Novel chemical restructuring high-density lipoprotein drug carrying system with targeted and double anti-tumor effects and application

A high-density lipoprotein and drug-carrying system technology, applied in the field of recombinant high-density lipoprotein carriers, can solve the problems of recombinant HDL that have not been reported and the physical stability of rHDL reduced

Inactive Publication Date: 2012-08-01
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This binding method is likely to cause apoA-I aggregation, making the negatively charged amino acid residues in the α-helical structure gather and repel each other, resulting in a decrease in the physical stability of rHDL
[0004] Although the use of recombinant HDL as a carrier of anti-tumor drugs has been reported in literature and patents, how to prepare recombinant HDL with high stability in vivo has not yet been reported.

Method used

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  • Novel chemical restructuring high-density lipoprotein drug carrying system with targeted and double anti-tumor effects and application
  • Novel chemical restructuring high-density lipoprotein drug carrying system with targeted and double anti-tumor effects and application
  • Novel chemical restructuring high-density lipoprotein drug carrying system with targeted and double anti-tumor effects and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The composition of the prescription is as follows: Paclitaxel: 0.01g

[0021] Egg phospholipids: 0.2g

[0022] Modified Cholesterol: 0.02g

[0023] Sodium cholate: 0.02g

[0024] apoA-I: 0.2g

[0025] Organic Phase: Ethanol

[0026] Hydration medium: PBS buffer pH 7.4

[0027] Preparation process: put the prescribed amount of medicine, egg phospholipid, and modified cholesterol in a vial, add an appropriate amount of ethanol, dissolve it by ultrasonication, transfer it into an eggplant-shaped bottle, place it in a rotary evaporator, remove the organic phase under reduced pressure, and vacuum Dry, add an appropriate amount of hydration medium dissolved with sodium cholate, ultrasonically disperse evenly into a translucent suspension, and then use a probe to ultrasonically pulverize to make it a transparent and opalescent liquid, pass through a 0.22 μm filter membrane, add apolipoprotein, After dissolving, place in a refrigerator at 4°C, stir magnetically at 600 rpm ...

Embodiment 2

[0029] The composition of the prescription is as follows: Paclitaxel: 0.01g

[0030] Egg phospholipids: 0.2g

[0031] Modified cholesterol 0.02g

[0032] Sodium cholate: 0.01g

[0033] Sodium lauryl sulfate: 0.01g

[0034] apoA-I: 0.2g

[0035] Organic Phase: Ethanol

[0036] Hydration medium: PBS buffer pH 7.4

[0037] The preparation process is the same as in Example 1. The average particle size of the prepared rHDL is 55nm, the encapsulation efficiency is 85.07%, and the protein binding rate is 45.9%.

Embodiment 3

[0039] The composition of the prescription is as follows: Paclitaxel: 0.01g

[0040] Egg phospholipids: 0.2g

[0041] Sodium cholate: 0.02g

[0042] Cholesterol modified apoA-I: 0.3g

[0043] Organic Phase: Ethanol

[0044] Hydration medium: PBS buffer pH 7.4

[0045] Preparation process: put the prescribed amount of medicine and egg phospholipids in a vial, add an appropriate amount of ethanol, dissolve it with ultrasound, transfer it into an eggplant-shaped bottle, place it in a rotary evaporator, remove the organic phase under reduced pressure, dry it in vacuum, add Appropriate amount of hydration medium dissolved with sodium cholate, ultrasonically dispersed into a translucent suspension, and then ultrasonically crushed with a probe to make it a transparent and opalescent liquid, passed through a 0.22 μm filter membrane, and dissolved by adding cholesterol-modified apolipoprotein Afterwards, place in a refrigerator at 4°C, stir magnetically at 600 rpm for 5 hours, and ...

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Abstract

The invention relates to the technical field of medicine, in particular to a novel chemical restructuring high-density lipoprotein structure, which is used as an anti-tumor drug carrier and is characterized by improving stability of a restructuring high-density lipoprotein carrier under the action of metabolic enzymes, blocking nutrient substances required by multiplication of tumor cells by utilizing the role that high-density lipoprotein transfers the drug in a targeted mode to gland tumor cells and the role that mediate cholesterol flows out, and improving toxic effect of the anti-tumor drug on tumor cells.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to the preparation and characterization of a novel chemically recombined high-density lipoprotein carrier for anti-tumor drugs, and in particular to a recombinant high-density lipoprotein carrier that cooperates with drugs to exert anti-tumor effects. It is characterized in that a new type of recombinant high-density lipoprotein is prepared, and it is used as an anti-tumor drug carrier, and the effect of high-density lipoprotein-mediated cholesterol efflux is used to block the nutrients required for tumor cell proliferation and enhance the anti-tumor drug effect on tumors. Cytotoxicity, and the use of chemical recombination to improve the stability of high-density lipoprotein carriers. Background technique [0002] High-density lipoprotein (high density lipoprotein, HDL) is a biologically active substance composed of apolipoprotein, free cholesterol, phospholipids and non-polar lip...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K9/19A61K47/42A61K47/24A61K47/28A61P35/00
Inventor 刘建平贾俊婷樊永庆
Owner CHINA PHARM UNIV
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