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PEG2, n-lipid derivative modified nano-carrier, preparation method and application

A lipid derivative, nanocarrier technology, applied in the field of medicine, can solve the problems of severe allergy or allergic reaction, loss of curative effect, increase of clearance rate, etc.

Active Publication Date: 2021-09-07
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical experience with PEG chemotherapy has shown that anti-PEG antibodies not only increase clearance and loss of efficacy, but also cause severe allergic or anaphylactic reactions

Method used

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  • PEG2, n-lipid derivative modified nano-carrier, preparation method and application
  • PEG2, n-lipid derivative modified nano-carrier, preparation method and application
  • PEG2, n-lipid derivative modified nano-carrier, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] The first tail vein injection of DSPE-PEG with a total molecular weight of 2000Da 2000 DSPE-PEG with a total molecular weight of 2000Da of PEG injected into the tail vein of the modified emulsion for the second time 2000 The effect of modifying the drug-time curve of emulsion

[0068] Experimental animals:

[0069] Wistar rats (180~210g, (Provided by Lei Yunshang Pharmaceutical Laboratory Animal Center)

[0070] Dosing regimen:

[0071] Male Wistar rats, weighing 180-210 g, were randomly divided into two groups, one as the control group and the other as the experimental group, 6 rats in each group, and administered by tail vein injection. The control group was injected with 5% glucose solution for the first time, and the experimental group was injected with DSPE-PEG with a total molecular weight of 2000Da according to the phospholipid dose of 5 μmol / kg for the first time. 2000 Modifying emulsion. After the first injection, every 7 days, all groups were intravenou...

Embodiment 2

[0077] The first tail vein injection of DSPE-PEG with a total molecular weight of 2000Da 2,2k DSPE-PEG with a total molecular weight of 2000Da of PEG injected into the tail vein of the modified emulsion for the second time 2,2k The effect of modifying the drug-time curve of emulsion

[0078] Experimental animals:

[0079] Wistar rats (180-210g, ♂, provided by Leiyunshang Pharmaceutical Experimental Animal Center)

[0080] Dosing regimen:

[0081] Male Wistar rats, weighing 180-210 g, were randomly divided into two groups, and administered by tail vein injection. The control group was injected with 5% glucose solution for the first time, and the experimental group was injected with DSPE-PEG with a total molecular weight of 2000Da according to the phospholipid dose of 5 μmol / kg for the first time. 2,2k Modifying emulsion. After the first injection, every 7 days, all groups were intravenously injected with 5 μmol phospholipids / kg PEG with a total molecular weight of 2000 Da ...

Embodiment 3

[0086] The first tail vein injection of DSPE-PEG with a total molecular weight of 10000Da 2,10k DSPE-PEG with a total molecular weight of 10000Da PEG injected into the tail vein of the modified emulsion for the second time 2,10k The effect of modifying the drug-time curve of emulsion

[0087] Experimental animals:

[0088] Wistar rats (180-210g, ♂, provided by Leiyunshang Pharmaceutical Experimental Animal Center)

[0089] Dosing regimen:

[0090] Male Wistar rats, weighing 180-210 g, were randomly divided into two groups, and administered by tail vein injection. The control group was injected with 5% glucose solution for the first time, and the experimental group was injected with DSPE-PEG with a total molecular weight of PEG of 10000Da according to the phospholipid dose of 5 μmol / kg for the first time. 2,10k Modifying emulsion. Seven days after the first injection, all groups were intravenously injected with 5 μmol phospholipids / kg of DSPE-PEG with a total molecular wei...

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Abstract

The invention relates to a PEG2, n-lipid derivative modified nano-carrier, a preparation method and application, and belongs to the technical field of medicines. A method capable of eliminating an ABC phenomenon caused by a PEGylation nano-carrier is provided, a modification material used by the nano-carrier is a PEG2, n-lipid derivative of PEG2, n, and forms a compact hydration layer on the surface of the carrier, so that the physical stability and the biological stability of the carrier are improved. Besides, the PEG2, n-lipid derivative of PEG2, n is selected to modify the nano-carrier, so that the ABC phenomenon caused by the PEGylated nano-carrier can be eliminated, and the severe problem of the existing PEGylated carrier is greatly solved; and the in-vivo circulation time of the nano-carrier is also ensured, the defect of insufficient circulation time of many PEG substitute materials is overcome, and a firmer foundation is laid for clinical transformation of a PEGylated nano-preparation.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a new method capable of eliminating the phenomenon of accelerated blood clearance by PEGylated nanocarriers. Background technique [0002] In order to overcome the disadvantages of traditional nanocarriers, such as easy recognition and uptake by mononuclear phagocyte system (MPS), short blood circulation half-life, and poor targeting, researchers used PEG lipid derivatives to modify the surface of nanocarriers. , greatly improving the physical, chemical and biological stability of the carrier and drug, this process is called PEGylation (PEGylation). Since the 1990s, this technology has been widely used in the field of nanocarrier surface modification. Although more and more studies have shown that other synthetic hydrophilic polymers used for surface modification can exhibit long-cycle properties similar to PEGylation, PEG has unique advantages such as low toxicity,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/24A61K9/127B82Y5/00B82Y40/00
CPCA61K47/24A61K9/1271A61K9/0019B82Y5/00B82Y40/00
Inventor 邓意辉刘敏李杰闫娜赵丹刘梦阳张红霞汤雪莹宋艳志刘欣荣
Owner SHENYANG PHARMA UNIVERSITY
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