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Amphiphilic triblock copolymer, polymer nano-carrier preparation and preparation methods

A nano-carrier and tri-block technology, applied in the field of nano-medicine, can solve the problem that small-molecule drugs, genes and proteins cannot be loaded at the same time

Active Publication Date: 2013-10-30
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, traditional nanocarriers generally can only load one component, and cannot simultaneously load small molecule drugs, genes, and proteins.

Method used

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  • Amphiphilic triblock copolymer, polymer nano-carrier preparation and preparation methods
  • Amphiphilic triblock copolymer, polymer nano-carrier preparation and preparation methods
  • Amphiphilic triblock copolymer, polymer nano-carrier preparation and preparation methods

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preparation example Construction

[0067] This embodiment also provides a method for preparing an amphiphilic triblock copolymer, comprising the following steps:

[0068] Step S110: Using polyethylene glycol derivatives as initiators, synthesizing linear triblock copolymers comprising polyethylene glycol derivatives, side chain-protected polylysine and polyleucine by NCA ring-opening polymerization , wherein one end of the side chain-protected polylysine is connected to polyethylene glycol derivatives through an amide bond, and the other end is connected to polyleucine through a peptide bond, and the molecular weight of the polyethylene glycol derivatives is in the range of 500-10000 , the degree of polymerization of polylysine with side chain protection is 10-200, and the degree of polymerization of polyleucine is 10-200.

[0069] The details are as follows: dissolve polyethylene glycol derivatives with a molecular weight range of 500-10000 in an organic solvent at a concentration range of 1-100 mg / mL, heat to...

example 1

[0107] Example 1, the preparation of polyethylene glycol monomethyl ether-polylysine-polyleucine triblock copolymer

[0108] The polymerization tube was evacuated and then filled with nitrogen protection, and 1 g of CH with a molecular weight of 500 3 O-PEG-NH 2 Dissolve it with 20mL DMF and add it into the polymerization tube, press LysZ-NCA monomer and CH 3 O-PEG-NH 2 The molar ratio of the LysZ-NCA monomer was added in a ratio of 10:1, and the constant temperature reaction was carried out under nitrogen protection for 24 hours, and then the Leu-NCA monomer and CH 3 O-PEG-NH 2 Add the Leu-NCA monomer with a molar ratio of 10:1, and continue to react at a constant temperature for 24 hours under the protection of nitrogen. After the reaction, add ether 50 times the volume of the reaction system to precipitate, filter, and dry to obtain PEG-PLysZ-PLeu three-block segment copolymers.

[0109] Dissolve the PEG-PLysZ-PLeu polymer obtained above in trifluoroacetic acid at 0°C,...

example 2

[0110] Example 2, the preparation of carboxypolyethylene glycol-polylysine-polyleucine triblock copolymer

[0111] After the polymerization tube was evacuated, it was filled with nitrogen protection, and 0.5g of NH with a molecular weight of 2000 2 -PEG-COOH was dissolved in 20mL of DMF and added to the polymerization tube, according to the LysZ-NCA monomer and CH 3 O-PEG-NH 2 The molar ratio of the LysZ-NCA monomer was added in a ratio of 20:1, and the constant temperature reaction was carried out under nitrogen protection for 24 hours, and then the Leu-NCA monomer and CH 3 O-PEG-NH 2 Add the Leu-NCA monomer at a molar ratio of 40:1, and continue the constant temperature reaction for 48 hours under nitrogen and protection. After the reaction, add 20 times the volume of ether in the reaction system to precipitate, filter, and dry to obtain PEG-PLysZ-PLeu3 block copolymers.

[0112] Dissolve the PEG-PLysZ-PLeu polymer obtained above in trifluoroacetic acid at 0°C, add a HBr...

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Abstract

The invention relates to an amphiphilic triblock copolymer, a polymer nano-carrier preparation and preparation methods. The copolymer is a liner polymer compound containing a polyethylene glycol derivative, poly-lysine and poly-leucine, wherein one end of the poly-lysine is connected with the polyethylene glycol derivative through an amide bond, and the other end of the poly-lysine is connected with the poly-leucine through a peptide bond. The amphiphilic triblock copolymer, namely the polyethylene glycol derivative-poly-lysine-poly-leucine triblock copolymer combines the advantages of polyethylene glycol and poly-amino acid, can form a nano-carrier with a three-layer structure by self-assembly in a water solution, and can simultaneously effectively load a small molecular hydrophobic medicament, gene substances and proteins or polypeptides to form a multifunctional nano-carrier.

Description

【Technical field】 [0001] The invention relates to the field of nanomedicine, in particular to an amphiphilic triblock copolymer, a polymer nanocarrier preparation and a corresponding preparation method. 【Background technique】 [0002] Nanocarriers refer to nanoscale systems that can carry target substances such as small molecule drugs, genes, and proteins. [0003] Nano-drug carriers refer to nano-systems that can load drugs, and are mainly used for slow-release, controlled-release, targeted delivery of drugs, and increasing the solubility of hydrophobic drugs. Polymer nanomicelle is the most studied nano drug carrier, which is prepared by self-assembly of amphiphilic (having both hydrophilic and lipophilic components) polymer molecules in aqueous solution, with a hydrophobic core and a hydrophilic sex shell. Polymer nanomicelles have a lower minimum micelle-forming concentration (CMC) than conventional small-molecule micelles, so they can efficiently and stably load hydro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G69/40A61K47/34A61K9/19A61K9/08A61K48/00A61P35/00
Inventor 蔡林涛邓吉喆马轶凡王亚楠易虎强郑翠芳
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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