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Cationic liposome with aliphatic acid as membrane material and preparation method and application thereof

A cationic liposome and cationic lipid technology, applied in the field of biomedicine, can solve the problems of further improvement of targeting, low liposome encapsulation rate, complicated preparation process, etc., so as to improve blood microcirculation and enhance memory. and thinking ability, the effect of simple preparation process

Active Publication Date: 2019-01-08
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The technical problem to be solved by the present invention is to provide a kind of cationic lipid with fatty acid as membrane material in order to overcome the defects of existing liposomes such as low encapsulation efficiency, poor stability, complex preparation process and further improvement of targeting performance. Plastid and its preparation method and application

Method used

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  • Cationic liposome with aliphatic acid as membrane material and preparation method and application thereof
  • Cationic liposome with aliphatic acid as membrane material and preparation method and application thereof
  • Cationic liposome with aliphatic acid as membrane material and preparation method and application thereof

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Effect test

Embodiment 1

[0059] The preparation of embodiment 1 fatty acid

[0060] 30.0 mg of 10-hydroxyoctadecanoic acid (0.1 mmol) was dissolved in 5 mL of dichloromethane, 84.8 mg of Dess-Martin oxidizer (DMP, 0.2 mmol) and 33.6 mg of sodium bicarbonate (0.4 mmol) were added. The mixed solution was stirred overnight at room temperature (25±5°C). Add 10.6 mL of saturated sodium thiosulfate to the mixed solution and continue to stir for 2 hours, then extract with ethyl acetate, dry the organic phase over anhydrous magnesium sulfate, concentrate under reduced pressure, and separate and purify the crude product by flash column chromatography to obtain 10-carbonyl octadecadecane Carbonic acid;

[0061] Collect 30.0 mg of 10-carbonyl octadecanoic acid (0.1 mmol), dissolve it in 2 mL of methanol, then add 61.6 mg of ammonium acetate (0.8 mmol), and react at room temperature for 1.5 hours. Add 4.8 mg of sodium cyanoborohydride (0.1 mmol) to the mixed solution, stir for 2 days, then extract with ethyl ac...

Embodiment 2

[0065] The preparation of embodiment 2 fatty acids

[0066] 30.0 mg of 10-hydroxyoctadecanoic acid (0.1 mmol) was dissolved in 5 mL of chloroform, and 42.414 mg of Dess-Martin oxidizer (DMP, 0.1 mmol) and 8.4 mg of sodium bicarbonate (0.1 mmol) were added. The mixed solution was stirred overnight at room temperature. Add 5.772 mL of saturated sodium thiosulfate to the mixed solution and continue to stir for 3 hours, then extract with ethyl acetate, dry the organic phase over anhydrous magnesium sulfate, concentrate under reduced pressure, and separate and purify the crude product by flash column chromatography to obtain 10-carbonyl octadecadeca Carbonic acid;

[0067] Collect 30.0 mg of 10-carbonyl octadecanoic acid (0.1 mmol), dissolve it in 2 mL of isopropanol, then add 7.708 mg of ammonium acetate (0.1 mmol), and react at room temperature for 1.5 hours. Add 4.8 mg of sodium cyanoborohydride (0.1 mmol) to the mixed solution, stir for 2 days, then extract with ethyl acetate...

Embodiment 3

[0071] Example 3 Structural Identification of 10-Amino Octadecanoic Acid and Fatty Acid

[0072] Utilize nuclear magnetic resonance spectrum to measure the 10-amino octadecanoic acid and fatty acid molecular structure that embodiment 1 prepares, obtain corresponding proton nuclear magnetic resonance spectrum figure and carbon nuclear magnetic resonance spectrum figure, as Figure 1-4 shown. The nuclear magnetic resonance spectroscopy determination method is a conventional technical means in the art, and will not be repeated here.

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Abstract

The invention discloses a cationic liposome with aliphatic acid as membrane material and a preparation method and an application thereof. The cationic liposome is provided with a membrane; the membrane comprises the aliphatic acid, cationic lipids and cholesterol. The cationic liposome with the aliphatic acid as the membrane material, disclosed by the invention, has the advantages of high efficiency, safety, stability, good targeted homogeneity, stable and reliable quality, simple and convenient preparation process and the like. As a nucleic acid drug cationic gene transfection reagent, the cationic liposome with novel aliphatic acid as a component has the advantages of obviously lowering cytotoxicity and obviously enhanced gene transfection efficiency when being compared with a commercialgene transfection reagent liposome 2000; and the cationic liposome with the aliphatic acid as the membrane material can be applied to the transfection of nucleic acid drugs as a novel lipoid gene carrier functional reagent.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a cationic liposome with fatty acid as a membrane material and a preparation method and application thereof. Background technique [0002] With the development of molecular biology and the completion of the Human Genome Project, gene therapy has gradually become a treatment method for major diseases that seriously threaten human health, such as genetic diseases, malignant tumors, AIDS, and cardiovascular and cerebrovascular diseases. This method is to introduce normal genes or genes with therapeutic effects into target cells in a specific way to correct gene defects and finally achieve the purpose of treating diseases. Compared with traditional treatment methods, gene therapy can specifically treat target cells and has long-term efficacy. However, since exogenous genes are easily degraded in whole or in part by nucleases after entering cells, the expression effic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/18A61K47/28A61K48/00A61P35/00
CPCA61K9/1277A61K47/18A61K47/186A61K47/28A61K48/0025A61K48/005A61P35/00
Inventor 彭丽华王毛泽
Owner ZHEJIANG UNIV
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