Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tetrahexose monosialogandlioside-modified recombinant lipoprotein and application thereof

A ganglioside and monosialic acid technology, applied in the fields of neuropharmacology and chemical pharmacy, can solve the problems of difficult to improve the pathological manifestations of AD patients, neuron immune attack, aggravation, etc., to avoid the leakage of recombinant lipoprotein loaded drugs, The effect of not easy to gather

Inactive Publication Date: 2017-03-01
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
View PDF4 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, passive immunotherapy itself has some important problems: (1) Adverse reactions induced by Aβ-antibody immune complexes: Aβ, as an autoantigen, may induce secondary immune reactions after forming immune complexes with antibodies entering the brain And lead to inflammation of the central nervous system and damage to the blood vessel wall, causing adverse reactions such as inflammation in the brain, cerebral microvascular hemorrhage, and vasogenic cerebral edema; (2) currently effective antibodies are specific antibodies against the amino terminal of Aβ. The end sequence is located in the extracellular segment of Aβ precursor protein (APP), so these anti-Aβ amino-terminal antibodies will also bind to the APP of neurons and cause normal neurons to be immune attack
At the same time, the failure of clinical trials of Aβ antibodies including bapineuzumab has shown that although Aβ antibodies can effectively clear Aβ, they are less effective in improving cognitive function in AD patients
The possible reason is that the secondary pathological process triggered by Aβ aggregation, such as synaptic dysfunction and neuron loss, etc., once triggered, can aggravate the pathological process of AD independently of Aβ; clinically, when AD patients develop disease At the time of symptoms, the nervous system function has been irreversibly damaged. At this time, it is difficult to improve the pathological manifestations of AD patients if only focusing on the clearance of Aβ

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Tetrahexose monosialogandlioside-modified recombinant lipoprotein and application thereof
  • Tetrahexose monosialogandlioside-modified recombinant lipoprotein and application thereof
  • Tetrahexose monosialogandlioside-modified recombinant lipoprotein and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1. Monosialotetrahexosyl ganglioside modification improves the monodispersity of recombinant lipoproteins

[0046] (1) Preparation

[0047] 5%, 10%, 20% of the total lipid molar percentage of monosialotetrahexosyl ganglioside incorporated into 95%, 90%, 80% of the total lipid molar percentage of dimyristoylphosphatidylcholine In the alkali, add chloroform to dissolve, remove the organic solvent by rotary evaporation under reduced pressure, add pH7.4 phosphate buffer solution hydration to the lipid film, obtain monosialotetrahexosyl ganglioside modified liposome (lipid Total mass 4mg). Add 0.8 mg of ApoE, mix gently, place on a vibrating shaker at 100 rpm and incubate at 37° C. for 36 hours to obtain monosialotetrahexosylganglioside-modified recombinant lipoprotein.

[0048] (2) Characterization

[0049] Laser particle size analyzer measured the particle size and zeta potential. The results showed that the particle size of monosialotetrahexosyl ganglioside mod...

Embodiment 2

[0051] Example 2. Monosialotetrahexosyl ganglioside modification improves the Aβ affinity of recombinant lipoprotein pairs

[0052] (1) Preparation

[0053] 5%, 10%, 20% of the total lipid molar percentage of monosialotetrahexosylganglioside incorporated into 95%, 90%, 80% of the total lipid molar percentage of dipalmitoylphosphatidylcholine Medium (total lipid mass 4mg), ApoE 0.8mg, same as Example 1 to prepare monosialotetrahexosylganglioside modified recombinant lipoprotein.

[0054] Cardiolipin accounting for 5% of the total lipid molar percentage is incorporated into the dipalmitoylphosphatidylcholine (total lipid mass 4mg) accounting for 95% of the total lipid molar percentage, ApoE 0.8mg, the same as above to prepare cardiolipin modified recombinant lipid protein.

[0055] Accounting for 10% sulfatide in the total lipid molar percentage is incorporated into dipalmitoylphosphatidylcholine accounting for 90% total lipid molar percentage (total lipid mass 4mg), ApoE 0.8 ...

Embodiment 3

[0061] Example 3. Monosialotetrahexosyl ganglioside modification improves the uptake and degradation of Aβ by recombinant lipoprotein-mediated microglial cells

[0062] (1) Preparation

[0063] The monosialotetrahexosyl ganglioside accounting for 5% of the total lipid molar percentage is incorporated into the phosphatidylcholine and phosphatidic acid mixture (4 mg total lipid mass) accounting for 95% of the total lipid molar percentage, ApoE 0.4 mg, same as in Example 1 to prepare monosialotetrahexosylganglioside modified recombinant lipoprotein.

[0064] (2) Monosialotetrahexosylganglioside modified recombinant lipoprotein promotes the uptake of Aβ by primary microglia

[0065] FAM fluorescently labeled Aβ 1-42 Added to the 96-well plate planted with microglial cells, respectively, the recombinant lipoprotein and monosialotetrahexosylganglioside modified recombinant lipoprotein were diluted with DMEM and added to the 96-well plate planted with primary microglial cells plat...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
Login to View More

Abstract

The invention discloses tetrahexose monosialogandlioside-modified recombinant lipoprotein and an application of the tetrahexose monosialogandlioside-modified recombinant lipoprotein in preparation of a drug carrier and an application of the tetrahexose monosialogandlioside-modified recombinant lipoprotein in medicines for treating or preventing A-beta aggregation-relative disease. The tetrahexose monosialogandlioside with appropriate content is used for modifying the recombinant lipoprotein to obviously increase the affinity of the recombinant lipoprotein on beta amyloid protein, and promotes the removal of the beta amyloid protein; the tetrahexose monosialogandlioside-modified recombinant lipoprotein is taken as the multifunctional nano carrier for preventing and treating central nervous system disease, especially Alzheimer disease, and has very important research value and clinical application prospect.

Description

technical field [0001] The invention relates to the fields of neuropharmacology and chemical pharmacy, in particular to monosialotetrahexosyl ganglioside modified recombinant lipoprotein and its application in the preparation of drug carriers and the preparation of drugs for preventing and treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is the most common degenerative disease of the central nervous system that occurs in the elderly population and is characterized by progressive dementia. The clinical manifestations are deteriorating cognitive and memory functions, progressive decline in the ability of daily living, accompanied by various neuropsychiatric symptoms and behavioral disturbances. At present, the incidence of AD in the elderly population is second only to cardiovascular disease, cancer and stroke, and has become the fourth leading cause of death. With the intensification of population aging process, the incidence of such disea...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/42A61K47/26A61K45/00A61P25/28
CPCA61K9/0043A61K45/00A61K47/549A61K38/1716C07K14/775A61P25/16A61P25/28A61K47/26A61K47/42G01N33/6896
Inventor 高小玲黄萌陈红专宋清香
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products