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Application of mTOR signal path inhibitor to preparation of medicament for preventing or treating extragenetic hearing impairment

A technology for signaling pathways and hearing impairment, which is applied in the field of mTOR signaling pathway inhibitors and the preparation of drugs for the prevention or treatment of non-genetic hearing impairment. problems, to achieve the effect of preventing and treating non-hereditary hearing impairment and improving hearing level

Inactive Publication Date: 2018-07-24
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the molecular mechanism of non-genetic hearing impairment is still unclear. There is evidence that it is related to the abnormal activity of calcium-dependent protease, inner ear microcirculation disturbance, inner ear cell free radical damage and cell apoptosis. Currently, there is no effective clinical treatment. A means to prevent and treat hearing impairment caused by non-genetic factors
Potential prevention and treatment methods include the use of glucocorticoids, antioxidants, neurotrophic factors combined with vasodilators, hyperbaric oxygen, acupuncture therapy, surgical treatment, and cochlear implantation, but there are large differences in the treatment effect and the effect is not obvious And other issues

Method used

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  • Application of mTOR signal path inhibitor to preparation of medicament for preventing or treating extragenetic hearing impairment
  • Application of mTOR signal path inhibitor to preparation of medicament for preventing or treating extragenetic hearing impairment
  • Application of mTOR signal path inhibitor to preparation of medicament for preventing or treating extragenetic hearing impairment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] This example takes rapamycin as an example to study the protective effect of mTOR signaling pathway inhibitors on cochlear spiral ganglion cells.

[0041] 1. Gentamicin causes loss of cochlear spiral ganglion cells in vivo

[0042] Twenty-eight healthy C57B6 / J mice were purchased from the Experimental Animal Center of Southern Medical University, 7-9 weeks old, regardless of sex, and randomly divided into two groups, the control group and the model group. Mice were kept in a quiet, warm animal breeding room, given sufficient food and water. Mice were cared for according to Animal Care and Use Committee guidelines. The mice in the control group were intraperitoneally injected with 5ml / kg normal saline for 15 consecutive days. The mice in the model group were injected with 40 mg / kg furosemide intraperitoneally for 15 consecutive days, and then 200 mg / kg gentamicin sulfate was injected intraperitoneally 20 minutes later. Auditory brainstem response test (ABR) test was c...

Embodiment 2

[0053] This example takes rapamycin as an example to study the protective effect of mTOR signaling pathway inhibitors on cochlear hair cells.

[0054] 1. Gentamicin can induce the loss of cochlear hair cells cultured in vitro

[0055] Twenty C57B6 / J suckling mice born 2-3 days old from healthy C57B6 / J pregnant mice were purchased from the Experimental Animal Center of Southern Medical University. . After 12 hours, the tissues with good adherent growth and clearly visible cell outlines were selected for further experiments. The available tissues were randomly divided into control group and gentamicin group according to the site. The control group was the same amount of complete culture solution as the experimental group, and the gentamicin group was the complete culture solution containing 50 μM gentamicin. The culture was terminated after 48 hours, fixed with 4% paraformaldehyde, stained with Phalloidin (1:200) in the dark for 30 minutes, rinsed with PBS, mounted, observed ...

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Abstract

The invention discloses application of a mTOR signal path inhibitor to preparation of a medicament for preventing or treating extragenetic hearing impairment. The mTOR signal path inhibitor is selected from at least one of sirolimus, sirolimus analogue and second-generation mTOR signal path inhibitor; the sirolimus analogue is selected from at least one of everolimus, temsirolimus and Deforolimus;the second-generation mTOR signal path inhibitor is selected from at least one of PI3K / mTOR double inhibitor, selective mTORC1 / 2 inhibitor and ATP competitive mTOR kinase inhibitor. As found by the inventor of the application, the mTOR signal path inhibitor can effectively relieve damage to inner ear hair cells and spiral ganglion cells caused by non-genetic factors such as ototoxic drug, remarkably improve the impaired listening ability, and effectively prevent and treat extragenetic hearing impairment.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the use of mTOR signaling pathway inhibitors in the preparation of drugs for preventing or treating non-hereditary hearing impairment. Background technique [0002] According to the second national survey on the population of persons with disabilities, there are 27.8 million people with hearing and speech disabilities, surpassing physical disabilities and visual disabilities as the number one cause of disability. Sensorineural hearing impairment accounts for more than 70% of the hearing-impaired population, and conductive hearing impairment accounts for about 30%. Conductive hearing impairment can be improved by surgically repairing or reconstructing the sound transmission system or wearing hearing aids; while sensorineural hearing impairment is mainly due to hair cell lesions and / or spiral neuron damage, and mammalian cochlear hair cells and spiral nerves Damaged...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/436A61P27/16
CPCA61K31/436A61K45/00
Inventor 唐杰李翠限郭莎莎
Owner SOUTHERN MEDICAL UNIVERSITY
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