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Cationic lipid compound as well as preparation method and application thereof

A technology of cationic lipids and compounds, applied in the direction of steroids, chemical instruments and methods, and other methods of inserting foreign genetic materials, can solve the problems of high cytotoxicity, high price, and low cell transfection rate, and achieve transfection Strong dyeing ability, high biocompatibility, and simple preparation process

Active Publication Date: 2016-12-07
INNER MONGOLIA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with viral delivery methods, the use of non-viral nucleic acid delivery can avoid side effects such as immune stimulation and carcinogenesis. However, at present, non-viral nucleic acid vectors generally have problems such as low cell transfection rate, high cytotoxicity, and high price.

Method used

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  • Cationic lipid compound as well as preparation method and application thereof
  • Cationic lipid compound as well as preparation method and application thereof
  • Cationic lipid compound as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0060] The synthesis of embodiment 1 raw material

[0061] Synthesis of compound I (saturated / unsaturated aliphatic hydrocarbon amide of glutamic acid): dissolve saturated / unsaturated hydrocarbon-based ammonia or alcohol, Boc-glutamic acid-OH in a dry organic solvent, and add a condensing agent under nitrogen protection , after stirring at 0-35°C for 12-24 hours, distill off the organic solvent, add excess acid mixture, stir at room temperature for 1-2 hours, distill off the solvent, and use silica gel column chromatography to separate and purify the intermediate glutamic acid Saturated / unsaturated hydrocarbyl substituted esters or amides with a yield of 70%.

[0062] Synthesis of compound II (saturated / unsaturated aliphatic hydrocarbon amide of aspartic acid): dissolve saturated / unsaturated hydrocarbon-based ammonia or alcohol, Boc-aspartic acid-OH in a dry organic solvent, add under nitrogen protection Condensing agent, stir at 0-35°C for 12-24 hours, distill off the organi...

Embodiment 2

[0063] The synthesis of embodiment 2 raw materials

[0064] Synthesis of Compound III (Boc-protected peptidomimetics):

[0065] The first step: Stir Boc-ornithine and Boc-ornithine (Boc)-OSu in an organic solvent under alkaline conditions at 0-35°C for 24-36 hours, distill off the organic solvent and use silica gel column chromatography The intermediate Boc-ornithine (Boc)-ornithine (Boc)-COOH is obtained by separation and purification by the method, and the Boc is di-tert-butyl carbonate. Yield: 60%.

[0066] The second step: Stir the intermediate, N-hydroxysuccinimide, and condensing agent obtained in the first step in an organic solvent for 12 hours, then add Boc-ornithine, and continue stirring at 0-35°C for 12-24 hours After the organic solvent was distilled off, the compound II, Boc-Ornithine (Boc)-Ornithine (Boc)-Ornithine (Boc)-COOH, was obtained by separation and purification by silica gel column chromatography. The Boc is di-tert-butyl carbonate. Yield: 65%.

[...

Embodiment 3

[0074] Embodiment 3 The preparation of compound of the present invention (1)

[0075]

[0076] Raw materials include compound I (glutamic acid fatty alkane amide molecule), compound III (amino Boc-protected short peptide molecule), condensation agent (1-ethyl-(3-dimethylaminopropyl) carbodiimide salt Acid EDCI), base (N,N-diisopropylethylamine DIPEA) dissolved in dry dichloromethane, compound I: compound III: condensing agent: base (molar ratio) = 1:1:2:2 , The amount of solvent is limited to the complete dissolution of compound I, compound III, condensing agent and base.

[0077] Under the protection of nitrogen, the mixture was cooled to 0°C with an ice bath and then stirred at 25°C for 24 hours. After the reaction was over, the reaction mixture was dissolved in dichloromethane, washed 3 times with 5% citric acid solution, water, and saturated brine successively, dried with anhydrous sodium sulfate, and then purified by silica gel column chromatography (eluent: dichlorom...

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Abstract

The invention provides a cationic lipid compound as well as a preparation method and application thereof, and belongs to the field of preparation of non-virus gene carriers. The chemical structure of the cationic lipid compound is as shown in a general formula (I) (as shown in the description). The compound disclosed by the invention, and DOPE or DOPC or lecithin are mixed according to a mole ratio of the compound to the DOPE or the DOPC or the lecithin being (3-1) to (1-3), a mixture is dissolved in chloroform to be used for preparing a liposome gene carrier, and the carrier is uniform in particle size, good in dispersity, low in preparation cost, low in cytotoxicity and high in transfection foreign gene capacity. The compound disclosed by the invention can be used as a raw material for preparing a gene carrier, the problems of low cell transfection efficiency, large cytotoxicity, high price and the like, generally existing in non viral nucleic acid carriers at present are solved, and the compound has good market application prospects.

Description

technical field [0001] The invention belongs to the field of gene carrier preparation and application, and in particular relates to a cationic lipid compound, its preparation method and its application in the preparation of gene carrier. Background technique [0002] Nucleic acid transfection refers to the introduction of exogenous nucleic acid (including plasmid [plasmid DNA], small interfering RNA [siRNA], antisense nucleic acid [antisense nucleic acids], microRNA [microRNA], etc.) Play biological functions, so as to achieve the purpose of regulating gene expression. [0003] Gene therapy refers to the introduction of target genes (usually plasmid DNA) into cells to make them express active proteins, thereby treating diseases caused by gene mutations or gene defects. For example, lipoproteinase esterase deficiency is caused by a genetic mutation; Glybera, an adenovirus (AVV)-like gene drug carrying a wild-type lipoproteinase esterase gene, is capable of delivering the nor...

Claims

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Application Information

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IPC IPC(8): C07K7/02C07J41/00C12N15/88A61K47/28A61K47/18A61K48/00
Inventor 胡日查海小
Owner INNER MONGOLIA UNIVERSITY
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