Application of phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme in preparation of medicine for treating acute kidney injury

An acute kidney injury and polyethylene glycol technology, applied in the application field of nano-biological materials, can solve the problems of increased ROS content in the kidney, acute kidney injury, etc., to prolong systemic circulation time, inhibit cell apoptosis, and have high biological safety Effect

Inactive Publication Date: 2021-01-29
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cisplatin often leads to an increase in ROS content in the kidney during chemotherapy for cancer, causing severe acute kidney injury

Method used

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  • Application of phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme in preparation of medicine for treating acute kidney injury
  • Application of phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme in preparation of medicine for treating acute kidney injury
  • Application of phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme in preparation of medicine for treating acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Synthesis of ultra-small cerium oxide nanozyme modified with phospholipid polyethylene glycol

[0051] (1) Synthesis of ultra-small cerium oxide nanozymes:

[0052] Add 0.4g of cerium acetate hydrate and 3.2g of oleylamine to 15ml of xylene, raise the temperature to 90 degrees Celsius at a rate of 2 degrees Celsius per minute, and stir for 4 hours to form a complex; inject 1ml of deionized water into an inert gas In the protection reaction system, aging for three hours, precipitation with anhydrous ether, and centrifugation to obtain ultra-small cerium oxide nanozyme.

[0053] The result is as figure 1 As shown, the ultra-small cerium oxide nanozyme was characterized by transmission electron microscopy, and the particle size was about 1-10 nm.

[0054] (2) Synthesis of ultra-small cerium oxide nanozyme modified with phospholipid polyethylene glycol:

[0055] Add 0.01 g of polyethylene glycol phosphate and 1 ml of ultra-small cerium oxide nanozyme to 5 ml o...

Embodiment 2

[0058] Example 2: Effect of Cerium Oxide Nanozyme on HK-2 Damage Caused by Cisplatin

[0059] Preparation of the drug: the phospholipid polyethylene glycol-modified ultra-small cerium oxide nanozyme prepared in Example 1 was selected and dispersed in an aqueous solution to obtain a final ultra-small cerium oxide nanozyme concentration of 8.3 mg / ml.

[0060] Cell model establishment: add cisplatin-containing cell culture medium to HK-2 cells, and redisperse with cell culture medium to obtain the drug at a concentration of 200 mM.

[0061] Group settings:

[0062] a. Control group: normal cells were given fresh culture medium.

[0063] b. Model group: only cell culture solution containing cisplatin was added to HK-2 cells to make the final concentration 10 μM.

[0064]c. Treatment group: Add 200mM cisplatin to HK-2 cells and add cerium oxide with different concentration gradients to the cell culture medium, and make the final concentrations of cerium oxide 0.78μM, 1.56μM, 3.13...

Embodiment 3

[0066] Example 3: Effect of cerium oxide nanozyme on cisplatin-induced acute kidney injury

[0067] 20-22g male ICR mice were taken and induced with cisplatin to establish AKI model. First, the mice were randomly divided into 4 groups, blank control group, cisplatin model group, cisplatin model group + cerium oxide 0.5m / kg administration group, cisplatin model group + cerium oxide 1.5m / kg administration group, each group 6 only. Intraperitoneal injection of 15mg / kg cisplatin, while tail vein injection of 0.5mg / kg or 1.5mg / kg cerium oxide nanozyme. On the third day of administration, the rats were dissected, and blood was collected from the eyeballs to collect serum. After dissecting, the heart was perfused, and the kidneys of the mice were removed for paraffin embedding, HE staining and TUNEL staining.

[0068] The result is as Figure 5 and Figure 6 It has been shown that cisplatin induces a significant increase in serum urea nitrogen and creatinine and increases in rena...

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Abstract

The invention discloses application of a phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme in preparation of a medicine for treating acute kidney injury. The acute kidneyinjury is induced by cis-platinum when cis-platinum is used for treating solid cancer. The phospholipid polyethylene glycol modified subminiature cerium oxide nano-enzyme provided by the invention can present activities of various antioxidant mimic enzymes, can play an efficient catalase activity in a physiological environment, effectively reduces the ROS level by acting on an Nrf2/Keap1 pathway,inhibits cell apoptosis, exerts important protection and treatment effects on acute kidney injury caused by cis-platinum, and is a more promising nanomaterial for low-toxicity anti-tumor applicationand development cis-platinum in clinical practice.

Description

technical field [0001] The invention relates to the application of nano-biological materials, in particular to the application of a phospholipid polyethylene glycol-modified ultra-small cerium oxide nano-enzyme in the preparation of medicines for treating acute kidney injury. Background technique [0002] Drug-induced renal injury refers to the renal injury caused by the drug itself or its metabolites after the use of one or several drugs. Drug-induced kidney injury can manifest as any type of acute or chronic kidney disease currently known. Acute kidney injury (Acute kidney injury, AKI) refers to the sudden decline of renal function, which may be accompanied by oliguria or anuria. The clinical syndrome of a sharp decline or loss in the body, manifested in the imbalance of water and electrolytes in the body, the accumulation of metabolites that cannot be ruled out, and the occurrence of hypomagnesemia and other symptoms. Its main cause is ischemia, nephropathy caused by th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/44A61K33/244A61K47/24A61K47/10A61K33/243A61P13/12A61P35/00
CPCA61K38/44A61K33/244A61K47/24A61K47/10A61K33/243A61P13/12A61P35/00C12Y111/01006A61K2300/00
Inventor 凌代舜翁勤洁李方园方春燕孙恒王金成谢安夏凡邱月萍
Owner ZHEJIANG UNIV
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