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Preparation and application of anti-Alzheimer disease (AD) peptide-metal-drug self-assembled nanoparticles

An Alzheimer's disease and nanoparticle technology, which is applied in the fields of drug combination, drug delivery, medical preparations with inactive ingredients, etc., can solve the problems of poor blood-brain barrier permeability, low bioavailability, and poor water solubility. Achieve the effects of low raw material price, high drug loading rate and rapid response

Active Publication Date: 2021-04-13
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs have defects such as extremely poor water solubility, easy oxidation, easy degradation, and poor permeability of the blood-brain barrier, resulting in extremely low bioavailability and little curative effect in AD treatment.

Method used

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  • Preparation and application of anti-Alzheimer disease (AD) peptide-metal-drug self-assembled nanoparticles
  • Preparation and application of anti-Alzheimer disease (AD) peptide-metal-drug self-assembled nanoparticles
  • Preparation and application of anti-Alzheimer disease (AD) peptide-metal-drug self-assembled nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] 1) Weigh 0.0043 g of Fmoc-Trp, dissolve it with an appropriate amount of Tris solution (1 M), add 900 µL of pure water, and disperse it evenly by ultrasonication to prepare 1 mL of 0.01 M Fmoc-Trp stock solution.

[0045] 2) Weigh 0.0055 g FeSO 4 , add 100 µL, dissolve HCl (0.1 M), add 900 µL pure water to make 0.02M FeSO 4 stock solution.

[0046] 3) Weigh 0.0121 g of Que, dissolve it in absolute ethanol solution, and prepare 1 mL of 0.02 M Que stock solution.

[0047] 4) Add 200 µL Fmoc-Trp stock solution to the reagent bottle, add 100 µL absolute ethanol, then add 20 µL 0.1 M Tris solution, add 50 µL FeSO 4 Add 50 µL of Que stock solution to the stock solution. At this time, the pH of the reaction solution is 7~8. Add water to make it 500 µL and react for 5 minutes. After centrifugation at 10,000 rpm, absorb the supernatant, add deionized water to continue centrifugation, and repeat. Washed three times with water, finally Fmoc-Trp-Fe 2+ -Que Nps is obtained by de...

Embodiment 2

[0066] 1) Weigh 0.005 g of Fmoc-Leu, dissolve it with an appropriate amount of Tris (1 M), add 900 µL of pure water, and disperse it evenly with ultrasound to prepare 1 mL of 5 mg / mL Fmoc-Leu stock solution.

[0067] 2) Weigh 0.0197 g MnCl 2 4H 2 O, add 10 mL pure water to make 0.01M MnCl 2 4H 2 O stock solution.

[0068] 3) Weigh 4 mg Cur, dissolve it in DMSO, and prepare 50 μL of 60 mg / mL Cur stock solution.

[0069] 4) First add 400 μL Fmoc-Leu stock solution to the reagent bottle, then add 200 μL MnCl under stirring at 900 rpm 2 4H 2 O stock solution, add 5 μL Tris (1 M), immediately add 10 µL Cur stock solution, add water to make the volume to 1 mL, at this time, the reaction solution pH=7~8, react for 5 minutes, centrifuge at 10000 rpm, absorb Add pure water to the supernatant, continue centrifuging, repeat washing three times, and rinse with pure water for the last time to obtain the product Fmoc-Leu-Mn 2+ -Cur Nps.

[0070] 1. The resulting Fmoc-Leu-Mn 2+ -Cur...

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Abstract

The invention discloses preparation and application of anti-Alzheimer disease (AD) peptide-metal-drug self-assembled nanoparticles, and belongs to the field of nano material preparation and biomedical application. The peptide-metal-drug nanoparticles are prepared in a self-assembly mode by taking coordination effect and hydrophobic effect as driving force. The peptide-metal-drug self-assembled nanoparticles have the advantages of being simple in preparation process, controllable in particle size and potential, good in water solubility, high in drug loading rate, good in biocompatibility, biodegradable and the like. The self-assembled nanoparticles show remarkable inhibition and degradation effects on A[beta] protein fibrosis, excellent ROS scavenging capacity, activity inhibition of beta-secretase and other functions at low dosage concentration, so that the peptide-metal-drug self-assembled nanoparticles have huge potentials as a multi-target and multi-channel drug for treating AD.

Description

technical field [0001] The invention belongs to the field of nanomaterial preparation and biomedical application, and in particular relates to the preparation and application of a peptide-metal-drug self-assembled nanoparticle. The self-assembled nanoparticle can significantly inhibit Aβ protein fibrosis at a low concentration. Inhibition and degradation effects, excellent ROS scavenging ability and β-secretase activity inhibition and other functions. Background technique [0002] Alzheimer's disease (AD for short), also known as senile dementia, is a degenerative disease of the central nervous system. Patients with the disease may experience severe memory loss, unstable mental state, and inability to take care of themselves in the later stage. It brings serious harm and burden to patients, their families and society. At present, AD is one of the five key prevention and treatment diseases verified by the World Health Organization in the 21st century. Therefore, the research...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/54A61K47/64A61K47/52A61K45/00A61K31/352A61K31/12A61P25/28
CPCA61K47/6929A61K47/542A61K47/64A61K47/52A61K45/00A61K31/352A61K31/12A61P25/28
Inventor 朱春玲杨宇恒王月雪
Owner FUZHOU UNIV
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