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Method for preparing antibody target modified Alzheimer disease targeted drug delivery compound and application of antibody target modified Alzheimer disease targeted drug delivery compound

A technology of Alzheimer's disease compound, which is applied in the field of preparation of Alzheimer's disease targeted drug delivery compound, to achieve the effect of improving bioavailability and long half-life

Inactive Publication Date: 2015-01-21
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The antibody-targeted modified Alzheimer's disease-targeted drug delivery complex involved in the present invention has no similar research reports at home and abroad

Method used

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  • Method for preparing antibody target modified Alzheimer disease targeted drug delivery compound and application of antibody target modified Alzheimer disease targeted drug delivery compound
  • Method for preparing antibody target modified Alzheimer disease targeted drug delivery compound and application of antibody target modified Alzheimer disease targeted drug delivery compound
  • Method for preparing antibody target modified Alzheimer disease targeted drug delivery compound and application of antibody target modified Alzheimer disease targeted drug delivery compound

Examples

Experimental program
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Effect test

Embodiment 1

[0030] Take hydrogenated soybean lecithin (PC), cholesterol (Cholesterol) and DSPE-mPEG2000 in a 1.5 ml EP tube, heat and dissolve in 0.3 ml ethanol solution (65°C), draw it into a 1 ml syringe; take 3 ml Heat 250 mM ammonium sulfate solution in a glass bottle at 65°C, add ginsenoside under magnetic stirring to dissolve completely; take out the syringe, slowly inject the oil phase in the syringe into the water phase, and stir magnetically for 10-15 minutes to form a ginsenoside-coated Liposomes: react overnight with thiolated antibodies and ginsenoside-coated liposomes at room temperature with stirring, the maleic anhydride active groups on the surface of the carrier react with thiolated antibodies, and finally use a 50K dialysis membrane to remove the free antibodies The antibody-targeted drug nanocarrier is prepared by dialysis.

Embodiment 2

[0032] Preparation of the test sample: Dilute the dialyzed targeted drug nanocarrier 10 times with MilliQ-water; take 0.5mL of the sample to be tested, add it to the sample pool, and confirm that there are no bubbles in the measurement container. Each sample was measured 3 times. The measurement conditions are: 170° scattering angle, 25°C.

Embodiment 3

[0034] Highly differentiated PC12 cells were seeded in a 96-well plate at a density of 5000 cells / well and incubated at 37°C with 5% CO2. Set up 0, 10, 15, 20, 25, 30 μM amyloid-treated experimental groups and a blank control, and set 3 replicate wells for each group. After 24 hours of amyloid treatment, add CCK-8 reagent, the volume ratio of medium:CCK-8 reagent is 10:1 (CCK-8 reagent 10 μL), shake well on the shaker, and incubate the cells in the incubator for 1.5 h. A microplate reader (TECAN Model Sa?re2) was used to measure the OD value of each well at a wavelength of 450 nm.

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Abstract

The invention relates to an antibody target modified Alzheimer disease targeted drug delivery compound. According to the compound, hydrogenated soybean lecithin and cholesterol form a phospholipid bilayer structure, distearoyl phosphoethanolamine-polyethylene glycol is interpenetrated in the phospholipid bilayer, water-soluble drugs are coated in lipidosome, and an antibody is modified on the surface of the lipidosome. The invention further relates to a preparation method and application of the targeted drug delivery compound. The targeted drug delivery compound has the advantages that a targeted nano-drug delivery system has excellent biocompatibility; hydrophilic drugs are coated in the bilayer lipidosome by means of physical effect; compared with a free drug, the targeted drug delivery compound has the beneficial effects of remarkably improving the drug target, prolonging the circulating time of the drug in a body and improving the biological utilization of the drug; and a non-invasive administration mode is provided to treatment of Alzheimer disease.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a method for preparing an antibody-targeted modified Alzheimer's disease-targeted drug delivery complex and its application. Background technique [0002] Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease, clinically manifested as deteriorating cognitive and memory functions, progressive decline in daily life ability, and various neuropsychiatric symptoms and behavioral disorders . As the aging society continues to intensify, more and more elderly people are beginning to suffer from Alzheimer's disease. At present, the number of people suffering from Alzheimer's disease in the world is nearly 30 million, and the number of patients is still increasing at a rate of 4.6 million per year. . The number of patients with dementia in my country is about 5 million, which is one of the countries with the largest number of dementia patients in the world. The...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/704A61K47/42A61K47/34A61P25/28
Inventor 李威柯长洪孙赟蒋成陈迪祝仙弟张付雷赵孟鑫
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY