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1. WO2021089053 - NANO COMPLEX FOR TARGETED REPAIRING OF NEUROVASCULAR LESION, AND PREPARATION AND USE THEREOF

Publication Number WO/2021/089053
Publication Date 14.05.2021
International Application No. PCT/CN2020/127588
International Filing Date 09.11.2020
IPC
A61K 9/127 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
9Medicinal preparations characterised by special physical form
10Dispersions; Emulsions
127Liposomes
A61K 47/42 2017.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
A61K 31/7105 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7088Compounds having three or more nucleosides or nucleotides
7105Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61P 3/10 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
3Drugs for disorders of the metabolism
08for glucose homeostasis
10for hyperglycaemia, e.g. antidiabetics
A61P 25/28 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25Drugs for disorders of the nervous system
28for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25Drugs for disorders of the nervous system
Applicants
  • 上海交通大学医学院 SHANGHAI JIAOTONG UNIVERSITY SCHOOL OF MEDICINE [CN]/[CN]
Inventors
  • 高小玲 GAO, Xiaoling
  • 宋清香 SONG, Qingxiang
  • 章倩 ZHANG, Qian
  • 陈红专 CHEN, Hongzhuan
  • 江淦 JIANG, Gan
Agents
  • 上海盈盛知识产权代理事务所(普通合伙) SHANGHAI WINSUN INTELLECTUAL PROPERTY AGENCY
Priority Data
201911075877.606.11.2019CN
Publication Language Chinese (ZH)
Filing Language Chinese (ZH)
Designated States
Title
(EN) NANO COMPLEX FOR TARGETED REPAIRING OF NEUROVASCULAR LESION, AND PREPARATION AND USE THEREOF
(FR) NANOCOMPLEXE DESTINÉ À LA RÉPARATION CIBLÉE D'UNE LÉSION NEUROVASCULAIRE, SA PRÉPARATION ET SON UTILISATION
(ZH) 一种靶向修复神经血管病变的纳米复合物及其制备与应用
Abstract
(EN)
Disclosed is a nano complex for the targeted repairing of a neurovascular lesion. The nano complex comprises a lipid, an apolipoprotein and a targeted peptide, and the targeted peptide is formed by covalently linking, by means of a bridge structure, a nanocarrier linking end and a peptide chain which targets RAGE, which specifically binds to cerebrovascular lesion site. On the basis of AD and the high expression of RAGE in cerebrovascular and brain parenchyma in diabetic encephalopathy, the nano complex, which has been modified by the targeted peptide, is capable of mainly binding, in a targeted manner, to the cerebrovascular endothelium by means of linking the targeted peptide, so as to repair vascular endothelial cells, promote the removal of Aβ plaque near blood vessels, and repair cerebrovascular and neurovascular unit components such as microglial cells, astrocytes and neurons. The aim of ameliorating cognitive impairment is achieved by the combined repairing of multiple components and then restoring cerebrovascular functions and cerebral blood flow. The nano complex itself has a disease repair effect and can also carry drugs, thereby achieving the delivery of drugs to cerebrovascular lesion site.
(FR)
Est divulgué, un nanocomplexe destiné à la réparation ciblée d'une lésion neurovasculaire. Le nanocomplexe comprend un lipide, une apolipoprotéine et un peptide ciblé, et le peptide ciblé est formé par liaison covalente, au moyen d'une structure de pont, d'une extrémité de liaison de nanosupport et d'une chaîne peptidique qui cible RAGE, qui se lie plus particulièrement à un site de lésion cérébrovasculaire. Sur la base de l'AD et de l'expression élevée de RAGE dans le parenchyme cérébral et cérébrovasculaire dans l'encéphalopathie diabétique, le nanocomplexe, qui a été modifié par le peptide ciblé, est apte à se lier principalement, de manière ciblée, à l'endothélium cérébrovasculaire au moyen de la liaison du peptide ciblé, de manière à réparer des cellules endothéliales vasculaires, à favoriser l'élimination de la plaque d'Aβ à proximité des vaisseaux sanguins, et à réparer des composants d'unités cérébrovasculaires et neurovasculaires tels que les cellules microgliales, les astrocytes et les neurones. L'objectif de l'amélioration de la déficience cognitive est obtenu par la réparation combinée de composants multiples puis par la restauration des fonctions cérébrovasculaires et du flux sanguin cérébral. Le nanocomplexe lui-même a un effet de réparation de maladie et peut également transporter des médicaments, ce qui permet d'obtenir l'administration de médicaments à un site de lésion cérébrovasculaire.
(ZH)
一种靶向修复神经血管病变的纳米复合物,所述纳米复合物包括脂质、载脂蛋白和靶向肽,所述靶向肽由桥联结构将链接纳米载体端和靶向特异结合脑血管病变部位RAGE的肽链共价连接形成。靶向肽修饰的纳米复合物基于AD和糖尿病脑病中脑血管和脑实质中RAGE高表达,通过连接靶向肽,能够主要靶向结合在脑血管内皮上,修复血管内皮细胞,促进血管旁Aβ斑块的清除,修复脑血管及神经血管单元组分如小胶质细胞、星形胶质细胞和神经元,通过多组分的联合修复进而修复脑血管的功能和脑血流,达到认知障碍改善的目的。此纳米复合物本身具有疾病修复作用的同时还可载带药物,实现药物的脑血管病变部位递送。
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