugs are nearly 100 billion U.S. dollars, accounting for about 10%, and an annual growth rate of not less than 8%; while my country is the country with the largest sales of anti-infective drugs in the world, and this demand will further increase with the increase in the number of drug users. However, due to the abuse of anti-infective drugs and the lack of new a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61P27/16
CPCA61K31/704
Inventor 王广基周芳姚澜
Owner CHINA PHARM UNIV
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