Functional single-chain cyclic poly (beta-amino ester) as well as preparation method and gene delivery drug application thereof

A functional, aminoester technology, applied in the field of functional single-chain cyclic polymer and its preparation, gene delivery drug application field, can solve the problems of no way, limited clinical approval and large-scale application, achieve narrow PDI, charge The effect of easy adjustment of density and composition, good biocompatibility

Active Publication Date: 2022-01-14
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is almost no way to separate poly(β-amino ester) HPAE with the same components and different molecular weights, which greatly limits its clinical approval and large-scale application.

Method used

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  • Functional single-chain cyclic poly (beta-amino ester) as well as preparation method and gene delivery drug application thereof
  • Functional single-chain cyclic poly (beta-amino ester) as well as preparation method and gene delivery drug application thereof
  • Functional single-chain cyclic poly (beta-amino ester) as well as preparation method and gene delivery drug application thereof

Examples

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preparation example Construction

[0038] A synthetic method of a class of functional single-chain cyclic poly(β-amino ester) disclosed by the present invention, the synthetic route can be found in figure 1 , including the following steps:

[0039]1) A linear poly(β-amino ester) with a double bond is obtained through a Michael addition reaction between a diacrylate monomer and a small molecule organic amine;

[0040] 2) The linear poly(β-amino ester) with double bond prepared in step 1) is subjected to reversible addition-fragmentation chain transfer polymerization to obtain a single-chain polycyclic poly(β-amino ester) with controllable structure and composition ;

[0041] 3) Adding a functional end-capping agent to the single-chain polycyclic poly(β-amino ester) prepared in step 2) for functional end-capping treatment to prepare a functional single-chain cyclic poly(β-amino ester).

[0042] Specifically, the following steps are included:

[0043] 1) Add a certain amount of diacrylate monomer and small mole...

Embodiment 1

[0064] The reaction ratio of 2,2-dithiodiethanol diacrylate and dodecylamine is 2:1, react at 60°C for 5h; add 0.5 equivalent of 2,2-dithiodiethanol diacrylate, After 48 hours of reaction, the obtained low molecular weight linear poly(β-amino ester) had a molecular weight of 3000 Da.

[0065] Low molecular weight linear poly(β-amino ester), chain transfer agent and AIBN reaction feed ratio is 300:1:1, react at 50°C for 50h, then add 4 equivalents of N-(2-aminoethyl)morpholine, After reacting at 25°C for 48 hours, the obtained single-chain polycyclic poly(β-amino ester) had a molecular weight of 30,000 Da.

[0066] figure 2 It is a solution state in which the single-chain polycyclic poly(β-amino ester) with a molecular weight of 30,000 Da prepared in this example is dissolved in dimethyl sulfoxide. image 3 The H NMR spectrum of the single-chain polycyclic poly(β-amino ester) with a molecular weight of 30,000 Da prepared for this example.

[0067] see Figure 4 , Figure ...

Embodiment 2

[0069] The reaction ratio of bisphenol A polyoxyethylene ether diacrylate and dodecylamine is 0.5:1, react at 60°C for 2h; add 1 equivalent of bisphenol A polyoxyethylene ether diacrylate, react at 25°C for 48h , to obtain a linear poly(β-amino ester) with a molecular weight of 2800 Da.

[0070] Low molecular weight linear poly(β-amino ester), chain transfer agent and AIBN reaction ratio is 200:5:1, react at 50℃ for 96h, then add 5 equivalents of 1,11-diamino-3,6,9 - Trioxaundecane, reacted at 25° C. for 48 hours, and the molecular weight of the obtained single-chain polycyclic poly(β-amino ester) was 40000 Da.

[0071] see Figure 4 , Figure 4 (b) is the purified gel permeation chromatography (GPC) curve of the single-chain polycyclic poly(β-amino ester) with a molecular weight of about 40,000 Da prepared in this example.

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Abstract

The invention discloses functional single-chain cyclic poly (beta-amino ester) as well as a preparation method and gene delivery drug application thereof, and belongs to the technical field of biomedical materials. The functional poly (beta-amino ester) with a multi-ring structure, which is brand new in structure, can be prepared by changing the composition and proportion of linear oligomers (beta-amino ester) in a main chain, polymer molecular weight and cyclization degree, and linear poly (beta-amino ester) with low molecular weight and narrower PDI is prepared by diacrylate and small molecular amine through a Michael addition strategy. Then, RAFT polymerization reaction is carried out on the product by using a one-pot method to prepare the single-chain polycyclic poly (beta-amino ester) with narrower PDI. The preparation method is simple and efficient, the used raw materials are cheap and easy to obtain, and the production cost is well reduced. The polymer has the advantages that: the charge density and composition of the polymer are easy to adjust, the polymer is biodegradable, and the polymer has good biocompatibility, can be widely applied to delivery of DNA or RNA, and has potential clinical application potential.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and relates to a class of functional single-chain cyclic poly(β-amino ester) and its preparation method and application of gene delivery medicine. Background technique [0002] Gene therapy refers to the use of certain methods to deliver genetic materials such as DNA or RNA with specific functions into targeted tissue cells to replace diseased genes or inhibit the expression of diseased genes. Dystrotrophic epidermolysis bullous, etc.) or acquired diseases (such as Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, etc.) are one of the most promising treatments. But at present, the lack of safe and effective non-viral gene vectors greatly limits the clinical application of gene therapy. [0003] As one of the most representative non-viral gene carriers, cationic polymer carriers have been reported extensively. At present, commonly used cationic polymers such as polyethyleneimine...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G73/00A61K47/34A61K48/00
CPCC08G73/00A61K47/34A61K48/0041A61K48/005
Inventor 周德重王晨飞孙力涛李秋霞李建忠耿松梅车德路郭坤
Owner XI AN JIAOTONG UNIV
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