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ROS responsive bionic nanoparticles for improving oxidation microenvironment and preparation method thereof

A biomimetic nano-responsive technology, applied in the fields of nanomedicine and biomedicine, can solve the problems of limited clinical application, inability to produce curative effect, and bioavailability less than 10%, so as to inhibit inflammation, improve pathological microenvironment, and improve biological The effect of utilization

Active Publication Date: 2021-04-20
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But these drugs are poorly absorbed, bioavailability is less than 10%
Therefore, no obvious curative effect can be produced, and its clinical application is very limited

Method used

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  • ROS responsive bionic nanoparticles for improving oxidation microenvironment and preparation method thereof
  • ROS responsive bionic nanoparticles for improving oxidation microenvironment and preparation method thereof
  • ROS responsive bionic nanoparticles for improving oxidation microenvironment and preparation method thereof

Examples

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preparation example Construction

[0037] A method for preparing a ROS-responsive polymer material, comprising the steps of:

[0038] (1) Polyester monomers are polymerized to obtain polyesters with an average molecular weight of 8,000-100,000 under the action of initiators and catalysts;

[0039] (2) prepare polyester-Ar-OH with the polyester that step (1) obtains as raw material; Synthesize PEG-Ar-OH with the PEG of average molecular weight 2000-6000,

[0040] (3) PEG-Ar-OCOCOCl is obtained by reacting PEG-Ar-OH with excess oxalyl chloride;

[0041] (4) Excessive PEG-Ar-OCOCOCl reacts with polyester-Ar-OH to obtain a ROS-responsive polymer material;

[0042] The Ar is a benzene ring (Ph) or a biphenyl ring (Ph-COO-Ph) connected by an ester bond.

[0043]The molar ratio of the polyester monomer, initiator and catalyst is (6000-100000):(50-200):1.

[0044] The polyester monomer is at least one of glycolide, lactide, glycolic acid, hydroxypropionic acid, hydroxybutyric acid, succinic acid, butanediol, valerol...

Embodiment 1

[0049] A kind of preparation method of ROS responsive polymer material (see figure 1 ), including the following steps:

[0050] (1) Mix polyester monomers (lactide ① and glycolide ② with a molar ratio of 3:1), initiator inositol and catalyst stannous octoate into the polymerization tube, and repeat vacuuming to seal the polymerization tube , first heated to 250°C with a heating mantle to melt inositol, and then placed in a 160°C oven for polymerization reaction for 8 hours to obtain polylactic acid polyglycolic acid (6S-PLGA③) with an average molecular weight of 8000. The crude product was purified and reprecipitated for 3 times, vacuum dried to constant weight;

[0051] The molar ratio of the polyester monomer, initiator and catalyst is 6000:50:1;

[0052] (2) 6S-PLGA-Ph-OH④ was prepared from 6S-PLGA obtained in step (1); PEG-Ph-OH⑦ was synthesized from PEG⑤ with an average molecular weight of 4000.

[0053] Dissolve 2mmol of p-hydroxybenzoic acid and 2mmol of N,N-dimethyl...

Embodiment 2

[0065] A method for preparing a ROS-responsive polymer material, comprising the steps of:

[0066] (1) Mix the polyester monomer glycolic acid, the initiator ethylene glycol and the catalyst stannous isooctanoate in the polymerization tube, repeat vacuuming to seal the polymerization tube, and place it in an oven at 150°C for 6 hours to obtain an average molecular weight of 20,000 The polyglycolic acid (PGA) of crude product was purified, reprecipitated 3 times, and vacuum-dried to constant weight;

[0067] The molar ratio of polyester monomer, initiator and catalyst is 34500:100:1;

[0068] (2) Prepare PGA-Ph-COO-Ph-OH by using the PGA obtained in step (1) as a raw material; synthesize PEG-Ph-OH with PEG with an average molecular weight of 2000.

[0069] Dissolve 8mmol p-hydroxybenzoic acid and 8mmol DMF in 20mLTHF to obtain solution 1; dissolve 8mmol oxalyl chloride in 20mLTHF, drop into solution 1; add 0.8mmol PGA and 2mmol triethylamine, stir at room temperature for 8h; ...

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Abstract

The invention discloses ROS responsive bionic nanoparticles for improving an oxidation microenvironment and a preparation method thereof. The preparation method comprises the steps of immersing cells in a hypotonic solution, centrifuging, ultrasonically treating and freeze-drying to obtain a nanoscale cell membrane; preparing a medicine into a solution I, preparing an ROS responsive polymer material into a solution II, and dropwise adding the solution I into the solution II while carrying out ultrasonic treatment to obtain a mixed solution; adding an emulsifier aqueous solution and the nanoscale cell membrane into a container, and ultrasonically dropping into the mixed solution; and volatilizing the solvent, centrifuging, washing with water, and freeze-drying to obtain the product. The method is simple and low in cost. The ROS response sensitivity is high, the ROS level is reduced, inflammatory response is inhibited, and therefore the pathological microenvironment is improved. The nanoparticles can be more phagocytized by macrophages, excessive ROS and inflammatory factor expression in the cells are reduced, and the bioavailability is high. Animal experiments prove that the nanoparticles have a better disease treatment effect than free drugs, and show a synergistic effect.

Description

technical field [0001] The invention relates to a ROS-responsive biomimetic nanoparticle for improving an oxidative microenvironment and a preparation method thereof, belonging to the fields of biomedicine and nanomedicine. Background technique [0002] Reactive oxygen species (ROS) regulate cellular homeostasis and participate in the pathophysiology of disease as master regulators of cellular dysfunction. Diseases associated with inflammatory signaling and metabolic dysfunction, such as atherosclerosis, ischemic diseases, diabetes, inflammatory diseases, are associated with altered redox balance. ROS act as central regulators of inflammatory signals, especially in the regulation of NF-κB activation and inflammasome signaling. Canonical NF-κB signaling is associated with insulin resistance, obesity and atherosclerosis. [0003] Animal studies clearly demonstrate that ROS are a viable target for therapeutic intervention in cardiovascular disease. However, the results of cl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K31/10A61K31/155A61K31/40A61K31/405A61K31/616A61K47/46A61K47/34A61P3/00A61P3/06A61P29/00A61P39/06
Inventor 杨菁梁晓玉李轩领李慧洋
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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