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Biodegradable polymer, preparation method thereof and nucleic acid drug delivery carrier

A polymer and synthesis method technology, applied in the field of life medicine, can solve the problems of toxicity, immune stimulation, and low transfection efficiency, and achieve good stability, high reproducibility, and simple preparation methods

Inactive Publication Date: 2012-11-21
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some breakthroughs and progress have been made in the carrier research of nucleic acid drugs, there are still some key issues to be solved in order to make nucleic acid drugs successfully applied in vivo and become a routine way, such as: toxicity, specificity, targeting , immune stimulation, low transfection efficiency, etc.

Method used

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  • Biodegradable polymer, preparation method thereof and nucleic acid drug delivery carrier
  • Biodegradable polymer, preparation method thereof and nucleic acid drug delivery carrier
  • Biodegradable polymer, preparation method thereof and nucleic acid drug delivery carrier

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preparation example Construction

[0049]3. Preparation and Stability Test of Compound Nanoparticles of Formula I

[0050] The amphiphilic copolymer can be prepared into nanoparticles in aqueous solution by conventional methods, such as solvent evaporation and dialysis.

[0051] Solvent evaporation method: Dissolve the copolymer in tetrahydrofuran, add ultrapure water dropwise under stirring to obtain the corresponding final concentration, after stirring for two hours, remove the organic solvent under reduced pressure, and then set the volume to a suitable volume.

[0052] Dialysis method: Dissolve the copolymer in a good solvent such as dimethyl sulfoxide (DMSO), and drop into ultrapure water under stirring to obtain the corresponding final concentration. After stirring for two hours, dialyze in a dialysis bag to remove the organic solvent.

[0053] The nanoparticles of each carrier material provided by the invention are prepared by a solvent volatilization method, and the particle size distribution and surfac...

Embodiment 1

[0068] Embodiment 1, the synthesis of single / double hydroxyl polyhydroxyalkanoate and its end group modification

[0069] a. Synthesis and characterization of mono / dihydroxy polyhydroxyalkanoate (mPHA-OH / PHA-diol)

[0070] The synthesis of various mono / dihydroxy polyhydroxyalkanoate (mPHA-OH / PHA-diol) is prepared by transesterification reaction with methanol or diol under the catalysis of p-toluenesulfonic acid (PTSA). The alcohol may be ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol. All kinds of polyhydroxyalkanoate raw materials in the present invention are purchased from Shenzhen Ecoman Biotechnology Co., Ltd. The operation steps of this type of reaction are illustrated below by taking monomethyl poly-3-hydroxybutyrate-4-hydroxybutyrate (mP3 / 4HB-OH) and polyhydroxybutyrate diol (PHB-diol) as examples.

[0071] The synthetic route of mP3 / 4HB-OH is as follows figure 1 (A) shown. mP3 / 4HB-OH is prepared by transesterification of P3 / 4HB and methanol under ...

Embodiment 2

[0081] Embodiment 2, synthesis and characterization of polyhydroxyalkanoate and cationic compound copolymer

[0082] Copolymers of polyhydroxyalkanoates of different types and molecular weights with cationic peptides, cationic lipids, and cationic polymers are based on mono / dihydroxy, mono / dicarboxy, mono / dipropenyl groups of corresponding types and molecular weights. Polyhydroxyalkanoates and cationic peptides, cationic esters, and cationic polymers, with HDI / CDI / IPDI / DCC / EDC as linkers or condensation agents, in stannous octoate (Sn(Oct) 2 ) or 4-dimethylaminopyridine (DMAP) under the catalysis of solution polymerization, condensation or Michael addition and other methods; by adjusting the molecular weight of polyhydroxyalkanoate and cationic compound and the ratio of the two can get different molecular weight , Copolymers of different compositions. Due to its high catalytic activity and non-toxicity, stannous octoate is the most widely used polymerization catalyst and has ...

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Abstract

The invention discloses a biodegradable polymer and a preparation method thereof. The biodegradable polymer is a polymer formed by copolymerization of polyhydroxyalkanoates and cation compounds, and has a general structural formula I: [A; B / L], wherein A is polyhydroxyalkanoates, B is one of the cation compounds and L is a linker part; and the cation compounds are cation peptide, cation ester andcation polymer. The invention also discloses a nucleic acid drug delivery carrier which is nanoparticles with positive charges of which the active component is the biodegradable polymer, wherein the particle size of the nanoparticles is 30-600nm and the zeta potential of the nanoparticles is 2-60mV. The polymer disclosed by the invention has the advantages of biodegradability, biocompatibility, relative hydrophobicity, cheap raw materials, cost saving and the like, and due to the relative hydrophobicity, self assembly of the copolymer is promoted by the hydrophilic-hydrophobic interaction among polymer chains.

Description

technical field [0001] The invention relates to a biodegradable polymer, a preparation method thereof and a related nucleic acid drug delivery carrier, belonging to the field of life medicine. Background technique [0002] Due to their unique high efficiency and specificity, nucleic acid drugs have gradually been developed into new gene therapy methods for the treatment of hereditary or acquired diseases, including viral infection and cancer. In addition, they also play an important role in the study of gene function. important role. However, due to the huge molecular weight of nucleic acid drugs and the large amount of negative charges they carry, they cannot autonomously cross the cell membrane and enter the cells to play a role, and they are prone to non-specific off-target effects and immune responses when transported in the system. At the same time, they also face degradation by nucleases, etc. Therefore, the transfection problem of nucleic acid drugs has become the ma...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G63/91C08G81/00A61K47/34A61K48/00
Inventor 张必良周丽
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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