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Application of PRMT5 inhibitor in preparation of hearing protection drugs

A technology of inhibitors and drug effects, applied in the field of hearing protection drugs, PRMT5 inhibitors, can solve the problems of limited clinical effects such as the number and quality of residual hair cells and spiral neurons, achieve good industrialization prospects, and reduce hearing protection effect, no side effects

Active Publication Date: 2021-12-31
EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no preventive or therapeutic drug for hearing loss clinically. The commonly used treatment methods include hearing aids and cochlear implants, although they can improve the patient's hearing, but none of them can restore the autonomous hearing function in the true sense, and their clinical effects are limited. Quantity and quality of residual hair cells and spiral neurons

Method used

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  • Application of PRMT5 inhibitor in preparation of hearing protection drugs
  • Application of PRMT5 inhibitor in preparation of hearing protection drugs
  • Application of PRMT5 inhibitor in preparation of hearing protection drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Example 1PRMT5 detecting the expression level in mouse inner ear

[0090] 1.1 subjects and grouping

[0091] Use two days after birth wild type C57BL / 6 mice were anesthetized for inner ear cochlear removed and cultured in vitro, were randomly divided into 3 groups:

[0092] Control group (Con) (intact): No addition of the drug, the culture was co-cultured for 24 hours in serum-free DMEM / F12;

[0093] Injury group cisplatin (Cis): use of serum-free DMEM containing 30μM cisplatin / F12 medium for 24 hours;

[0094] PRMT5 inhibitor + cisplatin group (LLY-283-Cis): in advance using serum-free DMEM containing potent selective inhibitors of formula PRMT5 LLY-283 (200μM) I shown in / F12 medium with mice basilar membrane in vitro co-culture for 2 hours and then serum-free DMEM containing 30μM cisplatin and the 200μM LLY-283 / F12 medium for 24 hours co-treatment.

[0095] 1.2PRMT5 detecting the expression level in mouse inner ear

[0096] Separated by SDS-PAGE electrophoresis ...

Embodiment 2

[0098] Test Example 2 In vitro inhibitors have demonstrated protective effect PRMT5 damage cochlear hair cells in mice

[0099] 2.1 subjects and grouping

[0100] Use two days after birth wild type C57BL / 6 mice were anesthetized for inner ear cochlear removed and cultured in vitro, were randomly divided into 3 groups:

[0101] Control group (Con) (intact): No addition of the drug, the culture was co-cultured for 24 hours in serum-free DMEM / F12;

[0102] Injury group cisplatin (Cis): use of serum-free DMEM containing 30μM cisplatin / F12 medium for 24 hours;

[0103] 200μM PRMT5 inhibitor group (LLY-283 200μM): use of serum-free DMEM containing 200μM LLY-283's / F12 medium for 24 hours.

[0104] 100 M + cisplatin group PRMT5 inhibitors (LLY-283100μM-Cis): use of serum-free DMEM containing previously PRMT5 selective potent inhibitors LLY-283 (100μM) is / F12 medium basement membrane in vitro co-culture of mouse cochlea 2 h, and then serum-free DMEM containing 30μM cisplatin and ...

Embodiment 3

[0115] Example 3.PRMT5 inhibitor can effectively reduce the spiral ganglion neuronal damage caused by cisplatin

[0116] 3.1 subjects and grouping

[0117] Use two days after birth wild type C57BL / 6 mice were randomly divided into four groups:

[0118] Control group (Con or Control): No addition of the drug, the culture was co-cultured for 24 hours in serum-free DMEM / F12;

[0119] Injury group cisplatin (Cis): using 30μM cisplatin for 24 hours;

[0120] PRMT5 inhibitors low dose group (LLY-283 100μM-Cis): 100 M PRMT5 advance using a selective potent inhibitors LLY-283 mouse cochlear basement membrane in vitro co-culture for 2 hours and then administered with 30μM cisplatin 100μMLLY-283 total 24 hours.

[0121] PRMT5 inhibitor high dose group (LLY-283 200μM-Cis): 200 M PRMT5 advance using a selective potent inhibitors LLY-283 mouse cochlear basement membrane in vitro co-culture for 2 hours and then administered with 30μM cisplatin 200μMLLY-283 total 24 hours.

[0122] 3.2PRMT5 ...

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Abstract

The invention belongs to the field of biological medicine, discloses application of PRMT5 as a drug target in hearing protection, and particularly discloses application of a PRMT5 inhibitor in preparation of drugs for preventing and / or treating hearing injury. As a hearing protection component, the PRMT5 inhibitor can effectively prevent hearing injury or effectively treat hearing injury. The invention also discloses a drug or kit containing the PRMT5 inhibitor for hearing protection. The invention provides a new idea for prevention and treatment of hearing injury, thereby having a broad clinical application prospect.

Description

Technical field [0001] The present invention is in the biomedical field, particularly relates to the use of hearing protection PRMT5 inhibitor in the manufacture of a medicament for. Background technique [0002] Deafness is one of the most common human sensory disorders, serious impact at all stages of life deafness with daily communication and work in patients with moderate to severe hearing loss patients even lost their jobs, withdrawn, infants, children and adolescents deafness affect language development and learning, the patient's family and community also caused a great burden. [0003] Hearing loss due to inner ear hair cells (HCs) or spiral ganglion neurons (SGNs) death called sensorineural hearing loss is the most common type of deafness. There are many, including ototoxic drugs, noise, hereditary, age, metabolic, cancer and autoimmune diseases and other known causes of sensorineural hearing loss. In recent years, a large number of widely used chemotherapy drugs and ant...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/519A61P27/16
CPCA61K45/00A61K31/519A61P27/16
Inventor 何英姿唐冬梅郑智伟刘畅
Owner EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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