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A kind of shedding polymer nanocarrier, its preparation method and application

A nanocarrier and polymer technology, applied in the field of nanomedicine, can solve the problems of not being able to have active targeted delivery at the same time, not being able to be completely degraded or metabolized, not being able to control particle size and potential, etc., to achieve good market prospects and avoid immune system. Clearing, drug-stabilizing effect

Active Publication Date: 2015-11-11
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a polymer nanocarrier with a detachable shell, which aims to solve the problem that the existing nanocarriers have poor stability, cannot be completely degraded or metabolized, and cannot simultaneously have functions such as active targeted delivery, pH response and reduction responsiveness. , and the problem that its particle size and potential cannot be adjusted
[0007] Another object of the present invention is to provide a nano-carrier drug with a detachable shell, which aims to solve the problem that the existing nano-carrier drug has poor stability, cannot be completely degraded or metabolized, and cannot have active targeted delivery, pH response and reduction response at the same time Sexuality and other functions, as well as the problem that its particle size and potential cannot be adjusted

Method used

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  • A kind of shedding polymer nanocarrier, its preparation method and application
  • A kind of shedding polymer nanocarrier, its preparation method and application
  • A kind of shedding polymer nanocarrier, its preparation method and application

Examples

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preparation example Construction

[0054] Correspondingly, an embodiment of the present invention provides a method for preparing a shell-shedding polymer nanocarrier, comprising the following steps:

[0055] S01. Synthesis of TP-PEG-b-PLL (DMMA)-capping agent diblock polymer: by HOOC-PEG-NH 2 React with Lys(Boc)-NCA to obtain PEG-b-PLL(Boc); Use a capping agent to block the amino group at the end of PLL(Boc) to obtain PEG-b-PLL(Boc)-capping agent; Activate PEG-b-PLL (Boc)-The PEG carboxyl end of the capping agent is combined with TP to obtain the TP-PEG-b-PLL(Boc)-capping agent; the Boc protecting group is removed from the TP-PEG-b-PLL(Boc)-capping agent After grouping, react with 2,3-dimethylmaleic anhydride to obtain TP-PEG-b-PLL (DMMA)-blocking agent diblock polymer;

[0056] S02. Synthesis of Initiator-PLL-b-PLC Diblock Polymer: Reaction of Initiator with Lys(Boc)-NCA to Obtain Initiator-PLL(Boc), Reaction with Cys(Trt)-NCA to Obtain Initiator -PLL(Boc)-b-PLC(Trt) two-block polymer; remove the protecting...

Embodiment 1

[0096] The synthesis of embodiment 1TP-PEG-b-PLL (DMMA)-HPPr diblock polymer

[0097] S111 Vacuumize the polymerization tube and fill it with nitrogen for protection. Add 1g of HOOC-PEG-NH with a molecular weight of 500KD 2 Dissolve it with 40mL DMF and add it into the polymerization tube, mix Lys(Boc)-NCA monomer with HOOC-PEG-NH 2 Lys(Boc)-NCA monomer was added at a molar ratio of 10:1, and reacted at a constant temperature for 24 hours under nitrogen protection. After the reaction, 10 times of ether was added to precipitate, filtered, and dried to obtain PEG-b-PLL(Boc) block polymers.

[0098] S112 Add the PEG-b-PLL (Boc) diblock polymer obtained above to 3 times the molar amount of succinimide phenylpropionate and dissolve it in 30 mL of DMF, then add it to a round-bottomed flask and stir overnight at room temperature (25°C). After the reaction, add 20 times of diethyl ether to precipitate, filter and dry to obtain PEG-b-PLL(Boc)-HPPr diblock polymer.

[0099] S113 Add ...

Embodiment 2

[0102] The synthesis of embodiment 2TP-PEG-b-PLL (DMMA)-HPPr diblock polymer

[0103] S211 Vacuumize the polymerization tube and fill it with nitrogen for protection, and put 2g of HOOC-PEG-NH with a number average molecular weight of 5000KD 2 Dissolve with 400mL DMF and add to the polymerization tube, mix Lys(Boc)-NCA monomer with HOOC-PEG-NH 2 Lys(Boc)-NCA monomer was added at a molar ratio of 5:1, and reacted at a constant temperature for 12 hours under nitrogen protection. After the reaction, 25 times of diethyl ether was added to precipitate, filter, and dry to obtain PEG-b-PLL(Boc). block polymers.

[0104] S212 Add the PEG-b-PLL (Boc) diblock polymer obtained above to 5 times the molar amount of succinimide phenylpropionate and dissolve it in 50 mL of DMF, then add it to a round-bottomed flask and stir overnight at room temperature (25°C) for reaction. After the reaction, add 40 times of diethyl ether to precipitate, filter and dry to obtain PEG-b-PLL(Boc)-HPPr dibloc...

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Abstract

The invention is applicable to the field of nano medicine, and provides a shell-droppable polymer nano carrier as well as a preparation method and an application thereof. The shell-droppable polymer nano carrier comprises two diblock polymers: a TP-PEG-b-PLL (DMMA)-end capping agent and an initiator-PLL-b-PLC; the two diblock polymers are combined into a core-shell structure through electrostatic adsorption; the core-shell structure is divided into four layers sequentially from outside to inside; and the weight ratio of the TP-PEG-b-PLL (DMMA)-end capping agent to the initiator-PLL-b-PLC is (1-100):(1-100). The shell-droppable polymer nano carrier preparation can be completely biodegraded and also has the functions of active targeting transfer, pH response and reduction response; and the particle size and electric potential can be controlled.

Description

technical field [0001] The invention belongs to the field of nanomedicine, and in particular relates to a shell-shedding polymer nanocarrier, a preparation method and application thereof. Background technique [0002] With the development of nanobiotechnology, multifunctional intelligent polymer nanoparticles have attracted more and more attention, especially in the field of cancer cell therapy. As a new type of drug carrier, multifunctional intelligent nanocarriers have been widely used in targeted delivery. Pharmaceutical field, and has good development prospects. After smart nanocarriers selectively deliver drugs to specific targets, they can release loaded drugs responsively after being stimulated by chemical signals or "triggers" such as temperature or pH. This kind of nanocarriers can be divided into active targeted delivery system and passive targeted delivery system. [0003] The nano-passive targeted delivery system refers to the targeting of the nano-carriers to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K9/51A61P35/00C08G69/48C08G69/40A61K31/704A61K31/337A61K31/4745
Inventor 蔡林涛易虎强刘朋马轶凡谢高峰
Owner SHENZHEN INST OF ADVANCED TECH
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