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Cystoid type spherical nucleic acid and preparation method and application thereof

A spherical and vesicle technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of not being able to carry chemical drugs and/or protein drugs at the same time, and achieve the goal of carrying High drug efficiency, simple process, and intracellular reduction-sensitive effect

Active Publication Date: 2018-11-06
HENAN UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the spherical nucleic acid in the related art can only be used to deliver nucleic acid drugs, and cannot carry chemical drugs and / or protein drugs at the same time. How to effectively deliver nucleic acid drugs and chemical drugs and / or protein drugs at the same time is currently impossible for spherical nucleic acids. solved problem

Method used

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  • Cystoid type spherical nucleic acid and preparation method and application thereof
  • Cystoid type spherical nucleic acid and preparation method and application thereof
  • Cystoid type spherical nucleic acid and preparation method and application thereof

Examples

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preparation example Construction

[0064] A method for preparing vesicular spherical nucleic acid, comprising:

[0065] The PNIPAM-S-S-Py polymer is reacted with functionalized nucleic acid drugs to obtain a diblock complex capable of forming vesicular spherical nucleic acids.

[0066] The vesicular spherical nucleic acid of the present invention adopts PNIPAM-S-S-Py polymer to react with functionalized nucleic acid drug to obtain a diblock complex, and the diblock complex can be formed by self-assembly under the condition higher than the critical transition temperature LCST The vesicle-shaped spherical nucleic acid has a simple process and is suitable for large-scale production.

[0067] In a preferred embodiment of the present invention, the reaction of the PNIPAM-S-S-Py polymer with a functionalized nucleic acid drug to obtain a diblock complex includes:

[0068] The PNIPAM-S-S-Py polymer and the functionalized nucleic acid drug are reacted in a solvent to obtain a diblock complex.

[0069] The present inv...

Embodiment 1-3

[0112] A method for preparing vesicular spherical nucleic acid, comprising:

[0113] 1. NIPAM forms PNIPAM polymer through RAFT polymerization:

[0114] 1.1 NIPAM (isopropylacrylamide) (sigma) monomer, RAFT (Reversible Addition-Fragmentation Chain Transfer Polymerization) reagent (Bailingwei Technology), initiator AIBN (azobisisobutyronitrile) (Aladdin) Polymerization takes place at specific ratios (80:1:0.1, 150:1:0.2 and 200:1:0.3 respectively in Examples 1-3) (reaction temperatures in Examples 1-3 are respectively 65 ℃, 75 ℃ and 70 ℃, the reaction time of embodiment 1-3 is respectively 36h, 12h and 24h successively) generates PNIPAM polymer (the molecular weight Mn of embodiment 1-3 gained PNIPAM polymer is about 7000, 13000 respectively successively , 19000, respectively recorded as 7k, 13k and 19k).

[0115] Take the 19K polymer synthesis process as an example:

[0116] Prepare a 25mL or 50mL reaction tube, and first pass N through the double row tube 2 Purify for 30 ...

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Abstract

The invention provides a cystoid type spherical nucleic acid and a preparation method and application thereof. The cystoid type spherical nucleic acid adopts a PNIPAM-S-S-Py polymer to react with functionalized nucleic acid drugs to obtain a diblock compound, the technology is simple, and the technology is applicable to large-scale production. The cystoid type spherical nucleic acid is of a specific cystoid structure, is high in stability, high in uniformity, high in biocompatibility, tumor targeting and reductive sensitivity inside cells, is degradable, and can be used for efficiently delivering the nucleic acid drugs to specific target cells. The cystoid type spherical nucleic acid can be used as a drug carrier and is high in drug-carrying efficiency, nucleic acid drugs and other drugs can be delivered effectively synchronously, and the cystoid type spherical nucleic acid is of a synergy therapy effect.

Description

technical field [0001] The present invention relates to the technical field of nucleic acid medicines, in particular to a vesicular spherical nucleic acid and its preparation method and application. Background technique [0002] Nucleic acid drugs are various oligoribonucleotides (RNA) or oligodeoxyribonucleotides (DNA) with different functions, which mainly play a role at the gene level. It shows good application potential in the treatment of diseases. [0003] However, nucleic acid drugs will be easily affected and eliminated by human cells after entering the human body, and cannot achieve the expected effect. Taking siRNA as an example, naked siRNA itself has problems such as electronegativity, large molecular weight, strong polarity, short half-life, and is easily degraded by endogenous enzymes and glomerular filtration. After siRNA enters the organism, it is easily absorbed by blood or cells siRNA that enters the body is easily captured by the reticulo endothelial sys...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/58A61K31/7088A61K45/06
CPCA61K9/1273A61K31/7088A61K45/06A61K47/58A61K2300/00
Inventor 师冰洋郑蒙邹艳江通
Owner HENAN UNIVERSITY
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