Preparation method of cationic liposome nanoparticles of amino acid

A cationic liposome and nanoparticle technology, which is applied to the preparation method of peptides, liposome delivery, and the preparation of organic compounds, can solve the problem of high synthesis cost of amino acid cationic liposomes, achieve efficient preparation, easy operation, low cost effect

Active Publication Date: 2011-05-18
湖南远泰生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Above-mentioned two synthetic methods all adopt palladium-carbon catalyst to realize reductive ammoniation, in addition method (2...

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  • Preparation method of cationic liposome nanoparticles of amino acid
  • Preparation method of cationic liposome nanoparticles of amino acid
  • Preparation method of cationic liposome nanoparticles of amino acid

Examples

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Embodiment 1

[0018] Example 1. Preparation of cationic liposome Glu-C12 and TMA-C2-Glu-C12 nanoparticles: Add L-glutamic acid (1.47 g, 10.0 mmol), lauryl alcohol ( 6.1 mL, 13.0 mmol), p-toluenesulfonic acid monohydrate (0.99 g, 5.0 mmol) and toluene (16 mL), the water trap was refluxed for about 6 h, until the reaction mixture became clear, TLC (ethyl acetate Ester: methanol = 5: 1) detection, the reaction is complete. The toluene was distilled off, the residue was dissolved in dichloromethane, washed successively with 5% aqueous sodium carbonate solution and distilled water, the organic phase was dried with anhydrous sodium sulfate, and dichloromethane was distilled off. The residue was dissolved in acetone, a small amount of dilute hydrochloric acid was added dropwise to the acetone solution, a white solid was precipitated, filtered by suction, and dried in vacuum to obtain L-glutamic acid dilauryl hydrochloride (3.94 g, 8.1 mmol, 81.9% ). 1 H NMR (500MHz, CDCl 3 ), d (ppm): 8.89 (s, ...

Embodiment 2

[0023] Example 2. Preparation of cationic liposome TMA-C2-Glu-C8 nanoparticles: Add L-glutamic acid (4.40 g, 30.0 mmol), n-octanol (12.2 mL, 78.0 mmol), p-toluenesulfonic acid monohydrate (5.00 g, 30.0 mmol) and toluene (30 mL), reflux water separation reaction, TLC (ethyl acetate: methanol = 5 : 1) detection, the reaction was complete after 6 h . Evaporate toluene, dissolve dichloromethane, wash with 5% sodium carbonate solution and distilled water successively, dry the organic phase with anhydrous sodium sulfate, and distill dichloromethane. Separation by column chromatography gave bis-n-octanol L-glutamate (6.43 g, 17.3 mmol, 57.9%).

[0024] L-bis-n-octanol glutamate (3.54 g, 9.5 mmol), dry dichloromethane (30 mL) and triethylamine (2.7 mL, 20.0 mmol) were successively added into a 100 mL round neck flask and stirred for 1 h . Chloroacetyl chloride (0.94 mL, 12.3 mmol) was slowly added, stirred at room temperature for 24 h, and TLC (petroleum ether: ethyl acetate = 5: 1...

Embodiment 3

[0027] Example 3 Preparation of cationic liposome TMA-C2-β-Ala-C12 nanoparticles: β-alanine (1.78 g, 20.0 mmol), lauryl alcohol (14.0 mL, 60.0 mmol), dry HCl gas was passed into the reaction solution, and TLC (ethyl acetate: methanol = 5: 1) detected that the reaction was complete after 12 h. Ethyl acetate was added to the reaction solution, and a white solid precipitated out, which was filtered by suction and dried in vacuo to obtain β-alanine lauryl ester (3.94 g, 10.6 mmol, 67.2%).

[0028] Add β-alanine lauryl ester (1.02 g, 3.4 mmol) into a 100 mL round-necked flask, add 35 mL of dry DMF and stir to dissolve, then add triethylamine (1.0 mL, 6.8 mmol), and stir for 1 h. Chloroacetyl chloride (0.3 mL, 4.1 mmol) was slowly added, stirred at room temperature for 8 h, and TLC (petroleum ether: ethyl acetate = 5: 1) detected that the raw material had reacted completely. Concentrate, dichloromethane and water solution, the organic layer is dried over anhydrous sodium sulfate, a...

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Abstract

The invention discloses a preparation method of amino acid cationic liposome nanoparticles. The method comprises the following steps: (1) adding amino acid which is used as a raw material into lauric acid or normal alcohol acid so as to be subjected to esterification reaction, separating and purifying to obtain white solid or paste; (2) after the esterification reaction in the step (1) is finished, dropping chloroacetyl chloride in the obtained solid slowly to be subjected to chloroacetylation reaction, concentrating the reactant, then adding trimethylamine to be subjected to quaternization reaction, and performing the corresponding separation and purification to the obtained white or colorless solid; and (3) performing ultrasonic oscillation water dispersion on the solid obtained in the step (2) to obtain the corresponding amino acid cationic liposome nanoparticles. The method provided by the invention has low cost, is easy to operate, is suitable for most of amino acids and can be used for efficiently preparing amino acid cationic liposome nanoparticles with different structures.

Description

technical field [0001] The invention relates to a method for preparing amino acid cationic liposome nanoparticles. Background technique [0002] With the advancement of life science technology and the development of bioengineering, nucleic acid and nucleic acid derivatives are widely used in the treatment of diseases due to their unique pharmacological effects. The core of nucleic acid drug therapy is to introduce nucleic acid drugs into specific cells and maintain their functions stably. However, due to the barrier of cell membranes, it is difficult for nucleic acid drug molecules to be directly transferred into cells. Even if nucleic acid drugs are transferred into cells, there are many problems such as virus recombination, carcinogenesis, immunity, etc., and their safety cannot be guaranteed; at the same time, nucleic acid drugs such as antisense nucleic acid, ribozyme, and RNA interference are easily degraded by nucleases in the body. The drug is unstable in the body an...

Claims

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Application Information

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IPC IPC(8): C07C229/24C07C227/18C07K5/023C07K5/062C07K5/027C07K1/113A61K9/127A61K48/00
Inventor 张健曾佑林苏胜培向双林孙玲玲汪涛何芳丽史明明胡翔
Owner 湖南远泰生物技术有限公司
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