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Method for eliminating ABC (accelerated blood clearance) phenomenon of PEGtion nano-carrier

A nano-carrier and phenomenological technology, applied in the field of medicine, can solve the problems of weakening the long-term circulation advantages of PEGylated nano-carriers, toxic and side effects, etc.

Inactive Publication Date: 2014-05-21
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The emergence of this problem will not only greatly weaken the long-term circulation advantages of PEGylated nanocarriers, but also cause serious toxic and side effects in vivo due to changes in the pharmacokinetic behavior of encapsulated drugs and genes.

Method used

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  • Method for eliminating ABC (accelerated blood clearance) phenomenon of PEGtion nano-carrier
  • Method for eliminating ABC (accelerated blood clearance) phenomenon of PEGtion nano-carrier
  • Method for eliminating ABC (accelerated blood clearance) phenomenon of PEGtion nano-carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] : The drug-time curve of the first tail vein injection of DSPE-PEG modified emulsion with methoxy (OCH3) and hydroxyl (OH) end groups and the second tail vein injection of DSPE-PEG modified emulsion with methoxy (OCH3) end groups influences

[0052] Experimental animals:

[0053] Wistar rats (180-210 g, ♂, Experimental Animal Center of Shenyang Pharmaceutical University)

[0054] Dosing regimen:

[0055] 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 a phospholipid dose of 5 μmol kg for the first time. -1 The injection end group is methoxyl (OCH 3 ), hydroxyl (OH) DSPE-PEG modified emulsion. Seven days after the first injection, all groups were intravenously injected with 5 μmol phospholipid / kg PEGylated emulsion with a methoxyl group at the end, and were administered 1 m...

Embodiment 2

[0060] Drug-time curves of the first foot subcutaneous injection of DSPE-PEG modified emulsion with methoxyl (OCH3) and hydroxyl (OH) end groups versus the second tail vein injection of DSPE-PEG modified emulsion with methoxyl (OCH3) end groups influences

[0061] Experimental animals:

[0062] Wistar rats (180-210 g, ♂, Experimental Animal Center of Shenyang Pharmaceutical University)

[0063] Dosing regimen:

[0064] Male Wistar rats, weighing 180-210 g, were randomly divided into two groups, and subcutaneously injected into the feet. The control group was injected with 5% glucose solution for the first time, and the experimental group was injected with a phospholipid dose of 5 μmol kg for the first time. -1 The subcutaneous injection of the foot is methoxyl (OCH 3 ), hydroxyl (OH) DSPE-PEG modified emulsion. 7 days after the first injection, all groups were injected with 5 μmol phospholipid / kg PEGylated emulsion with methoxyl terminal group through the tail vein, an...

Embodiment 3

[0068] Example 3: The drug-time curve of the first tail vein injection of DSPE-PEG modified emulsion with carboxyl (COOH2000) and hydroxyl (OH) end groups and the second tail vein injection of DSPE-PEG modified emulsion with methoxyl (OCH3) end groups Impact

[0069] Experimental animals:

[0070] Wistar rats (180-210 g, ♂, Experimental Animal Center of Shenyang Pharmaceutical University)

[0071] Dosing regimen:

[0072] 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 a phospholipid dose of 5 μmol kg for the first time. -1Inject DSPE-PEG modified emulsion with carboxyl (COOH2000) and hydroxyl (OH) terminal groups. Seven days after the first injection, all groups were intravenously injected with 5 μmol phospholipid / kg PEGylated emulsion with a methoxyl group at the end, and were adm...

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Abstract

The invention discloses a novel means for eliminating the ABC (accelerated blood clearance) phenomenon of a PEGtion nano-carrier. A nano-carrier is modified by using a PEG-lipid derivative with the PEG end group (OH) being hydroxy, and is formed by connecting PEG with hydroxy as the end group and phospholipid through one of amido bond, ether bond, ester bond and disulfide bond. The nano-carrier comprises an emulsion, micelles, micro-capsules, microspheres and nano-particles. According to the means, the phenomenon of 'accelerated blood clearance' (ABC) of an existing PEGtion nano-carrier can be eliminated, and a compact hydration layer is formed on the carrier surface, so that the physical stability of the carrier can be improved, and the biological stability of the carrier can be improved.

Description

technical field [0001] The invention belongs to the technical field of medicine and discloses a new method capable of eliminating the phenomenon of PEGylated nano-carrier ABC. Background technique [0002] As a drug delivery system, nanocarriers have the advantages of improving drug therapeutic index, reducing drug side effects, and reducing drug dosage, making them popular in the fields of biomedicine and pharmacy. However, traditional nanocarriers are easily recognized and taken up by cells of the mononuclear-phagocyte system (MPS), resulting in a very short half-life in blood circulation, which prevents the drug from reaching the target site and exerting its effect effectively. To some extent, it limits its clinical application. widely used. In 1990, Blume et al. and Klibanov et al. found that polyethylene glycol-lipid (PEG-lipid) derivatives could increase the in vivo and in vitro stability of their modified liposomes. This discovery injected new vitality into the fur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/10A61K9/16A61K9/50
Inventor 邓意辉王春玲程晓波唐文雅裴莹李洁佘振南
Owner SHENYANG PHARMA UNIVERSITY
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