Zhejiang University

Fuqiang Hu

Hong Yuan

Kai Wang

Lijuan Wen

Tingting Meng

Yongzhong Du

Pan Meng

The present invention relates to a use of Axitinib and analogs thereof in the preparation of a blood-brain barrier permeability regulator. The blood-brain barrier permeability regulator can reduce blood-brain barrier permeability, and promote recovery of a blood-brain barrier function from a pathologically impaired state to a state close to a physiological barrier. Axitinib and an analog thereof reduce blood-brain barrier permeability by inhibiting the vascular endothelial cell growth factor-phosphatidylinositol kinase-protein kinase B signaling pathway and reducing the degree to which a blood-brain barrier tight junction protein Claudin-5/Occludin is down-regulated. The blood-brain barrier permeability regulator can be used in the treatment of a disease related to causing a change in blood-brain barrier permeability.

Use of Axitinib and analogs thereof in preparing blood-brain barrier permeability regulator

The present invention relates to use of SC79 or an analogue thereof in the preparation of a blood-brain barrier permeability regulator. The blood-brain barrier permeability regulator comprises SC79 or an analogue thereof as an active ingredient, which down-regulates expression of tight junction proteins Claudin-5 and Occludin by activating Claudin-5 and Occludin signaling pathway downstream the protein kinase B, and thereby increases the blood-brain barrier permeability, and enhances the efficiency of transportation of a brain targeting drug delivery system, especially, an Angiopep-2-modified glycolipid nano-delivery system, into the brain. The present invention also relates to a kit comprising the blood-brain barrier permeability regulator and a brain targeting drug delivery system. According to the present invention, use of the blood-brain barrier permeability regulator in combination with a brain targeting drug delivery system can enhance the efficiency of transportation of a brain targeting drug delivery system into the brain, and thereby improve the therapeutic efficacy of the brain targeting drug delivery system.

Blood-brain barrier permeability regulator and use thereof

The present invention provides a PEGylated and fatty acid grafted chitosan oligosaccharide comprising a structural unit represented by the following Formula (I) and a structural unit represented by the following Formula (II) and synthesize method, wherein the chitosan oligosaccharide has a molecular weight of less than 200,000 Da, and a degree of deacetylation of 70%-100%, and part of free amino groups of chitosan oligosaccharide chain are replaced by a fatty acid or PEG, where n refers to degree of polymerization of the PEG, and R is an alkyl group having 11-21 carbon atoms. The grafting ratio of fatty acids is 1%-50%, and the grafting ratio of PEG is 0.05%-50%. The present invention also comprise a pharmaceutical composition comprising the PEGylated and fatty acid grafted chitosan oligosaccharide as a carrier, and use of the PEGylated and fatty acid grafted chitosan oligosaccharide in preparation of a pharmaceutical composition. 

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Hangzhou, China

Fuqiang Hu