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Mannose derivative cation liposome nanoparticle preparation method

A cationic liposome and nanoparticle technology, which is applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., can solve the problems of gene non-integration, the risk of uncontrollable virus replication, inherent immunogenicity, application limitations, etc.

Inactive Publication Date: 2016-05-18
HUNAN NORMAL UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Commonly used gene carriers include viral vectors and non-viral vectors. Viral vectors have high transduction efficiency, the complex assembly process is completed by cells, and different viral vectors have different expression characteristics. However, due to the risk of uncontrollable viral replication and inherent immunogenicity , which limits its application; compared with viral vectors, non-viral vectors have the advantages of low toxicity, low immune response, and the genes they carry are not integrated into the host cell genome, etc.

Method used

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  • Mannose derivative cation liposome nanoparticle preparation method
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  • Mannose derivative cation liposome nanoparticle preparation method

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Experimental program
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Effect test

Embodiment 1

[0033] Embodiment 1. Mannose derivative cationic liposome di -C 12 - Preparation of Man-TMA nanoparticles:

[0034] Acetic anhydride (100.0 mL, 1.0 mol) was added into a 1.0 L three-necked flask, stirred by magnetic force, and cooled to 0 in an ice bath. o C, add HClO dropwise 4 (0.5 mL). Control temperature is less than 20 o C, Add mannose (25.0 g, 138.8 mmol) in portions. After the addition, it was naturally raised to room temperature, and the reaction was continued until TLC (petroleum ether: ethyl acetate = 2:1, volume ratio) showed that the reaction was basically completed, and a yellow transparent mixed solution was obtained. DCM (300.0 mL) was added to the reaction mixture, and the reaction mixture was poured into a beaker filled with ice-water mixture for liquid separation. The organic phase was washed two more times with cold water. The organic phase was anhydrous Na 2 SO 4 Dry, filter, concentrate, and vacuum-dry to give a brownish-yellow syrup 1,2,3,4,6-pen...

Embodiment 2

[0045] Embodiment 2. Mannose derivative cationic liposome di -C 14 - Preparation of Man-TMA nanoparticles:

[0046] Add 3'-azidopropyl 4,6- O -Benzylidene-α-D-mannopyranoside (1.5g, 4.8mmol), then dissolved in DMF (50.0mL), then added NaH (1.0g, 25.8mmol) and bromotetradecane (4.7mL ,17.2mmol,). Stirring reaction at room temperature, TLC (V 石油醚 :V 乙酸乙酯 =15:1) Monitor the reaction until there is no significant change. DCM (20.0 mL) was added to the reaction mixture solution, washed with water three times, and the organic phase was washed with anhydrous Na 2 SO 4 Dry, filter and concentrate. Through column chromatography (eluent: V 石油醚 :V 乙酸乙酯 =16:1) Separated and purified to obtain colorless syrup 3'-azidopropyl 2,3-di- O - n-tetradecyl-α-D-mannopyranoside (1.5 g, 46.9%). 1 HNMR (500MHz, CDCl 3 ): δ(ppm)7.53-7.32(m,5H,C 6 H 5 ),5.60(s,1H,C 6 h 5 C H ),4.81(d,1H, J 1,2 =1.0Hz,H-1),4.24(dd,1H, J 6a,5 =5.0Hz, J 6a,6b =10.0Hz,H-6a),4.05(dd,1H J 4,3 =9.5Hz...

Embodiment 3

[0051] Embodiment 3. Mannose derivative cationic liposome di -C 16 - Preparation of Man-TMA nanoparticles:

[0052] Add 3'-azidopropyl 4,6- O -Benzylidene-α-D-mannopyranoside (1.6g, 4.6mmol), then dissolved in DMF (60.0mL), then added NaH (1.1g, 27.6mmol) and hexadecane bromide (5.6mL ,18.4mmol). Stirring reaction at room temperature, TLC (V 石油醚 :V 乙酸乙酯 =15:1) Monitor the reaction until there is no significant change. DCM (20.0 mL) was added to the reaction mixture solution, washed with water three times, and the organic phase was washed with anhydrous Na 2 SO 4 Dry, filter and concentrate. Through column chromatography (eluent: V 石油醚 :V 乙酸乙酯 =40:1) separation and purification to obtain white solid compound 3'-azidopropyl 2,3-di- O -n-hexadecyl-4,6- O - Benzylidene-α-D-mannopyranoside (2.0 g, 54.1%). 1 HNMR (500MHz, CDCl 3 ): δ(ppm)7.51-7.33(m,5H,C 6 H 5 ),5.60(s,1H,C 6 h 5 C H ),4.81(d,1H, J 1,2 =1.5Hz,H-1),4.24(dd,1H, J 6a,5 =5.0Hz, J 6a,6b =10.0Hz,...

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Abstract

The present invention discloses a mannose derivative cation liposome nanoparticle preparation method. According to the present invention, mannose is adopted as a raw material to synthesize a series of mannose derivative cation lipids with different structures, and the liposomes are dispersed with water to obtain a series of the mannose derivative cation liposome nanoparticles with characteristics of good structure stability, moderate particle size, narrow particle size distribution, moderate surface charge and low production cost, wherein the lipids comprise di-C12-Man-TMA, di-C14-Man-TMA, di-C16-Man-TMA, di-C18-Man-TMA, Man-DiC12MA, Man-DiC14MA, Man-DiC16MA and Man-DiC18MA; and with the mannose derivative cation liposome nanoparticles, the transport of the nucleic acid drug from the extra-cell to the intra-cell can be achieved, and the mannose derivative cation liposome nanoparticles can be used as the transport vector of the non-nucleic acid drug.

Description

technical field [0001] The invention relates to a preparation method of a series of mannose derivative cationic liposome nanoparticles. Background technique [0002] Human gene therapy has gradually become one of the main directions of modern medical development. The ultimate goal of gene therapy is to express foreign genes efficiently in a suitable system. In the process of introducing exogenous genes into cells, DNA will be degraded by nucleases in the body, and will be degraded into small molecular nucleotides before entering the target cells or even reaching the target organs, thus losing the therapeutic effect. In order to better protect the therapeutic gene during in vivo transportation, it can be combined with a gene carrier. Therefore, the development of gene carriers is particularly important for the development of gene therapy. Commonly used gene carriers include viral vectors and non-viral vectors. Viral vectors have high transduction efficiency, the complex as...

Claims

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Application Information

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IPC IPC(8): C07H15/04C07H1/00A61K47/26A61K9/127A61K48/00
Inventor 曾佑林刘美艳邓亮亮
Owner HUNAN NORMAL UNIVERSITY