COMPOSITION FOR PREVENTING OR TREATING PERIPHERAL NEUROPATHY, CONTAINING ISOQUINOLINE DERIVATIVE AS ACTIVE INGREDIENT

• Main Authors: LEE, Ji Hyun, CHOI, Se Myeong, IM, Sangwoo, YUN, Jeanho, CHO, Jong Hyun
• Format: Patent
• Language: English; French; Korean
• Published: 18.04.2024
• Subjects: FOODS OR FOODSTUFFS; FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BYSUBCLASSES A23B - A23J; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OFNUTRITIVE QUALITIES, PHYSICAL TREATMENT; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES

The present invention relates to a pharmaceutical composition for preventing or treating peripheral neuropathy, and the like. The present invention has been completed by confirming that an isoquinoline derivative discovered through a screening based on mitophage activity exhibits an excellent mitophage promoting effect, and thus, the isoquinoline derivative can be utilized as a fundamental therapeutic agent for peripheral neuropathy. Specifically, it has been found that the isoquinoline derivative according to the present invention treats hyperalgesia in an animal model of anticancer drug-inducible peripheral neuropathy, also suppresses morphological changes of sensory nerves, which have been identified as a key cause of peripheral neuropathy, and can increase the distribution and number of peripheral nerves. Therefore, the isoquinoline derivative according to the present invention is a fundamental therapeutic agent capable of suppressing the main symptoms and causes of peripheral neuropathy, particularly, anticancer drug-induced peripheral neuropathy, and is expected to be usefully utilized in the field of prevention, amelioration, and/or treatment of the disease. La présente invention concerne une composition pharmaceutique destinée à prévenir ou traiter une neuropathie périphérique, et similaire. La présente invention a été rendue possible par la confirmation qu'un dérivé d'isoquinoléine, découvert par un criblage basé sur l'activité de mitophagie, présentait un excellent effet favorisant la mitophagie et, ainsi, le dérivé d'isoquinoléine pouvait être utilisé en tant qu'agent thérapeutique fondamental pour la neuropathie périphérique. Plus précisément, il a été découvert que le dérivé d'isoquinoléine selon la présente invention traitait l'hyperalgésie dans un modèle animal de neuropathie périphérique induite par un médicament anticancéreux, supprimait également des changements morphologiques de nerfs sensoriels, qui ont été identifiés en tant que cause majeure de neuropathie périphérique, et pouvait augmenter la distribution et le nombre de nerfs périphériques. Par conséquent, le dérivé d'isoquinoléine selon la présente invention est un agent thérapeutique fondamental capable de supprimer les symptômes principaux et les causes d'une neuropathie périphérique, en particulier, d'une neuropathie périphérique induite par un médicament anticancéreux, et devrait être utilement utilisé dans le domaine de la prévention, de l'amélioration et/ou du traitement de cette maladie. 본 발명은 말초신경병증의 예방 또는 치료용 약학적 조성물 등에 관한 것으로서, 미토파지 활성에 기반한 스크리닝을 통해 발굴된 이소퀴놀린 유도체가 우수한 미토파지 촉진 효과를 발휘하며, 이를 통해 말초신경병증의 근본적인 치료제로 활용될 수 있음을 확인하여 완성된 것이다. 구체적으로, 본 발명에 따른 이소퀴놀린 유도체는 항암제 유도성 말초신경병증 동물모델에서 통각과민증상을 치료할 뿐만 아니라, 말초신경병증의 핵심 병인으로 밝혀진 감각신경의 형태적 변화를 억제하고, 말초신경의 분포 및 수를 증가시킬 수 있음이 확인되었다. 따라서, 본 발명에 따른 이소퀴놀린 유도체는 말초신경병증, 특히, 항암제 유도성 말초신경병증의 주요 증상 및 병인을 억제할 수 있는 근본적인 치료제로서 상기 질병의 예방, 개선, 및/또는 치료 분야에서 유용하게 활용될 것으로 기대된다.